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McCrea M, Reddy N, Ghobrial K, Ahearn R, Krafty R, Hitchens TK, Martinez-Gonzalez J, Modo M. Mesoscale connectivity of the human hippocampus and fimbria revealed by ex vivo diffusion MRI. Neuroimage 2025; 310:121125. [PMID: 40101867 DOI: 10.1016/j.neuroimage.2025.121125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 02/26/2025] [Accepted: 03/05/2025] [Indexed: 03/20/2025] Open
Abstract
The human hippocampus is essential to cognition and emotional processing. Its function is defined by its connectivity. Although some pathways have been well-established, our knowledge about anterior-posterior connectivity and the distribution of fibers from major fiber bundles remains limited. Mesoscale (250 μm isotropic acquisition, upsampled to 125 μm) resolution MR images of the human temporal lobe afforded a detailed visualization of fiber tracts, including those that related anterior-posterior substructures defined as subregions (head, body, tail) and subfields (cornu ammonis 1-3, dentate gyrus) of the hippocampus. Fifty pathways were dissected between the head and body, highlighting an intricate mesh of connectivity between these two subregions. Along the body subregion, 12 lamellae were identified based on morphology and the presence of interlamellar fibers that appear to connect neighboring lamellae at the edge of the external limb of the granule cell layer (GCL). Translamellar fibers (i.e. longitudinal fibers crossing more than 2 lamellae) were also evident at the edge of the internal limb of the GCL. The dentate gyrus of the body was the main site of connectivity with the fimbria. Unique pathways were dissected within the fimbria that connected the body of the hippocampus with the amygdala and the temporal pole. A topographical segregation within the fimbria was determined by fibers' hippocampal origin, illustrating the importance of mapping the spatial distribution of fibers. Elucidating the detailed structural connectivity of the hippocampus is crucial to develop better diagnostic markers of neurological and psychiatric conditions, as well as to devise novel surgical interventions.
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Affiliation(s)
- Madeline McCrea
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | - Navya Reddy
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | - Kathryn Ghobrial
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | - Ryan Ahearn
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | - Ryan Krafty
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | - T Kevin Hitchens
- Neurobiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
| | | | - Michel Modo
- Departments of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, USA.
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Porcu M, Cocco L, Marrosu F, Cau R, Puig J, Suri JS, Saba L. Hippocampus and olfactory impairment in Parkinson disease: a comparative exploratory combined volumetric/functional MRI study. Neuroradiology 2024; 66:1941-1953. [PMID: 39046517 DOI: 10.1007/s00234-024-03436-6] [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: 03/29/2024] [Accepted: 07/18/2024] [Indexed: 07/25/2024]
Abstract
INTRODUCTION Patients with Parkinson's Disease (PD) commonly experience Olfactory Dysfunction (OD). Our exploratory study examined hippocampal volumetric and resting-state functional magnetic resonance imaging (rs-fMRI) variations in a Healthy Control (HC) group versus a cognitively normal PD group, further categorized into PD with No/Mild Hyposmia (PD-N/MH) and PD with Severe Hyposmia (PD-SH). METHODS We calculated participants' relative Total Hippocampal Volume (rTHV) and performed Spearman's partial correlations, controlled for age and gender, to examine the correlation between rTHV and olfactory performance assessed by the Odor Stick Identification Test for the Japanese (OSIT-J) score. Mann-Whitney U tests assessed rTHV differences across groups and subgroups, rejecting the null hypothesis for p < 0.05. Furthermore, a seed-based rs-fMRI analysis compared hippocampal connectivity differences using a one-way ANCOVA covariate model with controls for age and gender. RESULTS Spearman's partial correlations indicated a moderate positive correlation between rTHV and OSIT-J in the whole study population (ρ = 0.406; p = 0.007), PD group (ρ = 0.493; p = 0.008), and PD-N/MH subgroup (ρ = 0.617; p = 0.025). Mann-Whitney U tests demonstrated lower rTHV in PD-SH subgroup compared to both HC group (p = 0.013) and PD-N/MH subgroup (p = 0.029). Seed-to-voxel rsfMRI analysis revealed reduced hippocampal connectivity in PD-SH subjects compared to HC subjects with a single cluster of voxels. CONCLUSIONS Although the design of the study do not allow to make firm conclusions, it is reasonable to speculate that the progressive involvement of the hippocampus in PD patients is associated with the progression of OD.
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Affiliation(s)
- Michele Porcu
- Department of Radiology, AOU Cagliari, University of Cagliari, Cagliari, Italy.
