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Stocker H, Beyer L, Trares K, Stevenson-Hoare J, Rujescu D, Holleczek B, Beyreuther K, Schoettker B, Gerwert K, Brenner H. Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study. Neurology 2025; 104:e213500. [PMID: 40239154 PMCID: PMC12006662 DOI: 10.1212/wnl.0000000000213500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 03/06/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Dementia-related blood biomarkers are the future of large-scale dementia risk stratification; however, the extent to which phosphorylated tau (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are associated with nonmodifiable risk factors has yet to be confirmed in the community, and the role of menopause has yet to be investigated. Therefore, the aim of this study was to examine the association of age, sex, APOEe4 status, and menopause, with dementia-related blood biomarker levels (P-tau181, NfL, and GFAP) and rate of change over 11 years in longitudinal biomarker measurements in community-dwelling adults. METHODS Within this German population-based Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung cohort study (n = 9,940), a nested case-control study of 1,026 participants (1:1, without dementia during follow-up: incident dementia during follow-up) aged 50-75 years at baseline followed over 17 years was conducted. Blood biomarker measurements (P-tau181, NfL, and GFAP) were completed in blood from baseline, 8-year, and 11-year follow-ups, and cross-sectional and longitudinal regression analyses were used to assess the association with age, sex, APOEe4, and menopause. RESULTS The mean age of participants was 64 years, and women accounted for slightly over half (54%) of the sample. Age was cross-sectionally and longitudinally significantly associated with all dementia-related biomarkers (p < 0.001). NfL and GFAP levels more strongly correlated (Spearman R = 0.55 and 0.49) with age at baseline than P-tau181 levels (Spearman R = 0.21). Women experienced significantly higher levels and rates of increase in GFAP (p < 0.001) while men experienced higher levels of NfL after adjusting for age and APOEe4 (p < 0.01). APOEe4 status was significantly associated with baseline and longitudinal levels of P-tau181 (baseline β = 0.30, p < 0.05) and GFAP (baseline β = 15.84, p < 0.001). Of interest, premenopausal status was significantly associated with higher GFAP levels after adjusting for age, sex, and APOEe4 (β = 19.09, p < 0.05). DISCUSSION This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants. Future research should confirm these findings and further explore the role of menopause in dementia pathogenesis among women.
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Affiliation(s)
- Hannah Stocker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Léon Beyer
- Center for Protein Diagnostics (ProDi), Ruhr-University Bochum, Germany
- Department of Biophysics, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Germany
| | - Kira Trares
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Joshua Stevenson-Hoare
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Dan Rujescu
- Department of Psychiatry, Medical University of Vienna, Austria
| | | | | | - Ben Schoettker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Klaus Gerwert
- Center for Protein Diagnostics (ProDi), Ruhr-University Bochum, Germany
- Department of Biophysics, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
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Rahmani F, Khanjani MS, Azkhosh M, Younesi SJ, Hassani-Abharian P, Hoseinzadeh S, Sayadnasiri M. Development of a 12-Word Version of a Verbal Learning Test for Persian-Speaking Older Adults: Reliability, Construct Validity, and Normative Standards. Arch Clin Neuropsychol 2025; 40:498-509. [PMID: 38720555 DOI: 10.1093/arclin/acae037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 03/23/2024] [Accepted: 04/26/2024] [Indexed: 04/29/2025] Open
Abstract
OBJECTIVE As people enter old age, they develop diseases, challenges, and cognitive and behavioral deficits that are associated with decreased abilities. Memory abilities and deficiencies and impaired models can be assessed using neuropsychological instruments, and a rehabilitation program can be developed based on the individuals' memory deficits. The present cross-sectional research aims to develop a new test (henceforth known as the Persian Verbal Learning Test, or PVLT) that is appropriate for Persian-speaking older adults. METHODS For normative data, we administered PVLT to a group of 374 Persian-speaking healthy older adults consisting of both genders (190 women and 184 men) who were aged 60-89 years old. To determine reliability and validity, we evaluated neurologically healthy older adults and analyzed the results using intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. RESULTS The present findings showed that age, education, and gender significantly affect subtests of the PVLT. In the evaluation of reliability, significant positive correlations were observed between the variables of the PVLT in the standard/standard form. Furthermore, moderate correlations were observed between PVLT variables (immediate recall, short-delay recall, long-delay recall, and recognition), and the Immediate and Delayed Logical Memory subtests of Wechsler Memory Scale-Revised (WMS-R). However, subtests of the PVLT also showed significantly positive correlations with MoCA and non-verbal variables of WMS-R. CONCLUSION According to the results of this study and given the good psychometric properties obtained, PVLT can potentially be used as a more appropriate tool than the SVLT for Persian-speaking older adults.
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Affiliation(s)
- Fahimeh Rahmani
- Department of Counseling, School of Behavioral Sciences and Mental Health, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
- Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Mohammad Saeed Khanjani
- Department of Counseling, School of Behavioral Sciences and Mental Health, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
- Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Manoochehr Azkhosh
- Department of Counseling, School of Behavioral Sciences and Mental Health, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Seyyed Jalal Younesi
- Department of Counseling, School of Behavioral Sciences and Mental Health, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | | | - Samaneh Hoseinzadeh
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sayadnasiri
- Department of Psychiatry, School of Behavioral Sciences and Mental Health, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
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Chen L, Tian X, Wu J, Lao G, Zhang Y, Wei H. COLLATOR: Consistent spatial-temporal longitudinal atlas construction via implicit neural representation. Med Image Anal 2025; 100:103396. [PMID: 39642701 DOI: 10.1016/j.media.2024.103396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/27/2024] [Accepted: 11/15/2024] [Indexed: 12/09/2024]
Abstract
Longitudinal brain atlases that present brain development trend along time, are essential tools for brain development studies. However, conventional methods construct these atlases by independently averaging brain images from different individuals at discrete time points. This approach could introduce temporal inconsistencies due to variations in ontogenetic trends among samples, potentially affecting accuracy of brain developmental characteristic analysis. In this paper, we propose an implicit neural representation (INR)-based framework to improve the temporal consistency in longitudinal atlases. We treat temporal inconsistency as a 4-dimensional (4D) image denoising task, where the data consists of 3D spatial information and 1D temporal progression. We formulate the longitudinal atlas as an implicit function of the spatial-temporal coordinates, allowing structural inconsistency over the time to be considered as 3D image noise along age. Inspired by recent self-supervised denoising methods (e.g. Noise2Noise), our approach learns the noise-free and temporally continuous implicit function from inconsistent longitudinal atlas data. Finally, the time-consistent longitudinal brain atlas can be reconstructed by evaluating the denoised 4D INR function at critical brain developing time points. We evaluate our approach on three longitudinal brain atlases of different MRI modalities, demonstrating that our method significantly improves temporal consistency while accurately preserving brain structures. Additionally, the continuous functions generated by our method enable the creation of 4D atlases with higher spatial and temporal resolution. Code: https://github.com/maopaom/COLLATOR.
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Affiliation(s)
- Lixuan Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xuanyu Tian
- School of Information Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Jiangjie Wu
- School of Information Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Guoyan Lao
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yuyao Zhang
- School of Information Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Hongjiang Wei
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National Engineering Research Center of Advanced Magnetic Resonance Technologies for Diagnosis and Therapy (NERC-AMRT), Shanghai Jiao Tong University, Shanghai, 200240, China.
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Yousef O, Abbas A, Abdelmeseh M, Qafesha RM, Nabil Y, Elrosasy A, Negida A, Berman BD. Subthalamic nucleus versus globus pallidus internus deep brain stimulation in the treatment of dystonia: A systematic review and meta-analysis of safety and efficacy. J Clin Neurosci 2025; 132:110958. [PMID: 39647323 DOI: 10.1016/j.jocn.2024.110958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/10/2024] [Accepted: 11/28/2024] [Indexed: 12/10/2024]
Abstract
OBJECTIVE This systematic review and meta-analysis aimed to compare the efficacy and safety of deep brain stimulation (DBS) targeting subthalamic nucleus (STN) versus the globus pallidus internus (GPI) in the treatment of dystonia. METHODS A comprehensive search strategy was implemented up to July 2024, across five databases, identifying studies relevant to STN-DBS and GPI-DBS in dystonia. Eligibility criteria included randomized controlled trials (RCTs) and observational studies comparing the two interventions. Two independent reviewers conducted the screening and data extraction. The risk of bias was assessed using RoB-2 for RCTs and the Newcastle-Ottawa Scale for cohort studies. Statistical analysis involved meta-analysis using Review Manager, with heterogeneity assessed by I2 and Chi-square tests. Subgroup and sensitivity analyses were performed. RESULTS Five studies, involving 154 patients, were included. No significant difference was found between STN-DBS and GPI-DBS in Burke-Fahn-Marsden Dystonia Rating Scale motor and disability (BFMDRS-M and BFMDRS-D) scores at 1 months, 6 and 12 months. STN-DBS showed significant improvement in mental health (SMD = 0.43, 95 % CI: [0.05, 0.8], P = 0.03). STN-DBS also showed significant improvement in Hamilton Anxiety Rating Scale (HAMA) (SMD = -2.7, 95 % CI: [-5.38, -0.02], P = 0.05). No significant difference was found in Hamilton Depression Rating Scale (HAMD) scores. CONCLUSIONS Both STN-DBS and GPI-DBS can improve motor symptoms in dystonia, with STN-DBS potentially resulting in more superior mental health benefits. Future research should address long-term outcomes, and regional effectiveness, and include diverse populations to enhance generalizability.
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Affiliation(s)
- Obai Yousef
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Tartous University, Syria.
| | - Abdallah Abbas
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Maickel Abdelmeseh
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ruaa Mustafa Qafesha
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Al-Quds University, Jerusalem, Palestine
| | - Yehia Nabil
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Zagazig University, Egypt
| | - Amr Elrosasy
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Faculty of Medicine, Cairo University, Cairo Egypt
| | - Ahmed Negida
- Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA; Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA
| | - Brian D Berman
- Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA
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Shao X, Shou Q, Felix K, Ojogho B, Jiang X, Gold BT, Herting MM, Goldwaser EL, Kochunov P, Hong E, Pappas I, Braskie M, Kim H, Cen S, Jann K, Wang DJJ. Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions. eLife 2024; 13:RP96155. [PMID: 39495221 PMCID: PMC11534331 DOI: 10.7554/elife.96155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024] Open
Abstract
The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.
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Affiliation(s)
- Xingfeng Shao
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Qinyang Shou
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Kimberly Felix
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Brandon Ojogho
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Xuejuan Jiang
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
- Department of Ophthalmology, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Brian T Gold
- Department of Neuroscience, College of Medicine, University of KentuckyFrankfortUnited States
| | - Megan M Herting
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Eric L Goldwaser
- Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of MedicineBaltimoreUnited States
- Interventional Psychiatry Program, Department of Psychiatry, Weill Cornell MedicineNew YorkUnited States
| | - Peter Kochunov
- Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at HoustonHoustonUnited States
| | - Elliot Hong
- Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at HoustonHoustonUnited States
| | - Ioannis Pappas
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Meredith Braskie
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Hosung Kim
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Steven Cen
- Department of Radiology and Neurology, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Kay Jann
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
| | - Danny JJ Wang
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
- Department of Radiology and Neurology, Keck School of Medicine, University of Southern CaliforniaLos AngelesUnited States
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Li Y, Yu X, Ma Z, Liu Q, Li M, Tian X, Li B, Zhang R, Gu P, Bai F, Luo G, Li M, Sun D. Nuclear Magnetic Resonance Analysis Implicates Sex-Specific Dysregulation of the Blood Lipids in Alzheimer's Disease: A Retrospective Health-Controlled Study. Psychiatry Investig 2024; 21:1211-1220. [PMID: 39610232 PMCID: PMC11611466 DOI: 10.30773/pi.2024.0164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 08/14/2024] [Accepted: 08/29/2024] [Indexed: 11/30/2024] Open
Abstract
OBJECTIVE The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer's disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. METHODS Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. RESULTS Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). CONCLUSION Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.
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Affiliation(s)
- Yanzhe Li
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Xue Yu
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Zhonghui Ma
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Qinghe Liu
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Min Li
- Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, China
| | - Xue Tian
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Baozhu Li
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Ran Zhang
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Pei Gu
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Fengfeng Bai
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Guoshuai Luo
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Meijuan Li
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
| | - Daliang Sun
- Institute of Mental Health, Tianjin Mental Health Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, China
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Chaudhari NN, Imms PE, Chowdhury NF, Gatz M, Trumble BC, Mack WJ, Law EM, Sutherland ML, Sutherland JD, Rowan CJ, Wann LS, Allam AH, Thompson RC, Michalik DE, Miyamoto M, Lombardi G, Cummings DK, Seabright E, Alami S, Garcia AR, Rodriguez DE, Gutierrez RQ, Copajira AJ, Hooper PL, Buetow KH, Stieglitz J, Gurven MD, Thomas GS, Kaplan HS, Finch CE, Irimia A. Increases in regional brain volume across two native South American male populations. GeroScience 2024; 46:4563-4583. [PMID: 38683289 PMCID: PMC11336037 DOI: 10.1007/s11357-024-01168-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 04/15/2024] [Indexed: 05/01/2024] Open
Abstract
Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46-83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity.
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Affiliation(s)
- Nikhil N Chaudhari
- Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA
| | - Phoebe E Imms
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA
| | - Nahian F Chowdhury
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA
| | - Margaret Gatz
- Center for Economic and Social Research, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA
| | - Benjamin C Trumble
- Center for Evolution & Medicine, School of Human Evolution and Social Change, School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Wendy J Mack
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - E Meng Law
- iBRAIN Research Laboratory, Departments of Neuroscience, Computer Systems and Electrical Engineering, Monash University, Melbourne, VIC, Australia
- Department of Radiology, The Alfred Health Hospital, Melbourne, VIC, Australia
- Department of Neurology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA
| | | | | | - Christopher J Rowan
- Renown Institute for Heart and Vascular Health, Reno, NV, USA
- School of Medicine, University of Nevada, Reno, NV, USA
| | - L Samuel Wann
- Division of Cardiology, University of New Mexico, Albuquerque, NM, USA
| | - Adel H Allam
- Department of Cardiology, School of Medicine, Al-Azhar University, Al Mikhaym Al Daem, Cairo, Egypt
| | - Randall C Thompson
- Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, MO, USA
| | - David E Michalik
- Department of Pediatrics, School of Medicine, University of California, Irvine, Orange, CA, USA
- MemorialCare Miller Children's & Women's Hospital, Long Beach Medical Center, Long Beach, CA, USA
| | - Michael Miyamoto
- Division of Cardiology, Mission Heritage Medical Group, Providence Health, Mission Viejo, CA, USA
| | | | - Daniel K Cummings
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
- Economic Science Institute, Argyros School of Business and Economics, Chapman University, Orange, CA, USA
| | - Edmond Seabright
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
| | - Sarah Alami
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
| | - Angela R Garcia
- Center for Evolution & Medicine, School of Human Evolution and Social Change, School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Daniel E Rodriguez
- Institute of Biomedical Research, San Simon University, Cochabamba, Bolivia
| | | | | | - Paul L Hooper
- Department of Anthropology, University of New Mexico, Albuquerque, NM, USA
| | - Kenneth H Buetow
- Center for Evolution & Medicine, School of Human Evolution and Social Change, School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Jonathan Stieglitz
- Institute for Advanced Study in Toulouse, Toulouse 1 Capitol University, Toulouse, France
| | - Michael D Gurven
- Department of Anthropology, University of California, Santa Barbara, USA
| | - Gregory S Thomas
- MemorialCare Health Systems, Fountain Valley, CA, USA
- Division of Cardiology, University of California, Irvine, Orange, CA, USA
| | - Hillard S Kaplan
- Economic Science Institute, Argyros School of Business and Economics, Chapman University, Orange, CA, USA
| | - Caleb E Finch
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA
- Departments of Biological Sciences, Anthropology and Psychology, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA
| | - Andrei Irimia
- Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
- Department of Quantitative and Computational Biology, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
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8
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Shi Y, Ma J, Li S, Liu C, Liu Y, Chen J, Liu N, Liu S, Huang H. Sex difference in human diseases: mechanistic insights and clinical implications. Signal Transduct Target Ther 2024; 9:238. [PMID: 39256355 PMCID: PMC11387494 DOI: 10.1038/s41392-024-01929-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 06/26/2024] [Accepted: 07/23/2024] [Indexed: 09/12/2024] Open
Abstract
Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.
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Affiliation(s)
- Yuncong Shi
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Jianshuai Ma
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Sijin Li
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Chao Liu
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Yuning Liu
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China
| | - Jie Chen
- Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ningning Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Shiming Liu
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Hui Huang
- Department of Cardiology, the Eighth Affiliated Hospital, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Sun Yat-sen University, Shenzhen, China.
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
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9
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Carpenter JM, Hughes SN, Filipov NM. Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness. Front Neurosci 2024; 18:1465701. [PMID: 39308947 PMCID: PMC11412963 DOI: 10.3389/fnins.2024.1465701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 08/26/2024] [Indexed: 09/25/2024] Open
Abstract
Gulf War Illness (GWI) affects nearly 30% of veterans from the 1990-1991 Gulf War (GW) and is a multi-symptom illness with many neurological effects attributed to in-theater wartime chemical overexposures. Brain-focused studies have revealed persistent structural and functional alterations in veterans with GWI, including reduced volumes, connectivity, and signaling that correlate with poor cognitive and motor performance. GWI symptomology components have been recapitulated in rodent models as behavioral, neurochemical, and neuroinflammatory aberrations. However, preclinical structural imaging studies remain limited. This study aimed to characterize the progression of brain structural alterations over the course of 12 months in two established preclinical models of GWI. In the PB/PM model, male C57BL/6 J mice (8-9 weeks) received daily exposure to the nerve agent prophylactic pyridostigmine bromide (PB) and the pyrethroid insecticide permethrin (PM) for 10 days. In the PB/DEET/CORT/DFP model, mice received daily exposure to PB and the insect repellent DEET (days 1-14) and corticosterone (CORT; days 7-14). On day 15, mice received a single injection of the sarin surrogate diisopropylfluorophosphate (DFP). Using a Varian 7 T Bore MRI System, structural (sagittal T2-weighted) scans were performed at 6-, 9-, and 12-months post GWI exposures. Regions of interest, including total brain, ventricles, cortex, hippocampus, cerebellum, and brainstem were delineated in the open source Aedes Toolbox in MATLAB, followed by brain volumetric and cortical thickness analyses in ImageJ. Limited behavioral testing 1 month after the last MRI was also performed. The results of this study compare similarities and distinctions between these exposure paradigms and aid in the understanding of GWI pathogenesis. Major similarities among the models include relative ventricular enlargement and reductions in hippocampal volumes with age. Key differences in the PB/DEET/CORT/DFP model included reduced brainstem volumes and an early and persistent loss of total brain volume, while the PB/PM model produced reductions in cortical thickness with age. Behaviorally, at 13 months, motor function was largely preserved in both models. However, the GWI mice in the PB/DEET/CORT/DFP model exhibited an elevation in anxiety-like behavior.
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Affiliation(s)
| | | | - Nikolay M. Filipov
- Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
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10
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Sultana OF, Bandaru M, Islam MA, Reddy PH. Unraveling the complexity of human brain: Structure, function in healthy and disease states. Ageing Res Rev 2024; 100:102414. [PMID: 39002647 PMCID: PMC11384519 DOI: 10.1016/j.arr.2024.102414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/29/2024] [Accepted: 07/05/2024] [Indexed: 07/15/2024]
Abstract
The human brain stands as an intricate organ, embodying a nexus of structure, function, development, and diversity. This review delves into the multifaceted landscape of the brain, spanning its anatomical intricacies, diverse functional capacities, dynamic developmental trajectories, and inherent variability across individuals. The dynamic process of brain development, from early embryonic stages to adulthood, highlights the nuanced changes that occur throughout the lifespan. The brain, a remarkably complex organ, is composed of various anatomical regions, each contributing uniquely to its overall functionality. Through an exploration of neuroanatomy, neurophysiology, and electrophysiology, this review elucidates how different brain structures interact to support a wide array of cognitive processes, sensory perception, motor control, and emotional regulation. Moreover, it addresses the impact of age, sex, and ethnic background on brain structure and function, and gender differences profoundly influence the onset, progression, and manifestation of brain disorders shaped by genetic, hormonal, environmental, and social factors. Delving into the complexities of the human brain, it investigates how variations in anatomical configuration correspond to diverse functional capacities across individuals. Furthermore, it examines the impact of neurodegenerative diseases on the structural and functional integrity of the brain. Specifically, our article explores the pathological processes underlying neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, shedding light on the structural alterations and functional impairments that accompany these conditions. We will also explore the current research trends in neurodegenerative diseases and identify the existing gaps in the literature. Overall, this article deepens our understanding of the fundamental principles governing brain structure and function and paves the way for a deeper understanding of individual differences and tailored approaches in neuroscience and clinical practice-additionally, a comprehensive understanding of structural and functional changes that manifest in neurodegenerative diseases.
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Affiliation(s)
- Omme Fatema Sultana
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Madhuri Bandaru
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Md Ariful Islam
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA 5. Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
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11
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Stoisavljevic S, Zdraljevic M, Radojicic A, Pavlovic A, Mijajlovic M. Carotid artery stenosis is related to cerebral small vessel disease magnetic resonance imaging burden. Heliyon 2024; 10:e36052. [PMID: 39224254 PMCID: PMC11367513 DOI: 10.1016/j.heliyon.2024.e36052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 08/05/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024] Open
Abstract
Background Cerebral small vessel disease (CSVD) encompasses conditions that affect small blood vessels of the brain, the most common being atherosclerosis. Magnetic resonance imaging (MRI) CSVD markers include lacunar strokes (LS), white matter hyperintensities (WMH), microbleeds, enlarged perivascular spaces (EPVS), and brain atrophy. Large and small cerebral arteries share an anatomical and functional connection, but the role of large vessel atherosclerosis in atherosclerotic CSVD hasn't been established. The aim of this study was to evaluate the involvement of large vessel pathology in atherosclerotic CSVD. Methods This cross-sectional study included 98 patients treated at the Neurology Clinic of the University Clinical Center of Serbia in Belgrade, from February 2018 to December 2023, who had atherosclerotic CSVD confirmed by neuroimaging and underwent extracranial color duplex sonography. Data on patients' gender, age, cerebrovascular risk factors (dyslipidemia, hypertension, diabetes mellitus, smoking status), ultrasonography findings (intima-media thickness - IMT, carotid and vertebral artery stenosis, and hemodynamics), and CSVD imaging markers were collected, and the CSVD MRI burden score was calculated. Results Age correlated with LS and WMH (p < 0.05 for both). Hypertension correlated with WMH (p = 0.016), and smoking with LS (p = 0.043). Brain atrophy was more common in women (p = 0.016). The majority of patients had low-grade (<50 %) carotid stenosis. There was a strong correlation between all morphological parameters of internal carotid artery stenosis and the CSVD burden score (p < 0.05 for all). The hemodynamic parameters of internal carotid artery stenosis and morphological and hemodynamic parameters of vertebral artery stenosis didn't correlate with the CSVD burden score. Conclusions This study shows a strong correlation between cerebral large and small vessel pathology. We recommend the use of extracranial color duplex sonography in the evaluation of patients with CSVD as a supplementary method for follow-up, as this would allow the identification of patients whose condition might progress.
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Affiliation(s)
| | - Mirjana Zdraljevic
- Neurology Clinic, University Clinical Center of Serbia, 11000, Belgrade, Serbia
| | - Aleksandra Radojicic
- Faculty of Medicine University of Belgrade, 11000, Belgrade, Serbia
- Neurology Clinic, University Clinical Center of Serbia, 11000, Belgrade, Serbia
| | - Aleksandra Pavlovic
- Faculty of Special Education and Rehabilitation, University of Belgrade, 11000, Belgrade, Serbia
| | - Milija Mijajlovic
- Faculty of Medicine University of Belgrade, 11000, Belgrade, Serbia
- Neurology Clinic, University Clinical Center of Serbia, 11000, Belgrade, Serbia
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12
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Warszawer Y, Gurevich M, Kerpel A, Dreyer Alster S, Nissan Y, Shirbint E, Hoffmann C, Achiron A. Mapping brain volume change across time in primary-progressive multiple sclerosis. Neuroradiology 2024; 66:1189-1197. [PMID: 38609687 DOI: 10.1007/s00234-024-03354-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 04/05/2024] [Indexed: 04/14/2024]
Abstract
PURPOSE Detection and prediction of the rate of brain volume loss with age is a significant unmet need in patients with primary progressive multiple sclerosis (PPMS). In this study we construct detailed brain volume maps for PPMS patients. These maps compare age-related changes in both cortical and sub-cortical regions with those in healthy individuals. METHODS We conducted retrospective analyses of brain volume using T1-weighted Magnetic Resonance Imaging (MRI) scans of a large cohort of PPMS patients and healthy subjects. The volume of brain parenchyma (BP), cortex, white matter (WM), deep gray matter, thalamus, and cerebellum were measured using the robust SynthSeg segmentation tool. Age- and gender-related regression curves were constructed based on data from healthy subjects, with the 95% prediction interval adopted as the normality threshold for each brain region. RESULTS We analyzed 495 MRI scans from 169 PPMS patients, aged 20-79 years, alongside 563 exams from healthy subjects aged 20-86. Compared to healthy subjects, a higher proportion of PPMS patients showed lower than expected brain volumes in all regions except the cerebellum. The most affected areas were BP, WM, and thalamus. Lower brain volumes correlated with longer disease duration for BP and WM, and higher disability for BP, WM, cortex, and thalamus. CONCLUSIONS Constructing age- and gender-related brain volume maps enabled identifying PPMS patients at a higher risk of brain volume loss. Monitoring these high-risk patients may lead to better treatment decisions and improve patient outcomes.