- Department of Medical Imaging, Azienda Ospedaliera Universitaria di Cagliari, S.S. 554, km 4.500, CAP 09042, Monserrato (Cagliari), Italy.
| | - Luigi Cocco
- Department of Radiology, AOU Cagliari, University of Cagliari, Cagliari, Italy
| | - Francesco Marrosu
- Department of Radiology, AOU Cagliari, University of Cagliari, Cagliari, Italy
| | - Riccardo Cau
- Department of Radiology, AOU Cagliari, University of Cagliari, Cagliari, Italy
| | - Josep Puig
- Department of Radiology (IDI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain
| | - Jasjit S Suri
- Stroke Monitoring and Diagnostic Division, AtheroPoint™, Roseville, CA, USA
| | - Luca Saba
- Department of Radiology, AOU Cagliari, University of Cagliari, Cagliari, Italy
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Loenneker HD, Artemenko C, Willmes K, Liepelt-Scarfone I, Nuerk HC. Deficits in or Preservation of Basic Number Processing in Parkinson's Disease? A Registered Report. J Neurosci Res 2024; 102:e25397. [PMID: 39548739 DOI: 10.1002/jnr.25397] [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: 08/01/2024] [Revised: 10/16/2024] [Accepted: 10/27/2024] [Indexed: 11/18/2024]
Abstract
Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health care system. Until now, diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests mechanisms of both primary and secondary dyscalculia. The current study systematically investigated basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consisted of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients were stratified into patients with normal cognition (PD-NC) or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing was assessed using transcoding, number line estimation, and (non-) symbolic number magnitude comparison tasks. Discriminant analysis was employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants were subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Results indicate a profile of preserved (verbal representation) and impaired (magnitude representation, place × value activation) function in PD-MCI, hinting at basal ganglia dysfunction affecting numerical cognition in PD. Numerical deficits could not be explained by domain-general cognitive impairments, so that future research needs to incorporate domain-specific tasks of sufficient difficulty.
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Affiliation(s)
| | - Christina Artemenko
- Department of Psychology, University of Tuebingen, Tuebingen, Germany
- LEAD Graduate School & Research Network, University of Tuebingen, Tuebingen, Germany
| | - Klaus Willmes
- Department of Neurology, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Inga Liepelt-Scarfone
- Department of Clinical Neurodegeneration, Hertie Institute for Clinical Brain Research, Tuebingen, Germany
- German Centre for Neurodegenerative Diseases, Tuebingen, Germany
- IB-Hochschule für Gesundheit und Soziales, Stuttgart, Germany
| | - Hans-Christoph Nuerk
- Department of Psychology, University of Tuebingen, Tuebingen, Germany
- LEAD Graduate School & Research Network, University of Tuebingen, Tuebingen, Germany
- German Center for Mental Health, Tübingen, Germany
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Lu J, Xing X, Qu J, Wu J, Zheng M, Hua X, Xu J. Alterations of contralesional hippocampal subfield volumes and relations to cognitive functions in patients with unilateral stroke. Brain Behav 2024; 14:e3645. [PMID: 39135280 PMCID: PMC11319231 DOI: 10.1002/brb3.3645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 06/23/2024] [Accepted: 07/12/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.
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Affiliation(s)
- Juan‐Juan Lu
- School of Rehabilitation ScienceShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Xiang‐Xin Xing
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Jiao Qu
- Department of RadiologyShanghai Songjiang District Central HospitalShanghaiChina
| | - Jia‐Jia Wu
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Mou‐Xiong Zheng
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Xu‐Yun Hua
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Jian‐Guang Xu
- School of Rehabilitation ScienceShanghai University of Traditional Chinese MedicineShanghaiChina
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- Engineering Research Center of Traditional Chinese Medicine Intelligent RehabilitationMinistry of EducationShanghaiChina
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Kumari S, Rana B, Senthil Kumaran S, Chaudhary S, Jain S, Srivastava AK, Rajan R. Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson's Disease. Neuroscience 2024; 551:217-228. [PMID: 38843989 DOI: 10.1016/j.neuroscience.2024.05.029] [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: 03/27/2024] [Revised: 05/16/2024] [Accepted: 05/23/2024] [Indexed: 06/15/2024]
Abstract
INTRODUCTION Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. METHODS We investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. RESULTS AND DISCUSSION In PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. CONCLUSION Unilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.
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Affiliation(s)
- Sadhana Kumari
- Department of NMR, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Bharti Rana
- Department of Computer Science, University of Delhi, Delhi 110007, India
| | - S Senthil Kumaran
- Department of NMR, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
| | - Shefali Chaudhary
- Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
| | - Suman Jain
- Department of Physiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Achal Kumar Srivastava
- Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Roopa Rajan
- Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
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Tarhan M, Atalay B, Buz Yaşar A, Özdilek FB. Exploring the cognitive assessment potential of MRI-based volumetric hippocampal segmentation in Parkinson's disease. Brain Behav 2024; 14:e3576. [PMID: 38970157 PMCID: PMC11226409 DOI: 10.1002/brb3.3576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 05/13/2024] [Accepted: 05/15/2024] [Indexed: 07/08/2024] Open
Abstract
PURPOSE To investigate the potential of magnetic resonance imaging (MRI)-based total and segmental hippocampus volume analysis in the assessment of cognitive status in Parkinson's disease (PD). METHODS We divided participants into three groups Group A-Parkinson patients (Pp) with normal cognitive status (n = 25), Group B-Pp with dementia (n = 17), and Group C-healthy controls (n = 37). Three-dimensional T1W Fast Spoiled Gradient Recalled Echo images were used for Volbrain hippocampus subfield segmentation. We used the "Winterburn" protocol, which divides the hippocampus into five segments, Cornu Ammonis (CA),CA2/CA3, CA4/dentate gyrus, stratum radiatum, lacunosum, and moleculare, and subiculum. RESULTS A total of 79 participants were included in the study, consisting of 42 individuals with PD (64.2% male) and 37 healthy controls (54.1% male). The mean age of PD was 60.9 ± 10.7 years and the mean age of control group was 59.27 ± 12.3 years. Significant differences were found in total hippocampal volumes between Group A and B (p = .047. Statistically significant group differences were found in total, right, and left CA1 volumes (analysis of variance [ANOVA]: F(2,76) = 8.098, p = .001; F(2,76) = 7.628, p = .001; F(2,76) = 5.084, p = .008, respectively), as well as in total subiculum volumes (ANOVA: F(2,76) = 4.368, p = .016). Post hoc tests showed that total subiculum volume was significantly lower in individuals with normal cognitive status (0.474 ± 0.116 cm3) compared to healthy controls (0.578 ± 0.151 cm3, p = .013). CONCLUSION Volumetric hippocampal MRI can be used to assess the cognitive status of Pp. Longitudinal studies that evaluate Pp who progress from normal cognition to dementia are required to establish a causal relationship.