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Affiliation(s)
- Yehuda Warszawer
- Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel.
- Arrow Program for Medical Research Education, Sheba Medical Center, Ramat-Gan, Israel.
- Adelson School of Medicine, Ariel University, Ariel, Israel.
| | - Michael Gurevich
- Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Ariel Kerpel
- Department of Radiology, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Yael Nissan
- Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel
| | - Emanuel Shirbint
- Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel
| | - Chen Hoffmann
- Department of Radiology, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Anat Achiron
- Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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13
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Shao X, Shou Q, Felix K, Ojogho B, Jiang X, Gold BT, Herting MM, Goldwaser EL, Kochunov P, Hong LE, Pappas I, Braskie M, Kim H, Cen S, Jann K, Wang DJJ. Age-Related Decline in Blood-Brain Barrier Function is More Pronounced in Males than Females in Parietal and Temporal Regions. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.12.575463. [PMID: 38293052 PMCID: PMC10827081 DOI: 10.1101/2024.01.12.575463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.
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Affiliation(s)
- Xingfeng Shao
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Qinyang Shou
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Kimberly Felix
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California
| | - Brandon Ojogho
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Xuejuan Jiang
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California
- Department of Ophthalmology, Keck School of Medicine, University of Southern California
| | - Brian T. Gold
- Department of Neuroscience, College of Medicine, University of Kentucky
| | - Megan M Herting
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California
| | - Eric L Goldwaser
- Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine
- Interventional Psychiatry Program, Department of Psychiatry, Weill Cornell Medicine
| | - Peter Kochunov
- Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston
| | - L. Elliot Hong
- Louis A. Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston
| | - Ioannis Pappas
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Meredith Braskie
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Hosung Kim
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Steven Cen
- Department of Radiology and Neurology, Keck School of Medicine, University of Southern California
| | - Kay Jann
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
| | - Danny JJ Wang
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
- Department of Radiology and Neurology, Keck School of Medicine, University of Southern California
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Chien A, Wu T, Lau CY, Pandya D, Wiebold A, Agan B, Snow J, Smith B, Nath A, Nair G. White and Gray Matter Changes are Associated With Neurocognitive Decline in HIV Infection. Ann Neurol 2024; 95:941-950. [PMID: 38362961 PMCID: PMC11060903 DOI: 10.1002/ana.26896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 01/09/2024] [Accepted: 01/30/2024] [Indexed: 02/17/2024]
Abstract
OBJECTIVE To investigate the relationship between neurocognitive deficits and structural changes on brain magnetic resonance imaging in people living with HIV (PLWH) with good virological control on combination antiretroviral therapy, compared with socioeconomically matched control participants recruited from the same communities. METHODS Brain magnetic resonance imaging scans, and clinical and neuropsychological data were obtained from virologically controlled PLWH (viral load of <50 c/mL and at least 1 year of combination antiretroviral therapy) and socioeconomically matched control participants. Magnetic resonance imaging was carried out on 3 T scanner with 8-channel head coils and segmented using Classification using Derivative-based Features. Multiple regression analysis was performed to examine the association between brain volume and various clinical and neuropsychiatric parameters adjusting for age, race, and sex. To evaluate longitudinal changes in brain volumes, a random coefficient model was used to evaluate the changes over time (age) adjusting for sex and race. RESULTS The cross-sectional study included 164 PLWH and 51 controls, and the longitudinal study included 68 PLWH and 20 controls with 2 or more visits (mean 2.2 years, range 0.8-5.1 years). Gray matter (GM) atrophy rate was significantly higher in PLWH compared with control participants, and importantly, the GM and global atrophy was associated with the various neuropsychological domain scores. Higher volume of white matter hyperintensities were associated with increased atherosclerotic cardiovascular disease risk score, and decreased executive functioning and memory domain scores in PLWH. INTERPRETATION These findings suggest ongoing neurological damage even in virologically controlled participants, with significant implications for clinical management of PLWH. ANN NEUROL 2024;95:941-950.
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Affiliation(s)
- Alice Chien
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Tianxia Wu
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Chuen-Yen Lau
- National Institute of Allergy and Infectious Diseases, MD, USA
| | - Darshan Pandya
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Amanda Wiebold
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Brian Agan
- Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Joseph Snow
- National Institute of Mental Health, MD, USA
| | - Bryan Smith
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Avindra Nath
- National Institute of Neurological Disorders and Stroke, MD, USA
| | - Govind Nair
- National Institute of Neurological Disorders and Stroke, MD, USA
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15
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Mai Y, Cao Z, Zhao L, Yu Q, Xu J, Liu W, Liu B, Tang J, Luo Y, Liao W, Fang W, Ruan Y, Lei M, Mok VCT, Shi L, Liu J, for the Alzheimer's Disease Neuroimaging Initiative. The role of visual rating and automated brain volumetry in early detection and differential diagnosis of Alzheimer's disease. CNS Neurosci Ther 2024; 30:e14492. [PMID: 37864441 PMCID: PMC11017425 DOI: 10.1111/cns.14492] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 09/07/2023] [Accepted: 09/26/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD. METHODS This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M-AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index. RESULTS QMTA distinguished M-AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUCNC = 0.976, AUCMCI = 0.836, AUCMCIs = 0.894, AUCMCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA. CONCLUSIONS QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk.
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Affiliation(s)
- Yingren Mai
- Department of NeurologyThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Zhiyu Cao
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Lei Zhao
- BrainNow Research InstituteShenzhenChina
| | - Qun Yu
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Jiaxin Xu
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Wenyan Liu
- BrainNow Research InstituteShenzhenChina
| | - Bowen Liu
- Department of Statistics, College of Liberal Art and SciencesUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | - Jingyi Tang
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Yishan Luo
- BrainNow Research InstituteShenzhenChina
| | - Wang Liao
- Department of NeurologyThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Wenli Fang
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Yuting Ruan
- Department of RehabilitationThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
| | - Ming Lei
- Department of Neurology, Sun Yat‐sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Vincent C. T. Mok
- BrainNow Research InstituteShenzhenChina
- Division of Neurology, Department of Medicine and Therapeutics, Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong Kong, SARChina
| | - Lin Shi
- BrainNow Research InstituteShenzhenChina
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong Kong, SARChina
| | - Jun Liu
- Department of NeurologyThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
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Looser VN, Gerber M, Ludyga S. Physical activity and verbal memory performance: Mediating effects of resting-state brain activity. PROGRESS IN BRAIN RESEARCH 2024; 286:33-66. [PMID: 38876578 DOI: 10.1016/bs.pbr.2024.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2024]
Abstract
Verbal short-term and long-term memory are crucial neuropsychological functions involved in core cognitive abilities. They constitute vital components of subjective well-being and academic achievement. To date, there is limited research on the association between regular physical activity and memory abilities during young adulthood. The Individual Alpha Peak Frequency (IAPF) contributes to various cognitive abilities and also appears to be sensitive to physical activity. Consequently, the IAPF has the potential to underlie the association between physical activity and verbal memory. We examined the direct relation of physical activity and verbal memory, and the potential indirect relation via IAPF in young adults. Regular physical activity was assessed via accelerometry on seven consecutive days in 115 participants (N=115, 48% female) aged 18-35 years (M=24.1, SD=3.8). In addition, verbal memory performance was assessed using an immediate and delayed free-recall task. Brain activity during rest was recorded with EEG, and IAPF was extracted for mediation analyses. Path analysis revealed pronounced sex differences in the association between physical activity, IAPF, and verbal memory performance. Exclusively in female participants, higher vigorous physical activity levels were associated with better recall performance. In contrast, no association of physical activity and memory was found in male participants. However, being more physically active was related to a higher IAPF exclusively in male participants. Physical activity shows differential associations between IAPF and verbal memory in male and female participants. However, the lack of a mediating role of IAPF suggests that this neurophysiological marker cannot explain these specific associations in young adults.
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Affiliation(s)
- Vera Nina Looser
- Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland.
| | - Markus Gerber
- Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Sebastian Ludyga
- Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
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Chen J, Li T, Zhao B, Chen H, Yuan C, Garden GA, Wu G, Zhu H. The interaction effects of age, APOE and common environmental risk factors on human brain structure. Cereb Cortex 2024; 34:bhad472. [PMID: 38112569 PMCID: PMC10793588 DOI: 10.1093/cercor/bhad472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 10/09/2023] [Accepted: 11/06/2023] [Indexed: 12/21/2023] Open
Abstract
Mounting evidence suggests considerable diversity in brain aging trajectories, primarily arising from the complex interplay between age, genetic, and environmental risk factors, leading to distinct patterns of micro- and macro-cerebral aging. The underlying mechanisms of such effects still remain unclear. We conducted a comprehensive association analysis between cerebral structural measures and prevalent risk factors, using data from 36,969 UK Biobank subjects aged 44-81. Participants were assessed for brain volume, white matter diffusivity, Apolipoprotein E (APOE) genotypes, polygenic risk scores, lifestyles, and socioeconomic status. We examined genetic and environmental effects and their interactions with age and sex, and identified 726 signals, with education, alcohol, and smoking affecting most brain regions. Our analysis revealed negative age-APOE-ε4 and positive age-APOE-ε2 interaction effects, respectively, especially in females on the volume of amygdala, positive age-sex-APOE-ε4 interaction on the cerebellar volume, positive age-excessive-alcohol interaction effect on the mean diffusivity of the splenium of the corpus callosum, positive age-healthy-diet interaction effect on the paracentral volume, and negative APOE-ε4-moderate-alcohol interaction effects on the axial diffusivity of the superior fronto-occipital fasciculus. These findings highlight the need of considering age, sex, genetic, and environmental joint effects in elucidating normal or abnormal brain aging.
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Affiliation(s)
- Jie Chen
- Department of Biostatistics, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill NC 27514, United States
| | - Tengfei Li
- Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, United States
- Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, 125 Mason Farm Road, Chapel Hill, NC 27599, United States
| | - Bingxin Zhao
- Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, 265 South 37th Street, 3rd & 4th Floors, Philadelphia, PA 19104-1686, United States
| | - Hui Chen
- School of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou 310058, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou 310058, China
- Department of Nutrition, Harvard T H Chan School of Public Health, 665 Huntington Avenue Boston, MA, 02115, United States
| | - Gwenn A Garden
- Department of Neurology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive Chapel Hill, NC 27599-7025, United States
| | - Guorong Wu
- Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, United States
- Departments of Statistics and Operations Research, University of North Carolina at Chapel Hill, 318 E Cameron Ave #3260, Chapel Hill, NC 27599, United States
- Departments of Computer Science, University of North Carolina at Chapel Hill, 201 South Columbia Street, Chapel Hill, NC 27599, United States
- UNC Neuroscience Center, University of North Carolina at Chapel Hill, 116 Manning Dr, Chapel Hill, NC 27599, United States
- Carolina Institute for Developmental Disabilities, 101 Renee Lynne Ct, Carrboro, NC 27510, United States
| | - Hongtu Zhu
- Department of Biostatistics, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill NC 27514, United States
- Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, 125 Mason Farm Road, Chapel Hill, NC 27599, United States
- Departments of Statistics and Operations Research, University of North Carolina at Chapel Hill, 318 E Cameron Ave #3260, Chapel Hill, NC 27599, United States
- Departments of Computer Science, University of North Carolina at Chapel Hill, 201 South Columbia Street, Chapel Hill, NC 27599, United States
- Departments of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27514, United States
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Canjels LPW, Alers RJ, van de Ven V, Hurks PPM, Gerretsen SC, Brandt Y, Kooi ME, Jansen JFA, Backes WH, Ghossein-Doha C, Spaanderman MEA. Cerebral volume is unaffected after pre-eclampsia. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2023; 62:115-121. [PMID: 36730173 DOI: 10.1002/uog.26172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 01/12/2023] [Accepted: 01/19/2023] [Indexed: 06/18/2023]
Abstract
OBJECTIVES Pre-eclampsia has been associated with cardiovascular, cerebrovascular and/or psychological complaints. Signs of altered brain morphology and more white-matter hyperintensities (WMHs) during and shortly after pre-eclampsia have been observed in some, but not all, studies. We compared volumes of cerebral structures and the number of WMHs between formerly pre-eclamptic women and those with normotensive gestational history and assessed the effect of age on brain volumes. METHODS Structural 7-Tesla magnetic resonance imaging of the brain was performed in 59 formerly pre-eclamptic women (aged 37 ± 6 years, 0.5-16 years postpartum) and 20 women with a history of normotensive pregnancy (aged 39 ± 5 years, 1-18 years postpartum). Fazekas scores were obtained to assess WMH load. Volumes of the whole brain, gray and white matter, brain lobes, and ventricular and pericortical cerebrospinal fluid (CSF) spaces were calculated after semiautomatic segmentation. Group differences were analyzed using ANCOVA and Bayes factors. Results were adjusted for age, educational attainment, presence of current hypertension and total intracranial volume. The effect of age on cerebral volumes was analyzed using linear regression analysis. RESULTS No changes in global and local brain volumes were observed between formerly pre-eclamptic and control women. Also, no difference in WMH load was observed. Independent of pre-eclamptic history, gray-matter volume significantly decreased with age, while ventricular and pericortical CSF space volumes significantly increased with age. CONCLUSIONS Volumetric changes of the cerebrum are age-related but are independent of pre-eclamptic history in the first two decades after childbirth. No evidence of greater WMH load after pre-eclampsia was found. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- L P W Canjels
- Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - R J Alers
- Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands
| | - V van de Ven
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - P P M Hurks
- Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - S C Gerretsen
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Y Brandt
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, The Netherlands
| | - M E Kooi
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, The Netherlands
| | - J F A Jansen
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - W H Backes
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, The Netherlands
- School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands
| | - C Ghossein-Doha
- School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, The Netherlands
- Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - M E A Spaanderman
- Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands
- School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
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Han G, Zhou Y, Zhang K, Jiao B, Hu J, Zhang Y, Wang Z, Lou M, Bai R. Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods. Front Aging Neurosci 2023; 15:1173221. [PMID: 37284019 PMCID: PMC10239807 DOI: 10.3389/fnagi.2023.1173221] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/04/2023] [Indexed: 06/08/2023] Open
Abstract
Advanced age, accompanied by impaired glymphatic function, is a key risk factor for many neurodegenerative diseases. To study age-related differences in the human glymphatic system, we measured the influx and efflux activities of the glymphatic system via two non-invasive diffusion magnetic resonance imaging (MRI) methods, ultra-long echo time and low-b diffusion tensor imaging (DTIlow-b) measuring the subarachnoid space (SAS) flow along the middle cerebral artery and DTI analysis along the perivascular space (DTI-ALPS) along medullary veins in 22 healthy volunteers (aged 21-75 years). We first evaluated the circadian rhythm dependence of the glymphatic activity by repeating the MRI measurements at five time points from 8:00 to 23:00 and found no time-of-day dependence in the awake state under the current sensitivity of MRI measurements. Further test-retest analysis demonstrated high repeatability of both diffusion MRI measurements, suggesting their reliability. Additionally, the influx rate of the glymphatic system was significantly higher in participants aged >45 years than in participants aged 21-38, while the efflux rate was significantly lower in those aged >45 years. The mismatched influx and efflux activities in the glymphatic system might be due to age-related changes in arterial pulsation and aquaporin-4 polarization.
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Affiliation(s)
- Guangxu Han
- Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Ying Zhou
- Department of Neurology, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Kemeng Zhang
- Department of Neurology, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Bingjie Jiao
- Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Junwen Hu
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, China
| | - Yifan Zhang
- Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Zejun Wang
- Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
| | - Min Lou
- Department of Neurology, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Ruiliang Bai
- Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
- MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China
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20
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Nicoletti A, Baschi R, Cicero CE, Iacono S, Re VL, Luca A, Schirò G, Monastero R. Sex and gender differences in Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis: a narrative review. Mech Ageing Dev 2023; 212:111821. [PMID: 37127082 DOI: 10.1016/j.mad.2023.111821] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 04/24/2023] [Accepted: 04/27/2023] [Indexed: 05/03/2023]
Abstract
Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), exhibit high phenotypic variability and they are very common in the general population. These diseases are associated with poor prognosis and a significant burden on patients and their caregivers. Although increasing evidence suggests that biological sex is an important factor for the development and phenotypical expression of some NDs, the role of sex and gender in the diagnosis and prognosis of NDs has been poorly explored. Current knowledge relating to sex- and gender-related differences in the epidemiology, clinical features, biomarkers, and treatment of AD, PD, and ALS will be summarized in this narrative review. The cumulative evidence hitherto collected suggests that sex and gender are factors to be considered in explaining the heterogeneity of these NDs. Clarifying the role of sex and gender in AD, PD, and ALS is a key topic in precision medicine, which will facilitate sex-specific prevention and treatment strategies to be implemented in the near future.
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Affiliation(s)
- Alessandra Nicoletti
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
| | - Roberta Baschi
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy
| | - Calogero Edoardo Cicero
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Salvatore Iacono
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy
| | - Vincenzina Lo Re
- Neurology Service, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Via Ernesto Tricomi 5, 90127 Palermo, Italy; Women's Brain Project, Guntershausen, Switzerland
| | - Antonina Luca
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Giuseppe Schirò
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy
| | - Roberto Monastero
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy.
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21
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Arinze JT, Vinke EJ, Verhamme KMC, de Ridder MAJ, Stricker B, Ikram MK, Brusselle G, Vernooij MW. Chronic Cough-Related Differences in Brain Morphometry in Adults: A Population-Based Study. Chest 2023:S0012-3692(23)00187-3. [PMID: 36781103 DOI: 10.1016/j.chest.2023.02.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 02/02/2023] [Accepted: 02/06/2023] [Indexed: 02/13/2023] Open
Abstract
BACKGROUND Individuals with cough hypersensitivity have increased central neural responses to tussive stimuli, which may result in maladaptive morphometric changes in the central cough processing systems. RESEARCH QUESTION Are the volumes of the brain regions implicated in cough hypersensitivity different in adults with chronic cough compared with adults without chronic cough? STUDY DESIGN AND METHODS Between 2009 and 2014, participants in the Rotterdam Study, a population-based cohort, underwent brain MRI and were interviewed for chronic cough, which was defined as daily coughing for at least 3 months. Regional brain volumes were quantified with the use of parcellation software. Based on literature review, we identified and studied seven brain regions that previously had been associated with altered functional brain activity in chronic cough. The relationship between chronic cough and regional brain volumes was investigated with the use of multivariable regression models. RESULTS Chronic cough was prevalent in 9.6% (No. = 349) of the 3,620 study participants (mean age, 68.5 ± 9.0 years; 54.6% women). Participants with chronic cough had significantly smaller anterior cingulate cortex volume than participants without chronic cough (mean difference, -126.16 mm3; 95% CI, -245.67 to -6.66; P = .039). Except for anterior cingulate cortex, there were no significant difference in the volume of other brain regions based on chronic cough status. The volume difference in the anterior cingulate cortex was more pronounced in the left hemisphere (mean difference, -88.11 mm3; 95% CI, -165.16 to -11.06; P = .025) and in men (mean difference, -242.58 mm3; 95% CI, -428.60 to -56.55; P = .011). INTERPRETATION Individuals with chronic cough have a smaller volume of the anterior cingulate cortex, which is a brain region involved in cough suppression. CLINICAL TRIAL REGISTRATION The Netherlands National Trial Registry (NTR; www.trialregister.nl) and the World Health Organization's International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under the joint catalogue number NTR6831.
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Affiliation(s)
- Johnmary T Arinze
- Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Elisabeth J Vinke
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Katia M C Verhamme
- Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Maria A J de Ridder
- Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Bruno Stricker
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - M K Ikram
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Guy Brusselle
- Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Meike W Vernooij
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
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22
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Kashyap R, Bhattacharjee S, Bharath RD, Venkatasubramanian G, Udupa K, Bashir S, Oishi K, Desmond JE, Chen SHA, Guan C. Variation of cerebrospinal fluid in specific regions regulates focality in transcranial direct current stimulation. Front Hum Neurosci 2022; 16:952602. [PMID: 36118967 PMCID: PMC9479459 DOI: 10.3389/fnhum.2022.952602] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background Conventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality ("non-focal"). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality. Aim To determine the regional volume parameters that differentiate the focal and non-focal groups. Methods T1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV's showed a significant main effect or interaction involving the focality group, then that ROI was classified as a "focal ROI." Results Regional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ -0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses. Conclusion The CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL).
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Affiliation(s)
- Rajan Kashyap
- Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
- School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore
| | - Sagarika Bhattacharjee
- Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India
- Psychology, School of Social Sciences (SSS), Nanyang Technological University, Singapore, Singapore
| | - Rose Dawn Bharath
- Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
| | - Ganesan Venkatasubramanian
- InSTAR Program, Schizophrenia Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
| | - Kaviraja Udupa
- Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Shahid Bashir
- Neuroscience Center, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Kenichi Oishi
- The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - John E. Desmond
- The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - S. H. Annabel Chen
- Psychology, School of Social Sciences (SSS), Nanyang Technological University, Singapore, Singapore
- Centre for Research and Development in Learning (CRADLE), Nanyang Technological University, Singapore, Singapore
- Lee Kong Chian School of Medicine (LKC Medicine), Nanyang Technological University, Singapore, Singapore
- National Institute of Education, Nanyang Technological University, Singapore, Singapore
| | - Cuntai Guan
- School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore
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23
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Influence of current physical exercise on the relationship between aging and episodic memory and fluid intelligence. Acta Psychol (Amst) 2022; 227:103609. [PMID: 35569203 DOI: 10.1016/j.actpsy.2022.103609] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 04/09/2022] [Accepted: 05/04/2022] [Indexed: 11/24/2022] Open
Abstract
The present study examined the effects of current physical exercise and age on episodic memory and fluid intelligence, assessed with a free-recall task and the Culture Fair Intelligence Test (Cattell, 1963) respectively, while statistically controlling for other cognitive reserve factors (educational level, leisure activities, and vocabulary level). Two hundred and eight participants aged 20 to 85 participated in the study. Physical exercise level was indexed by weekly frequency over the last 12 months using self-reported measurement (from none to 4 times a week). Overall, results show a beneficial effect of physical exercise especially from a weekly practice of 2 times, and significant interaction between physical exercise and age on episodic memory and fluid intelligence capacities indicating a reduced effect of age in more physically active participants. These results reinforce the view that physical exercise is a strong and specific reserve factor that reduces decline in some cognitive functions during aging.
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Wang H, Burles F, Subramaniapillai S, Pasvanis S, Rajah MN, Protzner AB. Sex differences in the relationship between age, performance, and BOLD signal variability during spatial context memory processing. Neurobiol Aging 2022; 118:77-87. [DOI: 10.1016/j.neurobiolaging.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 10/17/2022]
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Yang Z, Caldwell JZK, Cummings JL, Ritter A, Kinney JW, Cordes D. Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment. Front Psychiatry 2022; 13:804168. [PMID: 35479489 PMCID: PMC9037326 DOI: 10.3389/fpsyt.2022.804168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/14/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose To assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process. Materials and Methods Two hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI. Results The MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10-7, right: P = 3.37 × 10-8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI. Conclusion Sex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.
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Affiliation(s)
- Zhengshi Yang
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
- Department of Brain Health, University of Nevada Las Vegas, Las Vegas, NV, United States
| | | | - Jeffrey L. Cummings
- Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States
| | - Aaron Ritter
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
| | - Jefferson W. Kinney
- Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States
| | - Dietmar Cordes
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
- Department of Brain Health, University of Nevada Las Vegas, Las Vegas, NV, United States
- Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, United States
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26
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Austin TR, Nasrallah IM, Erus G, Desiderio LM, Chen LY, Greenland P, Harding BN, Hughes TM, Jensen PN, Longstreth WT, Post WS, Shea SJ, Sitlani CM, Davatzikos C, Habes M, Nick Bryan R, Heckbert SR. Association of Brain Volumes and White Matter Injury With Race, Ethnicity, and Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2022; 11:e023159. [PMID: 35352569 PMCID: PMC9075451 DOI: 10.1161/jaha.121.023159] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 02/22/2022] [Indexed: 11/16/2022]
Abstract
Background Cardiovascular risk factors are associated with cognitive decline and dementia. Magnetic resonance imaging provides sensitive measurement of brain morphology and vascular brain injury. However, associations of risk factors with brain magnetic resonance imaging findings have largely been studied in White participants. We investigated associations of race, ethnicity, and cardiovascular risk factors with brain morphology and white matter (WM) injury in a diverse population. Methods and Results In the Multi-Ethnic Study of Atherosclerosis, measures were made in 2018 to 2019 of total brain volume, gray matter and WM volume, and WM injury, including WM hyperintensity volume and WM fractional anisotropy. We assessed cross-sectional associations of race and ethnicity and of cardiovascular risk factors with magnetic resonance imaging measures. Magnetic resonance imaging data were complete in 1036 participants; 25% Black, 15% Chinese-American, 19% Hispanic, and 41% White. Mean (SD) age was 72 (8) years and 53% were women. Although WM injury was greater in Black than in White participants in a minimally adjusted model, additional adjustment for cardiovascular risk factors and socioeconomic status each attenuated this association, rendering it nonsignificant. Overall, greater average WM hyperintensity volume was associated with older age and current smoking (69% greater vs never smoking); lower fractional anisotropy was additionally associated with higher diastolic blood pressure, use of antihypertensive medication, and diabetes. Conclusions We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. In all racial and ethnic groups, older age, current smoking, hypertension, and diabetes were strongly associated with WM injury.