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Affiliation(s)
- Merve Tarhan
- Department of RadiologyIstanbul Medeniyet University Göztepe Training and Research HospitalIstanbulTurkey
| | - Başak Atalay
- Department of RadiologyIstanbul Medeniyet University Göztepe Training and Research HospitalIstanbulTurkey
| | | | - Fatma Betül Özdilek
- Department of NeurologyIstanbul Medeniyet University Göztepe Training and Research HospitalIstanbulTurkey
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Yang Q, Chen G, Yang Z, Raviv TR, Gao Y. Fine hippocampal morphology analysis with a multi-dataset cross-sectional study on 2911 subjects. Neuroimage Clin 2024; 43:103620. [PMID: 38823250 PMCID: PMC11168486 DOI: 10.1016/j.nicl.2024.103620] [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: 12/19/2023] [Revised: 05/07/2024] [Accepted: 05/18/2024] [Indexed: 06/03/2024]
Abstract
CA1 subfield and subiculum of the hippocampus contain a series of dentate bulges, which are also called hippocampus dentation (HD). There have been several studies demonstrating an association between HD and brain disorders. Such as the number of hippocampal dentation correlates with temporal lobe epilepsy. And epileptic hippocampus have a lower number of dentation compared to contralateral hippocampus. However, most studies rely on subjective assessment by manual searching and counting in HD areas, which is time-consuming and labor-intensive to process large amounts of samples. And to date, only one objective method for quantifying HD has been proposed. Therefore, to fill this gap, we developed an automated and objective method to quantify HD and explore its relationship with neurodegenerative diseases. In this work, we performed a fine-scale morphological characterization of HD in 2911 subjects from four different cohorts of ADNI, PPMI, HCP, and IXI to quantify and explore differences between them in MR T1w images. The results showed that the degree of right hippocampal dentation are lower in patients with Alzheimer's disease than samples in mild cognitive impairment or cognitively normal, whereas this change is not significant in Parkinson's disease progression. The innovation of this paper that we propose a quantitative, robust, and fully automated method. These methodological innovation and corresponding results delineated above constitute the significance and novelty of our study. What's more, the proposed method breaks through the limitations of manual labeling and is the first to quantitatively measure and compare HD in four different brain populations including thousands of subjects. These findings revealed new morphological patterns in the hippocampal dentation, which can help with subsequent fine-scale hippocampal morphology research.
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Affiliation(s)
- Qinzhu Yang
- School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
| | - Guojing Chen
- School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
| | - Zhi Yang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Tammy Riklin Raviv
- The School of Electrical and Computer Engineering, Ben-Gurion University of the Negev, Be'er Sheva, Israel
| | - Yi Gao
- School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, China; Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen, China; Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, China.
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Cao J, Tang Y, Chen S, Yu S, Wan K, Yin W, Zhen W, Zhao W, Zhou X, Zhu X, Sun Z. The Hippocampal Subfield Volume Reduction and Plasma Biomarker Changes in Mild Cognitive Impairment and Alzheimer's Disease. J Alzheimers Dis 2024; 98:907-923. [PMID: 38489180 DOI: 10.3233/jad-231114] [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] [Indexed: 03/17/2024]
Abstract
Background The hippocampus consists of histologically and functionally distinct subfields, which shows differential vulnerabilities to Alzheimer's disease (AD)-associated pathological changes. Objective To investigate the atrophy patterns of the main hippocampal subfields in patients with mild cognitive impairment (MCI) and AD and the relationships among the hippocampal subfield volumes, plasma biomarkers and cognitive performance. Methods This cross-sectional study included 119 patients stratified into three categories: normal cognition (CN; N = 40), MCI (N = 39), and AD (N = 40). AD-related plasma biomarkers were measured, including amyloid-β (Aβ)42, Aβ40, Aβ42/Aβ40 ratio, p-tau181, and p-tau217, and the hippocampal subfield volumes were calculated using automated segmentation and volumetric procedures implemented in FreeSurfer. Results The subiculum body, cornu ammonis (CA) 1-head, CA1-body, CA4-body, molecular_layer_HP-head, molecular_layer_HP-body, and GC-ML-DG-body volumes were smaller in the MCI group than in the CN group. The subiculum body and CA1-body volumes accurately distinguished MCI from CN (area under the curve [AUC] = 0.647-0.657). The subiculum-body, GC-ML-DG-body, CA4-body, and molecular_layer_HP-body volumes accurately distinguished AD from MCI (AUC = 0.822-0.833) and AD from CN (AUC = 0.903-0.905). The p-tau 217 level served as the best plasma indicator of AD and correlated with broader hippocampal subfield volumes. Moreover, mediation analysis demonstrated that the subiculum-body volume mediated the associations between the p-tau217 and p-tau181 levels, and the Montreal Cognitive Assessment and Auditory Verbal Learning Test recognition scores. Conclusions Hippocampal subfields with distinctive atrophy patterns may mediate the effects of tau pathology on cognitive function. The subiculum-body may be the most clinically meaningful hippocampal subfield, which could be an effective target region for assessing disease progression.