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Affiliation(s)
| | | | - Guray Erus
- Department of RadiologyUniversity of PennsylvaniaPhiladelphiaPA
| | | | - Lin Y. Chen
- Cardiovascular DivisionUniversity of MinnesotaMinneapolisMN
| | - Philip Greenland
- Department of Preventative Medicine and Department of MedicineFeinberg School of MedicineChicagoIL
| | | | - Timothy M. Hughes
- Department of Internal MedicineWake Forest School of MedicineWinston‐SalemNC
| | | | - WT Longstreth
- Department of EpidemiologyUniversity of WashingtonSeattleWA
- Department of NeurologyUniversity of WashingtonSeattleWA
| | - Wendy S. Post
- Division of CardiologyDepartment of MedicineJohns Hopkins UniversityBaltimoreMaryland
| | - Steven J. Shea
- Departments of Medicine and EpidemiologyColumbia UniversityNew YorkNY
| | | | | | - Mohamad Habes
- Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging CoreGlenn Biggs Institute for Alzheimer’s & Neurodegenerative DiseasesUniversity of Texas Health Science Center San AntonioTX
| | - R. Nick Bryan
- Department of Diagnostic MedicineUniversity of Texas at AustinAustinTX
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27
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Zhong XZ, Chen JJ. Resting-state functional magnetic resonance imaging signal variations in aging: The role of neural activity. Hum Brain Mapp 2022; 43:2880-2897. [PMID: 35293656 PMCID: PMC9120570 DOI: 10.1002/hbm.25823] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 01/20/2022] [Accepted: 02/23/2022] [Indexed: 11/23/2022] Open
Abstract
Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been extensively used to study brain aging, but the age effect on the frequency content of the rs‐fMRI signal has scarcely been examined. Moreover, the neuronal implications of such age effects and age–sex interaction remain unclear. In this study, we examined the effects of age and sex on the rs‐fMRI signal frequency using the Leipzig mind–brain–body data set. Over a frequency band of up to 0.3 Hz, we found that the rs‐fMRI fluctuation frequency is higher in the older adults, although the fluctuation amplitude is lower. The rs‐fMRI signal frequency is also higher in men than in women. Both age and sex effects on fMRI frequency vary with the frequency band examined but are not found in the frequency of physiological‐noise components. This higher rs‐fMRI frequency in older adults is not mediated by the electroencephalograph (EEG)‐frequency increase but a likely link between fMRI signal frequency and EEG entropy, which vary with age and sex. Additionally, in different rs‐fMRI frequency bands, the fMRI‐EEG amplitude ratio is higher in young adults. This is the first study to investigate the neuronal contribution to age and sex effects in the frequency dimension of the rs‐fMRI signal and may lead to the development of new, frequency‐based rs‐fMRI metrics. Our study demonstrates that Fourier analysis of the fMRI signal can reveal novel information about aging. Furthermore, fMRI and EEG signals reflect different aspects of age‐ and sex‐related brain differences, but the signal frequency and complexity, instead of amplitude, may hold their link.
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Affiliation(s)
- Xiaole Z Zhong
- Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - J Jean Chen
- Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.,Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
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28
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Larnyo E, Dai B, Nutakor JA, Ampon-Wireko S, Larnyo A, Appiah R. Examining the impact of socioeconomic status, demographic characteristics, lifestyle and other risk factors on adults' cognitive functioning in developing countries: an analysis of five selected WHO SAGE Wave 1 Countries. Int J Equity Health 2022; 21:31. [PMID: 35216605 PMCID: PMC8876754 DOI: 10.1186/s12939-022-01622-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 01/24/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Though extensive studies have been conducted on assessing the predictors of cognitive functioning among older adults in small community-based samples, very few studies have focused on understanding the impact of socioeconomic status (SES), demographic characteristics and other risk factors such as lifestyle and chronic diseases on the cognitive functioning among adults of all ages in a nationally representative population-based sample across low- and middle-income countries. This study, therefore, seeks to evaluate the impact of SES, demographic characteristics and risk factors on the cognitive functioning of adults across all ages in five selected developing countries. METHODS Data from 12,430 observations obtained from the WHO Study on Global AGEing and Adult Health (SAGE) Wave 1; consisting of 2,486 observations each for China, Ghana, India, the Russian Federation, and South Africa, were used for the study. A meta-regression and a five-step hierarchical linear regression were used to analyze the data, with cognitive functioning as the dependent variable. Independent variables used in this study include SES; assessed by household income and education, demographic characteristics, other risk factors such as lifestyle, self-reported memory difficulty and chronic diseases. RESULTS This study found that SES and lifestyle significantly predicted cognitive functioning in all the five selected countries as obtained by the pooled results of the meta-regression analysis. The hierarchical linear regression results also revealed that demographic characteristics such as age, type of residency, and self-reported memory difficulty significantly impact cognitive functioning in China, Ghana, Russia, and South Africa. CONCLUSION The findings in this study provide new insights for policymakers, caregivers, parents, and individuals, especially those in developing countries, to implement policies and actions targeted at improving SES and eliminating risk factors associated with cognitive decline, as these measures could help improve the cognitive functioning among their populations.
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Affiliation(s)
- Ebenezer Larnyo
- Department of Health Policy and Management, School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China
| | - Baozhen Dai
- Department of Health Policy and Management, School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China.
- Department of Labor and Social Security, School of Public Health, Southeast University, 87# Dingjiaqiao, Nanjing, 210009, Jiangsu province, China.
| | - Jonathan Aseye Nutakor
- Department of Health Policy and Management, School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China
| | - Sabina Ampon-Wireko
- Department of Health Policy and Management, School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China
| | - Abigail Larnyo
- School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China
| | - Ruth Appiah
- Department of Health Policy and Management, School of Management, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China
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29
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Gardeniers MKM, van Groenou MIB, Meijboom EJ, Huisman M. Three-year trajectories in functional limitations and cognitive decline among Dutch 75+ year olds, using nine-month intervals. BMC Geriatr 2022; 22:89. [PMID: 35105338 PMCID: PMC8805337 DOI: 10.1186/s12877-021-02720-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 12/03/2021] [Indexed: 11/29/2022] Open
Abstract
Background Using longitudinal panel data, we aimed to identify three-year trajectories in cognitive and physical functioning among Dutch older adults, and the characteristics associated with these trajectories. Methods We used Group-based Trajectory Modelling with mortality jointly estimated to identify trajectories, using a scale composed of 6 Activities of Daily Living (ADL) as a measure of physical functioning, and the short mini mental status examination (sMMSE) or the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a measure of cognitive functioning. Data came from 574 Dutch adults aged 75+, collected in five nine-month measurement waves (2015–2018) for the Longitudinal Aging Study Amsterdam. Results For physical functioning five trajectories were identified: ‘high’, ‘moderate’, ‘steeply declining’, ‘gradually declining’, and ‘continuously low’; and for cognitive functioning: ‘high’, ‘moderate’, ‘declining’, and ‘low’. Living in an institution, and being lower educated increased the probability of the two continuously low functioning trajectories, whereas old age and multimorbidity increased the probability of low physical functioning, but multimorbidity decreased the probability of low cognitive functioning. Associations for steeply declining physical functioning were absent. Being older and having multimorbidity increased the probability of gradually declining physical functioning and declining cognitive functioning. A higher prevalence of lung- and heart disease, cancer, and rheumatic disease was found in the gradually declining physical functioning group; and a higher prevalence of diabetes, cerebrovascular accidents, and cancer was found in the declining cognitive functioning group. High and moderate physical functioning and high cognitive functioning were characterized by being younger, community-dwelling, and higher educated. Having multimorbidity negatively predicted high and moderate physical functioning, but was not associated with high and moderate cognitive functioning. Conclusions This study identified trajectories comparable to studies that used longer time intervals, showing the consistent presence of heterogeneity in both physical and cognitive trajectories. Co-modelling mortality resulted in bigger group sizes for the more adverse trajectories. The favourable trajectories, containing most of the participants, were mostly characterized by absence of disease. The prevalence of chronic diseases differed between the declining trajectories, suggesting that certain diseases tend to induce cognitive decline rather than physical decline, and vice versa. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-021-02720-x.
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Affiliation(s)
| | | | - Erik Jan Meijboom
- Department of Sociology, Vrije Universiteit Amsterdam, De Boelelaan, 1081, Amsterdam, The Netherlands
| | - Martijn Huisman
- Department of Epidemiology & Biostatistics, Amsterdam Public Health research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, Netherlands
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30
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Statsenko Y, Habuza T, Smetanina D, Simiyu GL, Uzianbaeva L, Neidl-Van Gorkom K, Zaki N, Charykova I, Al Koteesh J, Almansoori TM, Belghali M, Ljubisavljevic M. Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes. Front Aging Neurosci 2022; 13:713680. [PMID: 35153713 PMCID: PMC8826453 DOI: 10.3389/fnagi.2021.713680] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 09/27/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one. OBJECTIVE To work out a descriptive model of brain structural and functional changes in normal aging. MATERIALS AND METHODS By using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U-test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T-test. RESULTS White matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age. CONCLUSION The article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results.
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Affiliation(s)
- Yauhen Statsenko
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Tetiana Habuza
- Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates
- College of Information Technology, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Darya Smetanina
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Gillian Lylian Simiyu
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Liaisan Uzianbaeva
- Department of Biomedical Engineering, Wayne State University, Detroit, MI, United States
- Department of Obstetrics and Gynecology, Bronxcare Hospital System, Bronx, NY, United States
| | - Klaus Neidl-Van Gorkom
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Nazar Zaki
- Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates
- College of Information Technology, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Inna Charykova
- Laboratory of Psychology, Republican Scientific-Practical Center of Sports, Minsk, Belarus
| | - Jamal Al Koteesh
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- Department of Radiology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Taleb M. Almansoori
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Maroua Belghali
- Department of Health and Physical Education, College of Education, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Milos Ljubisavljevic
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
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31
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Statsenko Y, Habuza T, Gorkom KNV, Zaki N, Almansoori TM, Al Zahmi F, Ljubisavljevic MR, Belghali M. Proportional Changes in Cognitive Subdomains During Normal Brain Aging. Front Aging Neurosci 2021; 13:673469. [PMID: 34867263 PMCID: PMC8634589 DOI: 10.3389/fnagi.2021.673469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 09/20/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Neuroscience lacks a reliable method of screening the early stages of dementia. Objective: To improve the diagnostics of age-related cognitive functions by developing insight into the proportionality of age-related changes in cognitive subdomains. Materials and Methods: We composed a battery of psychophysiological tests and collected an open-access psychophysiological outcomes of brain atrophy (POBA) dataset by testing individuals without dementia. To extend the utility of machine learning (ML) classification in cognitive studies, we proposed estimates of the disproportional changes in cognitive functions: an index of simple reaction time to decision-making time (ISD), ISD with the accuracy performance (ISDA), and an index of performance in simple and complex visual-motor reaction with account for accuracy (ISCA). Studying the distribution of the values of the indices over age allowed us to verify whether diverse cognitive functions decline equally throughout life or there is a divergence in age-related cognitive changes. Results: Unsupervised ML clustering shows that the optimal number of homogeneous age groups is four. The sample is segregated into the following age-groups: Adolescents ∈ [0, 20), Young adults ∈ [20, 40), Midlife adults ∈ [40, 60) and Older adults ≥60 year of age. For ISD, ISDA, and ISCA values, only the median of the Adolescents group is different from that of the other three age-groups sharing a similar distribution pattern (p > 0.01). After neurodevelopment and maturation, the indices preserve almost constant values with a slight trend toward functional decline. The reaction to a moving object (RMO) test results (RMO_mean) follow another tendency. The Midlife adults group's median significantly differs from the remaining three age subsamples (p < 0.01). No general trend in age-related changes of this dependent variable is observed. For all the data (ISD, ISDA, ISCA, and RMO_mean), Levene's test reveals no significant changes of the variances in age-groups (p > 0.05). Homoscedasticity also supports our assumption about a linear dependency between the observed features and age. Conclusion: In healthy brain aging, there are proportional age-related changes in the time estimates of information processing speed and inhibitory control in task switching. Future studies should test patients with dementia to determine whether the changes of the aforementioned indicators follow different patterns.
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Affiliation(s)
- Yauhen Statsenko
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.,Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Tetiana Habuza
- Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates.,Department of Computer Science and Software Engineering, College of Information Technology, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Klaus Neidl-Van Gorkom
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Nazar Zaki
- Big Data Analytics Center, United Arab Emirates University, Al Ain, United Arab Emirates.,Department of Computer Science and Software Engineering, College of Information Technology, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Taleb M Almansoori
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Fatmah Al Zahmi
- Department of Neurology, Mediclinic Middle East Parkview Hospital, Dubai, United Arab Emirates.,Department of Clinical Science, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Milos R Ljubisavljevic
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Maroua Belghali
- College of Education, United Arab Emirates University, Al Ain, United Arab Emirates
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Yee E, Ma D, Popuri K, Chen S, Lee H, Chow V, Ma C, Wang L, Beg MF. 3D hemisphere-based convolutional neural network for whole-brain MRI segmentation. Comput Med Imaging Graph 2021; 95:102000. [PMID: 34839147 PMCID: PMC10116838 DOI: 10.1016/j.compmedimag.2021.102000] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/30/2021] [Accepted: 10/04/2021] [Indexed: 10/19/2022]
Abstract
Whole-brain segmentation is a crucial pre-processing step for many neuroimaging analyses pipelines. Accurate and efficient whole-brain segmentations are important for many neuroimage analysis tasks to provide clinically relevant information. Several recently proposed convolutional neural networks (CNN) perform whole brain segmentation using individual 2D slices or 3D patches as inputs due to graphical processing unit (GPU) memory limitations, and use sliding windows to perform whole brain segmentation during inference. However, these approaches lack global and spatial information about the entire brain and lead to compromised efficiency during both training and testing. We introduce a 3D hemisphere-based CNN for automatic whole-brain segmentation of T1-weighted magnetic resonance images of adult brains. First, we trained a localization network to predict bounding boxes for both hemispheres. Then, we trained a segmentation network to segment one hemisphere, and segment the opposing hemisphere by reflecting it across the mid-sagittal plane. Our network shows high performance both in terms of segmentation efficiency and accuracy (0.84 overall Dice similarity and 6.1 mm overall Hausdorff distance) in segmenting 102 brain structures. On multiple independent test datasets, our method demonstrated a competitive performance in the subcortical segmentation task and a high consistency in volumetric measurements of intra-session scans.
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Affiliation(s)
- Evangeline Yee
- School of Engineering Science, Simon Fraser University, Canada
| | - Da Ma
- School of Engineering Science, Simon Fraser University, Canada
| | - Karteek Popuri
- School of Engineering Science, Simon Fraser University, Canada
| | - Shuo Chen
- School of Engineering Science, Simon Fraser University, Canada
| | - Hyunwoo Lee
- School of Engineering Science, Simon Fraser University, Canada; Division of Neurology, Department of Medicine, University of British Columbia, Canada
| | - Vincent Chow
- School of Engineering Science, Simon Fraser University, Canada
| | - Cydney Ma
- School of Engineering Science, Simon Fraser University, Canada
| | - Lei Wang
- Department of Psychiatry and Behavioral Health, College of Medicine, The Ohio State University, Canada; Feinberg School of Medicine, Northwest University, Canada
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Caulfield KA, Li X, George MS. A reexamination of motor and prefrontal TMS in tobacco use disorder: Time for personalized dosing based on electric field modeling? Clin Neurophysiol 2021; 132:2199-2207. [PMID: 34298414 PMCID: PMC8384673 DOI: 10.1016/j.clinph.2021.06.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 06/05/2021] [Accepted: 06/09/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVE In this study, we reexamined the use of 120% resting motor threshold (rMT) dosing for transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) using electric field modeling. METHODS We computed electric field models in 38 tobacco use disorder (TUD) participants to compare figure-8 coil induced electric fields at 100% rMT over the primary motor cortex (M1), and 100% and 120% rMT over the DLPFC. We then calculated the percentage of rMT needed for motor-equivalent induced electric fields at the DLPFC and modeled this intensity for each person. RESULTS Electric fields from 100% rMT stimulation over M1 were significantly larger than what was modeled in the DLPFC using 100% rMT (p < 0.001) and 120% rMT stimulation (p = 0.013). On average, TMS would need to be delivered at 133.5% rMT (range = 79.9 to 247.5%) to produce motor-equivalent induced electric fields at the DLPFC of 158.2 V/m. CONCLUSIONS TMS would have to be applied at an average of 133.5% rMT over the left DLPFC to produce equivalent electric fields to 100% rMT stimulation over M1 in these 38 TUD patients. The high interindividual variability between motor and prefrontal electric fields for each participant supports using personalized electric field modeling for TMS dosing to ensure that each participant is not under- or over-stimulated. SIGNIFICANCE These electric field modeling in TUD data suggest that 120% rMT stimulation over the DLPFC delivers sub-motor equivalent electric fields in many individuals (73.7%). With further validation, electric field modeling may be an impactful method of individually dosing TMS.
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Affiliation(s)
- Kevin A Caulfield
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA.
| | - Xingbao Li
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
| | - Mark S George
- Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA
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Age- and gender-related differences in brain tissue microstructure revealed by multi-component T 2 relaxometry. Neurobiol Aging 2021; 106:68-79. [PMID: 34252873 DOI: 10.1016/j.neurobiolaging.2021.06.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 05/30/2021] [Accepted: 06/01/2021] [Indexed: 12/19/2022]
Abstract
In spite of extensive work, inconsistent findings and lack of specificity in most neuroimaging techniques used to examine age- and gender-related patterns in brain tissue microstructure indicate the need for additional research. Here, we performed the largest Multi-component T2 relaxometry cross-sectional study to date in healthy adults (N = 145, 18-60 years). Five quantitative microstructure parameters derived from various segments of the estimated T2 spectra were evaluated, allowing a more specific interpretation of results in terms of tissue microstructure. We found similar age-related myelin water fraction (MWF) patterns in men and women but we also observed differential male related results including increased MWF content in a few white matter tracts, a faster decline with age of the intra- and extra-cellular water fraction and its T2 relaxation time (i.e. steeper age related negative slopes) and a faster increase in the free and quasi-free water fraction, spanning the whole grey matter. Such results point to a sexual dimorphism in brain tissue microstructure and suggest a lesser vulnerability to age-related changes in women.
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Irimia A. Cross-Sectional Volumes and Trajectories of the Human Brain, Gray Matter, White Matter and Cerebrospinal Fluid in 9473 Typically Aging Adults. Neuroinformatics 2021; 19:347-366. [PMID: 32856237 DOI: 10.1007/s12021-020-09480-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Accurate knowledge of adult human brain volume (BV) is critical for studies of aging- and disease-related brain alterations, and for monitoring the trajectories of neural and cognitive functions in conditions like Alzheimer's disease and traumatic brain injury. This scoping meta-analysis aggregates normative reference values for BV and three related volumetrics-gray matter volume (GMV), white matter volume (WMV) and cerebrospinal fluid volume (CSFV)-from typically-aging adults studied cross-sectionally using magnetic resonance imaging (MRI). Drawing from an aggregate sample of 9473 adults, this study provides (A) regression coefficients β describing the age-dependent trajectories of volumetric measures by sex within the range from 20 to 70 years based on both linear and quadratic models, and (B) average values for BV, GMV, WMV and CSFV at the representative ages of 20 (young age), 45 (middle age) and 70 (old age). The results provided synthesize ~20 years of brain volumetrics research and allow one to estimate BV at any age between 20 and 70. Importantly, however, such estimates should be used and interpreted with caution because they depend on MRI hardware specifications (e.g. scanner manufacturer, magnetic field strength), data acquisition parameters (e.g. spatial resolution, weighting), and brain segmentation algorithms. Guidelines are proposed to facilitate future meta- and mega-analyses of brain volumetrics.
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Affiliation(s)
- Andrei Irimia
- Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA, 90089, USA.
- Denney Research Center, Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, Los Angeles, CA, 90089, USA.
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Structural volume and cortical thickness differences between males and females in cognitively normal, cognitively impaired and Alzheimer's dementia population. Neurobiol Aging 2021; 106:1-11. [PMID: 34216846 DOI: 10.1016/j.neurobiolaging.2021.05.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 05/24/2021] [Accepted: 05/25/2021] [Indexed: 11/23/2022]
Abstract
We investigated differences due to sex in brain structural volume and cortical thickness in older cognitively normal (N=742), cognitively impaired (MCI; N=540) and Alzheimer's Dementia (AD; N=402) individuals from the ADNI and AIBL datasets (861 Males and 823 Females). General linear models were used to control the effect of relevant covariates including age, intracranial volume, magnetic resonance imaging (MRI) scanner field strength and scanner types. Significant volumetric differences due to sex were observed within different cortical and subcortical regions of the cognitively normal group. The number of significantly different regions was reduced in the MCI group, and no region remained different in the AD group. Cortical thickness was overall thinner in males than females in the cognitively normal group, and likewise, the differences due to sex were reduced in the MCI and AD groups. These findings were sustained after including cerebrospinal fluid (CSF) Tau and phosphorylated tau (pTau) as additional covariates.
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Archetti D, Young AL, Oxtoby NP, Ferreira D, Mårtensson G, Westman E, Alexander DC, Frisoni GB, Redolfi A. Inter-Cohort Validation of SuStaIn Model for Alzheimer's Disease. Front Big Data 2021; 4:661110. [PMID: 34095821 PMCID: PMC8173213 DOI: 10.3389/fdata.2021.661110] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 05/04/2021] [Indexed: 01/15/2023] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer’s disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting.
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Affiliation(s)
- Damiano Archetti
- Laboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Alexandra L Young
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.,Department of Computer Science, UCL Centre for Medical Image Computing, London, United Kingdom
| | - Neil P Oxtoby
- Department of Computer Science, UCL Centre for Medical Image Computing, London, United Kingdom
| | - Daniel Ferreira
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.,Department of Radiology, Mayo Clinic, Rochester, MN, United States
| | - Gustav Mårtensson
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Eric Westman
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Daniel C Alexander
- Department of Computer Science, UCL Centre for Medical Image Computing, London, United Kingdom
| | - Giovanni B Frisoni
- Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.,Laboratory of Alzheimer's Neuroimaging and Epidemiology - LANE, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Alberto Redolfi
- Laboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
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Quality control strategies for brain MRI segmentation and parcellation: Practical approaches and recommendations - insights from the Maastricht study. Neuroimage 2021; 237:118174. [PMID: 34000406 DOI: 10.1016/j.neuroimage.2021.118174] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/03/2021] [Accepted: 05/13/2021] [Indexed: 12/19/2022] Open
Abstract
Quality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control strategies are the current gold standard, although these may be unfeasible for large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents consensus in the appropriate quality control strategy to use. This study aimed to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies on the reduction of the measurement error. Structural brain MRI from 259 participants of The Maastricht Study were used. Morphological estimates were automatically extracted using FreeSurfer 6.0. Segmentations with inaccuracies were manually edited, and morphological estimates were compared before and after editing. In parallel, 12 quality control strategies were applied to the full sample. Those included: two manual strategies, in which images were visually inspected and either excluded or manually edited; five automated strategies, where outliers were excluded based on the tools "MRIQC" and "Qoala-T", and the metrics "morphological global measures", "Euler numbers" and "Contrast-to-Noise ratio"; and five semi-automated strategies, where the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. In order to quantify the effects of each quality control strategy, the proportion of unexplained variance relative to the total variance was extracted after the application of each strategy, and the resulting differences compared. Manually editing brain surfaces produced particularly large changes in subcortical brain volumes and moderate changes in cortical surface area, thickness and hippocampal volumes. The performance of the quality control strategies depended on the morphological measure of interest. Overall, manual quality control strategies yielded the largest reduction in relative unexplained variance. The best performing automated alternatives were those based on Euler numbers and MRIQC scores. The exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance. Manual quality control strategies are the most reliable solution for quality control of brain segmentation and parcellation. However, measures must be taken to prevent the subjectivity associated with these strategies. The detection of inaccurate segmentations based on Euler numbers or MRIQC provides a time efficient and reproducible alternative. The exclusion of outliers based on global morphological estimates must be avoided.