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Affiliation(s)
- Jing Cao
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yating Tang
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Shujian Chen
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Siqi Yu
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ke Wan
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wenwen Yin
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wenhui Zhen
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wenming Zhao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xia Zhou
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiaoqun Zhu
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhongwu Sun
- Department of Neurology, Th First Affiliated Hospital of Anhui Medical University, Hefei, China
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Modo M, Sparling K, Novotny J, Perry N, Foley LM, Hitchens TK. Mapping mesoscale connectivity within the human hippocampus. Neuroimage 2023; 282:120406. [PMID: 37827206 PMCID: PMC10623761 DOI: 10.1016/j.neuroimage.2023.120406] [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: 07/07/2023] [Revised: 09/28/2023] [Accepted: 10/10/2023] [Indexed: 10/14/2023] Open
Abstract
The connectivity of the hippocampus is essential to its functions. To gain a whole system view of intrahippocampal connectivity, ex vivo mesoscale (100 μm isotropic resolution) multi-shell diffusion MRI (11.7T) and tractography were performed on entire post-mortem human right hippocampi. Volumetric measurements indicated that the head region was largest followed by the body and tail regions. A unique anatomical organization in the head region reflected a complex organization of the granule cell layer (GCL) of the dentate gyrus. Tractography revealed the volumetric distribution of the perforant path, including both the tri-synaptic and temporoammonic pathways, as well as other well-established canonical connections, such as Schaffer collaterals. Visualization of the perforant path provided a means to verify the borders between the pro-subiculum and CA1, as well as between CA1/CA2. A specific angularity of different layers of fibers in the alveus was evident across the whole sample and allowed a separation of afferent and efferent connections based on their origin (i.e. entorhinal cortex) or destination (i.e. fimbria) using a cluster analysis of streamlines. Non-canonical translamellar connections running along the anterior-posterior axis were also discerned in the hilus. In line with "dentations" of the GCL, mossy fibers were bunching together in the sagittal plane revealing a unique lamellar organization and connections between these. In the head region, mossy fibers projected to the origin of the fimbria, which was distinct from the body and tail region. Mesoscale tractography provides an unprecedented systems view of intrahippocampal connections that underpin cognitive and emotional processing.
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Affiliation(s)
- Michel Modo
- Department of Radiology; Department of BioEngineering; McGowan Institute for Regenerative Medicine; Centre for Neuroscience University of Pittsburgh (CNUP); Centre for the Neural Basis of Cognition (CNBC).
| | | | | | | | | | - T Kevin Hitchens
- Small Animal Imaging Center; Departmnet of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15203, USA
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Zheng X, Lin Y, Huang L, Lin X. Effect of lidocaine on cognitively impaired rats: Anti-inflammatory and antioxidant mechanisms in combination with CRMP2 antiphosphorylation. Immun Inflamm Dis 2023; 11:e1040. [PMID: 37904712 PMCID: PMC10566448 DOI: 10.1002/iid3.1040] [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: 04/29/2023] [Revised: 09/11/2023] [Accepted: 09/20/2023] [Indexed: 11/01/2023] Open
Abstract
OBJECTIVE Studies have shown that lidocaine has antioxidative stress, anti-inflammatory, and nerve-protective effects. The current study investigated the effects of lidocaine on cognitive function in rats with cognitive dysfunction. METHODS A total of 48 rats were randomly assigned to four groups of 12 rats each: control group; L (lidocaine) + D (d-galactose) group, d-galactose group (D group); and D + L group. We assessed cognitive function using a Morris water maze (MWM) and pathologic changes of hippocampal sections. An enzyme-linked immunosorbent assay (ELIZA) was used to detect serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels in rats, and protein immunoblotting (western blot) was used to detect brain tissue proteins (collapsing response mediator protein-2 [CRMP2], phosphorylated-collapsing response mediator protein-2 [P-CRMP2], and β-amyloid protein [Aβ]). RESULTS The MWM showed that the d-gal group (284.09 ± 20.46, 5.20 ± 0.793) performed worse than the L + D (265.37 ± 22.34, 4.170 ± 0.577; p = .000) and D + L groups (254.72 ± 27.87, 3.750; p = .000) in escape latency and number of platform crossings, respectively. The L + D group (44.94 ± 2.92 pg/mL, 6.22 ± 0.50 pg/mL, and 460.02 ± 8.26 nmol/mL) and D + L group (46.88 ± 2.63 pg/mL, 5.90 ± 0.38 pg/mL, and 465.6 ± 16.07 nmol/mL) had significantly lower serum inflammatory levels of interleukin-6, tumor necrosis factor-α, and MDA than the d-gal group (57.79 ± 3.96 pg/mL, 11.25 ± 1.70 pg/mL, and 564.9 ± 15.90 nmol/mL), respectively. The L + D group (3.17 ± 0.41 μg/mL) and D + L group (3.08 ± 0.09 μg/mL) had significantly higher serum inflammatory levels of SOD than the d-gal group (2.20 ± 0.13 μg/mL) (all p = .000). The levels of CRMP2, P-CRMP2, and Aβ in the brain tissue homogenates of the L + D group (0.87 ± 0.04, 0.57 ± 0.0, and 0.16 ± 0.02) and the D + L group (0.82 ± 0.05, 0.58 ± 0.09, and 0.15 ± 0.02) were significantly different than the d-gal group (0.67 ± 0.03, 0.96 ± 0.040, and 0.29 ± 0.05). CONCLUSIONS Lidocaine was shown to reduce cognitive impairment in rats with cognitive dysfunction through anti-inflammatory and antioxidative stress mechanisms in combination with CRMP2 antiphosphorylation.
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Affiliation(s)
- Xiaohong Zheng
- Department of Anesthesiology, First Affiliated HospitalFujian Medical UniversityFuzhouChina
- Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina
| | - Yuerong Lin
- Department of Anesthesiology, First Affiliated HospitalFujian Medical UniversityFuzhouChina
- Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina
| | - Linshen Huang
- Department of Anesthesiology, First Affiliated HospitalFujian Medical UniversityFuzhouChina
- Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina
| | - Xianzhong Lin
- Department of Anesthesiology, First Affiliated HospitalFujian Medical UniversityFuzhouChina
- Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina
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11
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Fama R, Müller-Oehring EM, Levine TF, Sullivan EV, Sassoon SA, Asok P, Brontë-Stewart HM, Poston KL, Pohl KM, Pfefferbaum A, Schulte T. Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates. Brain Struct Funct 2023; 228:845-858. [PMID: 37069296 PMCID: PMC10147801 DOI: 10.1007/s00429-023-02626-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/03/2023] [Indexed: 04/19/2023]
Abstract
Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.
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Affiliation(s)
- Rosemary Fama
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
| | - Eva M Müller-Oehring
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA.
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA.
| | - Taylor F Levine
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Edith V Sullivan
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA
| | - Stephanie A Sassoon
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
| | - Priya Asok
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
| | - Helen M Brontë-Stewart
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Kathleen L Poston
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Kilian M Pohl
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
| | - Adolf Pfefferbaum
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
| | - Tilman Schulte
- Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA
- Clinical Psychology, Palo Alto University, 1791 Arastradero Rd, Palo Alto, CA, 94304, USA
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12
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Xu H, Liu Y, Wang L, Zeng X, Xu Y, Wang Z. Role of hippocampal subfields in neurodegenerative disease progression analyzed with a multi-scale attention-based network. Neuroimage Clin 2023; 38:103370. [PMID: 36948139 PMCID: PMC10034639 DOI: 10.1016/j.nicl.2023.103370] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 02/15/2023] [Accepted: 03/03/2023] [Indexed: 03/17/2023]
Abstract
BACKGROUND AND OBJECTIVE Both Alzheimer's disease (AD) and Parkinson's disease (PD) are progressive neurodegenerative diseases. Early identification is very important for the prevention and intervention of their progress. Hippocampus plays a crucial role in cognition, in which there are correlations between atrophy of Hippocampal subfields and cognitive impairment in neurodegenerative diseases. Exploring biomarkers in the prediction of early cognitive impairment in AD and PD is significant for understanding the progress of neurodegenerative diseases. METHODS A multi-scale attention-based deep learning method is proposed to perform computer-aided diagnosis for neurodegenerative disease based on Hippocampal subfields. First, the two dimensional (2D) Hippocampal Mapping Image (HMI) is constructed and used as input of three branches of the following network. Second, the multi-scale module and attention module are integrated into the 2D residual network to improve the diversity of the extracted features and capture significance of various voxels for classification. Finally, the role of Hippocampal subfields in the progression of different neurodegenerative diseases is analyzed using the proposed method. RESULTS Classification experiments between normal control (NC), mild cognitive impairment (MCI), AD, PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) are carried out using the proposed method. Experimental results show that subfields subiculum, presubiculum, CA1, and molecular layer are strongly correlated with cognitive impairment in AD and MCI, subfields GC-DG and fimbria are sensitive in detecting early stage of cognitive impairment in MCI, subfields CA3, CA4, GC-DG, and CA1 show significant atrophy in PD. For exploring the role of Hippocampal subfields in PD cognitive impairment, we find that left parasubiculum, left HATA and left presubiculum could be important biomarkers for predicting conversion from PD-NC to PD-MCI. CONCLUSION The proposed multi-scale attention-based network can effectively discover the correlation between subfields and neurodegenerative diseases. Experimental results are consistent with previous clinical studies, which will be useful for further exploring the role of Hippocampal subfields in neurodegenerative disease progression.