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Mielke MM. Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers. J Appl Lab Med 2021; 5:158-169. [PMID: 31811073 DOI: 10.1373/jalm.2019.030023] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/23/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND The development of cerebrospinal fluid and blood-based biomarkers for Alzheimer disease (AD) and related disorders is rapidly progressing. Such biomarkers may be used clinically to screen the population, to enhance diagnosis, or to help determine prognosis. Although the use of precision medicine methods has contributed to enhanced understanding of the AD pathophysiological changes and development of assays, one aspect not commonly considered is sex differences. CONTENT There are several ways in which sex can affect the concentration or interpretation of biofluid biomarkers. For some markers, concentrations will vary by sex. For others, the concentrations might not vary by sex, but the impact or interpretation may vary by sex depending on the context of use (e.g., diagnostic vs prognostic). Finally, for others, there will be no sex differences in concentrations or their interpretation. This review will first provide a basis for sex differences, including differences in brain structure and function, and the means by which these differences could contribute to sex differences in biomarker concentrations. Next, the current state of sex differences in AD-related biofluid markers (i.e., amyloid-β, phosphorylated τ, total τ, neurofilament light chain, and neurogranin) will be reviewed. Lastly, factors that can lead to the misinterpretation of observed sex differences in biomarkers (either providing evidence for or against) will be considered. SUMMARY This review is intended to provide an impetus to consider sex differences in the measurement and interpretation of AD-related biofluid-based biomarkers.
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Affiliation(s)
- Michelle M Mielke
- Departments of Health Sciences Research and Neurology, Mayo Clinic, Rochester, MN
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Abstract
Cortical morphological networks (CMN), where each network models the relationship in morphology between different cortical brain regions quantified using a specific measurement (e.g., cortical thickness), have not been investigated with respect to gender differences in the human brain. Cortical processes are expected to involve complex interactions between different brain regions, univariate methods thus might overlook informative gender markers. Hence, by leveraging machine learning techniques with the potential to highlight multivariate interacting effects, we found that the most discriminative CMN connections between males and females were derived from the left hemisphere using the mean sulcal depth as measurement. However, for both left and right hemispheres, the first most discriminative morphological connection revealed across all cortical attributes involved (entorhinal cortex ↔ caudal anterior cingulate cortex) and (entorhinal cortex ↔ transverse temporal cortex) respectively, which gives us new insights into behavioral gender differences from an omics perspective and might explain why males and females learn differently.
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Affiliation(s)
- Ahmed Nebli
- BASIRA Lab, Faculty of Computer and Informatics, Istanbul Technical University, Istanbul, Turkey.,Higher Institute of Applied Science and Technologies (ISSAT), University of Sousse, Sousse, Tunisia
| | - Islem Rekik
- BASIRA Lab, Faculty of Computer and Informatics, Istanbul Technical University, Istanbul, Turkey. .,Computing, School of Science and Engineering, University of Dundee, Dundee, UK.
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Biegon A. Considering Biological Sex in Traumatic Brain Injury. Front Neurol 2021; 12:576366. [PMID: 33643182 PMCID: PMC7902907 DOI: 10.3389/fneur.2021.576366] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 01/08/2021] [Indexed: 11/23/2022] Open
Abstract
Published epidemiological studies of traumatic brain injury (TBI) of all severities consistently report higher incidence in men. Recent increases in the participation of women in sports and active military service as well as increasing awareness of the very large number of women who sustain but do not report TBI as a result of intimate partner violence (IPV) suggest that the number of women with TBI is significantly larger than previously believed. Women are also grossly under-represented in clinical and natural history studies of TBI, most of which include relatively small numbers of women, ignore the role of sex- and age-related gonadal hormone levels, and report conflicting results. The emerging picture from recent studies powered to detect effects of biological sex as well as age (as a surrogate of hormonal status) suggest young (i.e., premenopausal) women are more likely to die from TBI relative to men of the same age group, but this is reversed in the 6th and 7th decades of life, coinciding with postmenopausal status in women. New data from concussion studies in young male and female athletes extend this finding to mild TBI, since female athletes who sustained mild TBI are significantly more likely to report more symptoms than males. Studies including information on gonadal hormone status at the time of injury are still too scarce and small to draw reliable conclusions, so there is an urgent need to include biological sex and gonadal hormone status in the design and analysis of future studies of TBI.
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Affiliation(s)
- Anat Biegon
- Department of Radiology and Neurology, Stony Brook University School of Medicine, Stony Brook, NY, United States
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Murata J, Murata S, Kodama T, Nakano H, Soma M, Nakae H, Satoh Y, Kogo H, Umeki N. Age-Related Changes in the Response of Finger Skin Blood Flow during a Braille Character Discrimination Task. Healthcare (Basel) 2021; 9:healthcare9020143. [PMID: 33535715 PMCID: PMC7912848 DOI: 10.3390/healthcare9020143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 11/16/2022] Open
Abstract
We hypothesized that age-related changes in sensory function might be reflected by a modulation of the blood flow response associated with tactile sensation. The aim of the present study was to clarify how the blood flow response of the fingers during concentrated finger perception is affected by aging. We measured the tactile-pressure threshold of the distal palmar pad of the index finger and skin blood flow in the finger (SBF) during Braille reading performed under blind conditions in young (n = 27) and older (n = 37) subjects. As a result, the tactile-pressure threshold was higher in older subjects (2.99 ± 0.37 log10 0.1 mg) than in young subjects (2.76 ± 0.24 log10 0.1 mg) (p < 0.01). On the other hand, the SBF response was markedly smaller in older subjects (−4.9 ± 7.0%) than in young subjects (−25.8 ± 15.4%) (p < 0.01). Moreover, the peak response arrival times to Braille reading in older and young subjects were 12.5 ± 3.1 s and 8.8 ± 3.6 s, respectively (p < 0.01). A decline in tactile sensitivity occurs with aging. Blood flow responses associated with tactile sensation are also affected by aging, as represented by a decrease in blood flow and a delay in the reaction time.
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Affiliation(s)
- Jun Murata
- Department of Physical and Occupational Therapy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8520, Japan; (H.K.); (N.U.)
- Correspondence: ; Tel.: +81-95-819-7923
| | - Shin Murata
- Department of Physical Therapy, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan; (S.M.); (T.K.); (H.N.)
| | - Takayuki Kodama
- Department of Physical Therapy, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan; (S.M.); (T.K.); (H.N.)
| | - Hideki Nakano
- Department of Physical Therapy, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan; (S.M.); (T.K.); (H.N.)
| | - Masayuki Soma
- Course of Rehabilitation, Department of Health Sciences, Tohoku Fukushi University, Miyagi 981-8522, Japan; (M.S.); (H.N.); (Y.S.)
| | - Hideyuki Nakae
- Course of Rehabilitation, Department of Health Sciences, Tohoku Fukushi University, Miyagi 981-8522, Japan; (M.S.); (H.N.); (Y.S.)
| | - Yousuke Satoh
- Course of Rehabilitation, Department of Health Sciences, Tohoku Fukushi University, Miyagi 981-8522, Japan; (M.S.); (H.N.); (Y.S.)
| | - Haruki Kogo
- Department of Physical and Occupational Therapy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8520, Japan; (H.K.); (N.U.)
| | - Naho Umeki
- Department of Physical and Occupational Therapy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8520, Japan; (H.K.); (N.U.)
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Saleh MAA, de Lange ECM. Impact of CNS Diseases on Drug Delivery to Brain Extracellular and Intracellular Target Sites in Human: A "WHAT-IF" Simulation Study. Pharmaceutics 2021; 13:95. [PMID: 33451111 PMCID: PMC7828633 DOI: 10.3390/pharmaceutics13010095] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 01/05/2021] [Accepted: 01/08/2021] [Indexed: 12/23/2022] Open
Abstract
The blood-brain barrier (BBB) is equipped with unique physical and functional processes that control central nervous system (CNS) drug transport and the resulting concentration-time profiles (PK). In CNS diseases, the altered BBB and CNS pathophysiology may affect the CNS PK at the drug target sites in the brain extracellular fluid (brainECF) and intracellular fluid (brainICF) that may result in changes in CNS drug effects. Here, we used our human CNS physiologically-based PK model (LeiCNS-PK3.0) to investigate the impact of altered cerebral blood flow (CBF), tight junction paracellular pore radius (pararadius), brainECF volume, and pH of brainECF (pHECF) and of brainICF (pHICF) on brainECF and brainICF PK for 46 small drugs with distinct physicochemical properties. LeiCNS-PK3.0 simulations showed a drug-dependent effect of the pathophysiological changes on the rate and extent of BBB transport and on brainECF and brainICF PK. Altered pararadius, pHECF, and pHICF affected both the rate and extent of BBB drug transport, whereas changes in CBF and brainECF volume modestly affected the rate of BBB drug transport. While the focus is often on BBB paracellular and active transport processes, this study indicates that also changes in pH should be considered for their important implications on brainECF and brainICF target site PK.
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Affiliation(s)
| | - Elizabeth C. M. de Lange
- Division of Systems Biomedicine and Pharmacology, Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands;
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Li H, Wang T, Zhang C, Su D, Lai Y, Sun B, Li D, Wu Y. Asleep Deep Brain Stimulation in Patients With Isolated Dystonia: Stereotactic Accuracy, Efficacy, and Safety. Neuromodulation 2020; 24:272-278. [PMID: 33325608 DOI: 10.1111/ner.13341] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 11/17/2020] [Accepted: 11/17/2020] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Lead placement for deep brain stimulation (DBS) is routinely performed using neuroimaging or microelectrode recording (MER). Recent studies have demonstrated that DBS under general anesthesia using an imaging-guided target technique ("asleep" DBS) can be performed accurately and effectively with lower surgery complication rates than the MER-guided target method under local anesthesia ("awake" DBS). This suggests that asleep DBS may be a more acceptable method. However, there is limited direct evidence focused on isolated dystonia using this method. Therefore, this study aimed to investigate the clinical outcomes and targeting accuracy in patients with dystonia who underwent asleep DBS. MATERIALS AND METHODS We examined 56 patients (112 leads) with isolated dystonia who underwent asleep DBS targeting in the globus pallidus internus (GPi) and subthalamic nucleus (STN). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were assessed preoperatively and at 12-month follow-up (12 m-FU). The lead accuracy was evaluated by comparing the coordinates of the preoperative plan with those of the final electrode implantation location. Other measures analyzed included stimulation parameters and adverse events (AEs). RESULTS For both GPi and STN cohorts, mean BFMDRS motor scores were significantly lower at 12 m-FU (8.9 ± 10.9 and 4.6 ± 5.7 points) than at baseline (22.6 ± 16.4 and 16.1 ± 14.1 points, p < 0.001). The mean difference between the planned target and the distal contact of the leads was 1.33 ± 0.54 mm for the right brain electrodes and 1.50 ± 0.57 mm for the left, determined by Euclidian distance. No perioperative complications or AEs related to the device were observed during the complete follow-up. However, AEs associated with stimulation occurred in 12 and 6 patients in the GPi and STN groups, respectively. CONCLUSIONS Asleep DBS may be an accurate, effective, and safe method for treating patients with isolated dystonia regardless of the stimulation target.
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Affiliation(s)
- Hongxia Li
- Department of Neurology & Institute of Neurology, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Wang
- Department of Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Center for Functional Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chencheng Zhang
- Department of Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Center for Functional Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Daoqing Su
- Department of Neurosurgery, Liaocheng People's Hospital and Liaocheng Clinical School of Shandong First Medical University, Liaocheng, China
| | - Yijie Lai
- Department of Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Center for Functional Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bomin Sun
- Department of Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Center for Functional Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dianyou Li
- Department of Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Center for Functional Neurosurgery, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yiwen Wu
- Department of Neurology & Institute of Neurology, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Sex differences in health and disease: A review of biological sex differences relevant to cancer with a spotlight on glioma. Cancer Lett 2020; 498:178-187. [PMID: 33130315 DOI: 10.1016/j.canlet.2020.07.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 07/16/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022]
Abstract
The influence of biological sex differences on human health and disease, while being increasingly recognized, has long been underappreciated and underexplored. While humans of all sexes are more alike than different, there is evidence for sex differences in the most basic aspects of human biology and these differences have consequences for the etiology and pathophysiology of many diseases. In a disease like cancer, these consequences manifest in the sex biases in incidence and outcome of many cancer types. The ability to deliver precise, targeted therapies to complex cancer cases is limited by our current understanding of the underlying sex differences. Gaining a better understanding of the implications and interplay of sex differences in diseases like cancer will thus be informative for clinical practice and biological research. Here we review the evidence for a broad array of biological sex differences in humans and discuss how these differences may relate to observed sex differences in various diseases, including many cancers and specifically glioblastoma. We focus on areas of human biology that play vital roles in healthy and disease states, including metabolism, development, hormones, and the immune system, and emphasize that the intersection of sex differences in these areas should not go overlooked. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.