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Affiliation(s)
- Hongbo Xu
- School of Computer Science and Technology, University of Chinese Academy of Sciences, Beijing, China
| | - Yan Liu
- School of Computer Science and Technology, University of Chinese Academy of Sciences, Beijing, China.
| | - Ling Wang
- School of Information and Communication Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiangzhu Zeng
- Department of Radiology, Peking University Third Hospital, Beijing, China.
| | - Yingying Xu
- Department of Radiology, Peking University Sixth Hospital, Beijing, China
| | - Zeng Wang
- Department of Radiology, Peking University Third Hospital, Beijing, China
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13
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Relations of hippocampal subfields atrophy patterns with memory and biochemical changes in end stage renal disease. Sci Rep 2023; 13:2982. [PMID: 36804419 PMCID: PMC9941083 DOI: 10.1038/s41598-023-29083-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/30/2023] [Indexed: 02/22/2023] Open
Abstract
End-stage renal disease (ESRD) results in hippocampal volume reduction, but the hippocampal subfields atrophy patterns cannot be identified. We explored the volumes and asymmetry of the hippocampal subfields and their relationships with memory function and biochemical changes. Hippocampal global and subfields volumes were derived from 33 ESRD patients and 46 healthy controls (HCs) from structural MRI. We compared the volume and asymmetric index of each subfield, with receiver operating characteristic curve analysis to evaluate the differentiation between ESRD and HCs. The relations of hippocampal subfield volumes with memory performance and biochemical data were investigated in ESRD group. ESRD patients had smaller hippocampal subfield volumes, mainly in the left CA1 body, left fimbria, right molecular layer head, right molecular layer body and right HATA. The right molecular layer body exhibited the highest accuracy for differentiating ESRD from HCs, with a sensitivity of 80.43% and specificity of 72.73%. Worse learning process (r = 0.414, p = 0.032), immediate recall (r = 0.396, p = 0.041) and delayed recall (r = 0.482, p = 0.011) was associated with left fimbria atrophy. The left fimbria volume was positively correlated with Hb (r = 0.388, p = 0.05); the left CA1 body volume was negatively correlated with Urea (r = - 0.469, p = 0.016). ESRD patients showed global and hippocampal subfields atrophy. Left fimbria atrophy was related to memory function. Anemia and Urea level may be associated with the atrophy of left fimbria and CA1 body, respectively.
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14
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Deng JH, Zhang HW, Liu XL, Deng HZ, Lin F. Morphological changes in Parkinson's disease based on magnetic resonance imaging: A mini-review of subcortical structures segmentation and shape analysis. World J Psychiatry 2022; 12:1356-1366. [PMID: 36579355 PMCID: PMC9791612 DOI: 10.5498/wjp.v12.i12.1356] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/02/2022] [Accepted: 11/22/2022] [Indexed: 12/16/2022] Open
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra, resulting in clinical symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. The pathophysiological changes in PD are inextricably linked to the subcortical structures. Shape analysis is a method for quantifying the volume or surface morphology of structures using magnetic resonance imaging. In this review, we discuss the recent advances in morphological analysis techniques for studying the subcortical structures in PD in vivo. This approach includes available pipelines for volume and shape analysis, focusing on the morphological features of volume and surface area.
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Affiliation(s)
- Jin-Huan Deng
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Han-Wen Zhang
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Xiao-Lei Liu
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Hua-Zhen Deng
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Fan Lin
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
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15
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Wu J, Shahid SS, Lin Q, Hone-Blanchet A, Smith JL, Risk BB, Bisht AS, Loring DW, Goldstein FC, Levey AI, Lah JJ, Qiu D. Multimodal magnetic resonance imaging reveals distinct sensitivity of hippocampal subfields in asymptomatic stage of Alzheimer’s disease. Front Aging Neurosci 2022; 14:901140. [PMID: 36034141 PMCID: PMC9413400 DOI: 10.3389/fnagi.2022.901140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 07/28/2022] [Indexed: 11/13/2022] Open
Abstract
While hippocampal atrophy and its regional susceptibility to Alzheimer’s disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: n = 40) and healthy older adults with negative (HO−: n = 47) and positive (HO+ : n = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-β, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes.