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Soldati M, Murakami T, Laakso I. Inter-individual variations in electric fields induced in the brain by exposure to uniform magnetic fields at 50 Hz. Phys Med Biol 2020; 65:215006. [PMID: 32615544 DOI: 10.1088/1361-6560/aba21e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines and the Institute of Electrical and Electronics Engineers (IEEE) standard establish safety limits for human exposure to electromagnetic fields. At low frequencies, only a limited number of computational body models or simplified geometrical shapes are used to relate the internal induced electric fields and the external magnetic fields. As a consequence, both standard/guidelines derive the exposure reference levels for the external magnetic field without considering the variability between individuals. Here we provide quantitative data on the variation of the maximum electric field strengths induced in the brain of 118 individuals when exposed to uniform magnetic fields at 50 Hz. We found that individual characteristics, such as age and skull volume, as well as incident magnetic field direction, have a systematic effect on the peak electric field values. Older individuals show higher induced electric field strengths, possibly due to age-related anatomical changes in brain. Peak electric field strengths are found to increase for larger skull volumes, as well as for incident magnetic fields directed along the lateral direction. Moreover, the maximum electric fields provided by the anatomical models used by ICNIRP for deriving exposure limits are considerably higher than those obtained here. On the contrary, the IEEE elliptical exposure model produces a weaker peak electric field strength. Our findings are useful for the revision and harmonization of the current exposure standard and guidelines. The present investigation reduces the dosimetric uncertainty of the induced electric field among different anatomical induction models. The obtained results can be used as a basis for the selection of appropriate reduction factors when deriving exposure reference levels for human protection to low-frequency electromagnetic exposure.
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Affiliation(s)
- Marco Soldati
- Department of Electrical Engineering and Automation, Aalto University, Espoo, Finland
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Adversarial brain multiplex prediction from a single brain network with application to gender fingerprinting. Med Image Anal 2020; 67:101843. [PMID: 33129149 DOI: 10.1016/j.media.2020.101843] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 07/25/2020] [Accepted: 09/07/2020] [Indexed: 11/22/2022]
Abstract
Brain connectivity networks, derived from magnetic resonance imaging (MRI), non-invasively quantify the relationship in function, structure, and morphology between two brain regions of interest (ROIs) and give insights into gender-related connectional differences. However, to the best of our knowledge, studies on gender differences in brain connectivity were limited to investigating pairwise (i.e., low-order) relationships across ROIs, overlooking the complex high-order interconnectedness of the brain as a network. A few recent works on neurological disorders addressed this limitation by introducing the brain multiplex which is composed of a source network intra-layer, a target intra-layer, and a convolutional interlayer capturing the high-level relationship between both intra-layers. However, brain multiplexes are built from at least two different brain networks hindering their application to connectomic datasets with single brain networks (e.g., functional networks). To fill this gap, we propose Adversarial Brain Multiplex Translator (ABMT), the first work for predicting brain multiplexes from a source network using geometric adversarial learning to investigate gender differences in the human brain. Our framework comprises: (i) a geometric source to target network translator mimicking a U-Net architecture with skip connections, (ii) a conditional discriminator which distinguishes between predicted and ground truth target intra-layers, and finally (iii) a multi-layer perceptron (MLP) classifier which supervises the prediction of the target multiplex using the subject class label (e.g., gender). Our experiments on a large dataset demonstrated that predicted multiplexes significantly boost gender classification accuracy compared with source networks and unprecedentedly identify both low and high-order gender-specific brain multiplex connections. Our ABMT source code is available on GitHub at https://github.com/basiralab/ABMT.
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Cheng CH, Koo BB, Calderazzo S, Quinn E, Aenlle K, Steele L, Klimas N, Krengel M, Janulewicz P, Toomey R, Michalovicz LT, Kelly KA, Heeren T, Little D, O’Callaghan JP, Sullivan K. Alterations in high-order diffusion imaging in veterans with Gulf War Illness is associated with chemical weapons exposure and mild traumatic brain injury. Brain Behav Immun 2020; 89:281-290. [PMID: 32745586 PMCID: PMC7755296 DOI: 10.1016/j.bbi.2020.07.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/11/2020] [Accepted: 07/08/2020] [Indexed: 01/02/2023] Open
Abstract
The complex etiology behind Gulf War Illness (GWI) has been attributed to the combined exposure to neurotoxicant chemicals, brain injuries, and some combat experiences. Chronic GWI symptoms have been shown to be associated with intensified neuroinflammatory responses in animal and human studies. To investigate the neuroinflammatory responses and potential causes in Gulf War (GW) veterans, we focused on the effects of chemical/biological weapons (CBW) exposure and mild traumatic brain injury (mTBI) during the war. We applied a novel MRI diffusion processing method, Neurite density imaging (NDI), on high-order diffusion imaging to estimate microstructural alterations of brain imaging in Gulf War veterans with and without GWI, and collected plasma proinflammatory cytokine samples as well as self-reported health symptom scores. Our study identified microstructural changes specific to GWI in the frontal and limbic regions due to CBW and mTBI, and further showed distinctive microstructural patterns such that widespread changes were associated with CBW and more focal changes on diffusion imaging were observed in GW veterans with an mTBI during the war. In addition, microstructural alterations on brain imaging correlated with upregulated blood proinflammatory cytokine markers TNFRI and TNFRII and with worse outcomes on self-reported symptom measures for fatigue and sleep functioning. Taken together, these results suggest TNF signaling mediated inflammation affects frontal and limbic regions of the brain, which may contribute to the fatigue and sleep symptoms of the disease and suggest a strong neuroinflammatory component to GWI. These results also suggest exposures to chemical weapons and mTBI during the war are associated with different patterns of peripheral and central inflammation and highlight the brain regions vulnerable to further subtle microscale morphological changes and chronic signaling to nearby glia.
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Affiliation(s)
| | - Bang-Bon Koo
- School of Medicine, Boston University, Boston, MA, US
| | | | - Emily Quinn
- School of Public Health, Boston University, Boston MA USA
| | - Kristina Aenlle
- Nova Southeastern University, Fort Lauderdale, FL, USA
- Department of Veterans Affairs, Miami VA Healthcare System, Research Service, Miami, FL, USA
| | - Lea Steele
- Baylor College of Medicine, Houston, TX, USA
| | - Nancy Klimas
- Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Maxine Krengel
- School of Public Health, Boston University, Boston MA USA
| | | | | | - Lindsay T. Michalovicz
- Health Effects Laboratory Division, Center for Disease Control and Prevention – National Institute for Occupational Safety and Health, Morgantown, WV, USA
| | - Kimberly A Kelly
- Health Effects Laboratory Division, Center for Disease Control and Prevention – National Institute for Occupational Safety and Health, Morgantown, WV, USA
| | - Timothy Heeren
- School of Public Health, Boston University, Boston MA USA
| | | | - James P. O’Callaghan
- Health Effects Laboratory Division, Center for Disease Control and Prevention – National Institute for Occupational Safety and Health, Morgantown, WV, USA
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49
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Abdolalizadeh A, Ostadrahimi H, Mohajer B, Darvishi A, Sattarian M, Bayani Ershadi AS, Abbasi N. White Matter Microstructural Properties Associated with Impaired Attention in Chronic Schizophrenia: A Multi-Center Study. Psychiatry Res Neuroimaging 2020; 302:111105. [PMID: 32498000 DOI: 10.1016/j.pscychresns.2020.111105] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 04/24/2020] [Accepted: 05/01/2020] [Indexed: 12/17/2022]
Abstract
Attention as a key cognitive function is impaired in schizophrenia, interfering with the normal daily life of the patients. Previous studies on the microstructural correlates of attention in schizophrenia were limited to single fibers, did not include a control group, or did not adjust for drug dosage. In the current study, we investigated the association between microstructural properties of the white matter fibers and attention tests in 81 patients and 79 healthy controls from the Mind Clinical Imaging Consortium database. Integrity measures of superior longitudinal fasciculus, cingulum, genu, and splenium were extracted after tractography. Using an interaction model between diagnosis and microstructural properties, and adjusting for age, gender, acquisition site, education, and cumulative drug usage dose, and after correcting for family-wise error, we showed decreased integrity in the patients and a significant negative association between fractional anisotropy of the tracts and trail making test part A with a greater expected decrease in the attention per unit of decrease of integrity in the patients compared to the healthy controls. Our findings suggest that decreased integrity of the bilateral cingulum, and splenium, are independent of the cumulative drug dosage, age, gender, and site, and may underlie the impaired attention in the schizophrenia.
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Affiliation(s)
| | - Hamidreza Ostadrahimi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahram Mohajer
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Asma Darvishi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahta Sattarian
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Nooshin Abbasi
- McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
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50
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Orlando A, Rubin B, Panchal R, Tanner A, Hudson J, Harken K, Madayag R, Berg G, Bar-Or D. In Patients Over 50 Years, Increased Age Is Associated With Decreased Odds of Documented Loss of Consciousness After a Concussion. Front Neurol 2020; 11:39. [PMID: 32082248 PMCID: PMC7005230 DOI: 10.3389/fneur.2020.00039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 01/10/2020] [Indexed: 12/28/2022] Open
Abstract
Background: Advanced aged adults have the highest rate of traumatic brain injury (TBI) related hospital admissions, compared to younger age groups. Data were published in 2014 indicating differential injury and neurological responses to a TBI by age categories. In a recent article examining patients with mTBI and isolated subdural hematoma, it was found that older patients had a decreased risk of documented loss of consciousness (LOC). The primary objective was to determine the extent to which the odds of documented LOC changes with increasing age in a population of older adults suffering an isolated concussion and uncomplicated mTBI. Methods: This was a retrospective study utilizing 6 years (2010–2015) of National Trauma Data Bank data. This study included patients with (1) diagnosis of concussion; (2) positive or negative loss of consciousness; (3) loss of consciousness durations no longer than 59 min or undefined; (4) age ≥50 years; (5) had a “fall” mechanism of injury; and (6) a valid emergency department Glasgow coma scale 13–15. We excluded patients (1) with any intracranial hemorrhage or intracranial injury of other and unspecified nature; (2) skull fracture; (3) an injury severity scale score >17; (4) a concussion with “unspecified” LOC (ICD-9: 850.9). Results: There were 7,466 patients included in the study; the median (IQR) age was 70 (60–80) years. The risk of documented LOC was 71% (n = 5,319). An 80-year-old had 72% decreased odds of having a documented LOC, compared to a 50-year-old (OR = 0.28, 99.5%CI [0.23–0.34], P < 0.001). This association held when controlling for multiple demographic, comorbid, and clinical variables, and in sensitivity analyses. Conclusion: These nationwide data suggest that in patients aged ≥50 years, a significant inverse association exists between age and odds of documented LOC after sustaining a fall-related concussion. Additional studies are needed to validate these findings and to investigate the triad of age, documented LOC, and intracranial hemorrhage. Clinical diagnostic criteria relying on LOC might be at risk of being modified by the association between increasing age and decreasing odds of LOC.
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Affiliation(s)
- Alessandro Orlando
- Department of Trauma Research, Swedish Medical Center, Englewood, CO, United States.,Department of Trauma Research, Penrose Hospital, Colorado Springs, CO, United States.,Department of Trauma Research, Medical City Plano, Plano, TX, United States.,Department of Trauma Research, St. Anthony Hospital, Lakewood, CO, United States.,Department of Trauma Research, Research Medical Center, Kansas City, MO, United States.,Department of Trauma Research, Wesley Medical Center, Wichita, KS, United States
| | - Benjamin Rubin
- Department of Neurosurgery, Swedish Medical Center, Englewood, CO, United States
| | - Ripul Panchal
- Department of Neurosurgery, Medical City Plano, Plano, TX, United States
| | - Allen Tanner
- Department of Trauma Services, Penrose Hospital, Colorado Springs, CO, United States
| | - John Hudson
- Department of Neurosurgery, St. Anthony Hospital, Lakewood, CO, United States
| | - Kyle Harken
- Department of Trauma Services, Research Medical Center, Kansas City, MO, United States
| | - Robert Madayag
- Department of Trauma Services, St. Anthony Hospital, Lakewood, CO, United States
| | - Gina Berg
- Department of Trauma Research, Wesley Medical Center, Wichita, KS, United States
| | - David Bar-Or
- Department of Trauma Research, Swedish Medical Center, Englewood, CO, United States.,Department of Trauma Research, Penrose Hospital, Colorado Springs, CO, United States.,Department of Trauma Research, Medical City Plano, Plano, TX, United States.,Department of Trauma Research, St. Anthony Hospital, Lakewood, CO, United States.,Department of Trauma Research, Research Medical Center, Kansas City, MO, United States.,Department of Trauma Research, Wesley Medical Center, Wichita, KS, United States
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