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Affiliation(s)
- Junjie Wu
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States
- *Correspondence: Junjie Wu, ,
| | - Syed S. Shahid
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Qixiang Lin
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
| | - Antoine Hone-Blanchet
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Jeremy L. Smith
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States
| | - Benjamin B. Risk
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA, United States
| | - Aditya S. Bisht
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
| | - David W. Loring
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
| | - Felicia C. Goldstein
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
| | - Allan I. Levey
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
| | - James J. Lah
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
- James J. Lah,
| | - Deqiang Qiu
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States
- Joint Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States
- Deqiang Qiu,
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16
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Chi CH, Yang FC, Chang YL. Age-related volumetric alterations in hippocampal subiculum region are associated with reduced retention of the “when” memory component. Brain Cogn 2022; 160:105877. [DOI: 10.1016/j.bandc.2022.105877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 04/18/2022] [Accepted: 04/22/2022] [Indexed: 11/02/2022]
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17
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Lopes MJP, Delmondes GDA, Leite GMDL, Cavalcante DRA, Aquino PÉAD, Lima FAVD, Neves KRT, Costa AS, Oliveira HDD, Bezerra Felipe CF, Pampolha Lima IS, Kerntopf MR, Viana GSDB. The Protein-Rich Fraction from Spirulina platensis Exerts Neuroprotection in Hemiparkinsonian Rats by Decreasing Brain Inflammatory-Related Enzymes and Glial Fibrillary Acidic Protein Expressions. J Med Food 2022; 25:695-709. [PMID: 35834631 DOI: 10.1089/jmf.2021.0100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
Spirulina platensis is a cyanobacterium with high protein content and presenting neuroprotective effects. Now, we studied a protein-enriched fraction (SPF), on behavior, neurochemical and immunohistochemical (IHC) assays in hemiparkinsonian rats, distributed into the groups: SO (sham-operated), 6-hydroxydopamine (6-OHDA), and 6-OHDA (treated with SPF, 5 and 10 mg/kg, p.o., 15 days). Afterward, animals were subjected to behavioral tests and euthanized, and brain areas used for neurochemical and IHC assays. SPF partly reversed the changes in the apomorphine-induced rotations, open field and forced swim tests, and also the decrease in striatal dopamine and 3,4-dihydroxyphenylacetic acid contents seen in hemiparkinsonian rats. Furthermore, SPF reduced brain oxidative stress and increased striatal expressions of tyrosine hydroxylase and dopamine transporter and significantly reduced hippocampal inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein expressions. The data suggest that the protein fraction from S. platensis, through its brain anti-inflammatory and antioxidative actions, exerts neuroprotective effects that could benefit patients affected by neurodegenerative diseases, like Parkinson's disease.
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Affiliation(s)
| | | | | | | | | | | | | | - Andréa Santos Costa
- Faculty of Medicine of the Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil
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Morphological basis of Parkinson disease-associated cognitive impairment: an update. J Neural Transm (Vienna) 2022; 129:977-999. [PMID: 35726096 DOI: 10.1007/s00702-022-02522-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/25/2022] [Indexed: 12/15/2022]
Abstract
Cognitive impairment is one of the most salient non-motor symptoms of Parkinson disease (PD) that poses a significant burden on the patients and carers as well as being a risk factor for early mortality. People with PD show a wide spectrum of cognitive dysfunctions ranging from subjective cognitive decline and mild cognitive impairment (MCI) to frank dementia. The mean frequency of PD with MCI (PD-MCI) is 25.8% and the pooled dementia frequency is 26.3% increasing up to 83% 20 years after diagnosis. A better understanding of the underlying pathological processes will aid in directing disease-specific treatment. Modern neuroimaging studies revealed considerable changes in gray and white matter in PD patients with cognitive impairment, cortical atrophy, hypometabolism, dopamine/cholinergic or other neurotransmitter dysfunction and increased amyloid burden, but multiple mechanism are likely involved. Combined analysis of imaging and fluid markers is the most promising method for identifying PD-MCI and Parkinson disease dementia (PDD). Morphological substrates are a combination of Lewy- and Alzheimer-associated and other concomitant pathologies with aggregation of α-synuclein, amyloid, tau and other pathological proteins in cortical and subcortical regions causing destruction of essential neuronal networks. Significant pathological heterogeneity within PD-MCI reflects deficits in various cognitive domains. This review highlights the essential neuroimaging data and neuropathological changes in PD with cognitive impairment, the amount and topographical distribution of pathological protein aggregates and their pathophysiological relevance. Large-scale clinicopathological correlative studies are warranted to further elucidate the exact neuropathological correlates of cognitive impairment in PD and related synucleinopathies as a basis for early diagnosis and future disease-modifying therapies.
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Coad BM, Ghomroudi PA, Sims R, Aggleton JP, Vann SD, Metzler-Baddeley C. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. Neurobiol Aging 2022; 113:39-54. [PMID: 35303671 PMCID: PMC9084919 DOI: 10.1016/j.neurobiolaging.2022.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/18/2022] [Accepted: 02/12/2022] [Indexed: 12/02/2022]
Abstract
Age-related inverted U-shaped curve of hippocampal myelin/neurite packing. Reduced hippocampal myelin/neurite packing and size/complexity in obesity. APOE modifies the effects of obesity on hippocampal size/complexity. Age-related slowing of spatial navigation but no risk effects on cognition. CA/DG predict episodic memory and subiculum predicts spatial navigation performance. Characterizing age- and risk-related hippocampal vulnerabilities may inform about the neural underpinnings of cognitive decline. We studied the impact of three risk-factors, Apolipoprotein (APOE)-ε4, a family history of dementia, and central obesity, on the CA1, CA2/3, dentate gyrus and subiculum of 158 cognitively healthy adults (38-71 years). Subfields were labelled with the Automatic Segmentation of Hippocampal Subfields and FreeSurfer (version 6) protocols. Volumetric and microstructural measurements from quantitative magnetization transfer and Neurite Orientation Density and Dispersion Imaging were extracted for each subfield and reduced to three principal components capturing apparent myelin/neurite packing, size/complexity, and metabolism. Aging was associated with an inverse U-shaped curve on myelin/neurite packing and affected all subfields. Obesity led to reductions in myelin/neurite packing and size/complexity regardless of APOE and family history of dementia status. However, amongst individuals with a healthy Waist-Hip-Ratio, APOE ε4 carriers showed lower size/complexity than non-carriers. Segmentation protocol type did not affect this risk pattern. These findings reveal interactive effects between APOE and central obesity on the hippocampal formation of cognitively healthy adults.
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20
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Hou Y, Shang H. Magnetic Resonance Imaging Markers for Cognitive Impairment in Parkinson’s Disease: Current View. Front Aging Neurosci 2022; 14:788846. [PMID: 35145396 PMCID: PMC8821910 DOI: 10.3389/fnagi.2022.788846] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 01/03/2022] [Indexed: 12/24/2022] Open
Abstract
Cognitive impairment (CI) ranging from mild cognitive impairment (MCI) to dementia is a common and disturbing complication in patients with Parkinson’s disease (PD). Numerous studies have focused on neuropathological mechanisms underlying CI in PD, along with the identification of specific biomarkers for CI. Magnetic resonance imaging (MRI), a promising method, has been adopted to examine the changes in the brain and identify the candidate biomarkers associated with CI. In this review, we have summarized the potential biomarkers for CI in PD which have been identified through multi-modal MRI studies. Structural MRI technology is widely used in biomarker research. Specific patterns of gray matter atrophy are promising predictors of the evolution of CI in patients with PD. Moreover, other MRI techniques, such as MRI related to small-vessel disease, neuromelanin-sensitive MRI, quantitative susceptibility mapping, MR diffusion imaging, MRI related to cerebrovascular abnormality, resting-state functional MRI, and proton magnetic resonance spectroscopy, can provide imaging features with a good degree of prediction for CI. In the future, novel combined biomarkers should be developed using the recognized analysis tools and predictive algorithms in both cross-sectional and longitudinal studies.
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21
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Khlif MS, Werden E, Bird LJ, Egorova-Brumley N, Brodtmann A. Atrophy of Ipsilesional Hippocampal Subfields Vary Over First Year After Ischemic Stroke. J Magn Reson Imaging 2021; 56:273-281. [PMID: 34837426 DOI: 10.1002/jmri.28009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND The structural integrity of hippocampal subfields has been investigated in many neurological disorders and was shown to be better associated with cognitive performance than whole hippocampus. In stroke, hippocampal atrophy is linked to cognitive impairment, but it is unknown whether the hippocampal subfields atrophy differently. PURPOSE To evaluate longitudinal hippocampal subfield atrophy in first year poststroke, in comparison with atrophy in healthy individuals. STUDY TYPE Cohort. SUBJECTS A total of 92 ischemic stroke (age: 67 ± 12 years, 63 men) and 39 healthy participants (age: 69 ± 7 years, 24 men). FIELD STRENGTH/SEQUENCE A3 T/T1-MPRAGE, T2-SPACE, and T2-FLAIR. ASSESSMENT FreeSurfer (6.0) was used to delineate 12 hippocampal subfields. Whole hippocampal volume was computed as sum of subfield volumes excluding hippocampal fissure volume. Separate assessments were completed for contralesional and ipsilesional hippocampi. STATISTICAL TESTS A mixed-effect regression model was used to compare subfield volumes cross-sectionally between healthy and stroke groups and longitudinally between 3-month and 12-month timepoints. False discovery rate at 0.05 significance level was used to correct for multiple comparisons. Also, a receiver operating characteristic (ROC) curve analysis was performed to assess differentiation between healthy and stroke participants based on subfield volumes. RESULTS There were no volume differences between groups at 3 months, but there was a significant difference (P = 0.027) in whole hippocampal volume reduction over time between control and stroke ipsilesionally. Thus, the ipsilesional whole hippocampal volume in stroke became significantly smaller (P = 0.035) at 12 months. The hippocampal tail was the highest single-region contributor (22.7%) to ipsilesional hippocampal atrophy (1.19%) over 9 months. The cornu ammonis areas (CA1) subfield volume reduction was minimal in controls and stroke contralesionally but significant ipsilesionally (P = 0.007). CA1 volume significantly outperformed whole hippocampal volume (P < 0.01) in discriminating between stroke participants and healthy controls in ROC curve analysis. DATA CONCLUSION Greater stroke-induced effects were observed in the ipsilesional hippocampus anteriorly in CA1 and posteriorly in the hippocampal tail. Atrophy of CA1 and hippocampal tail may provide a better link to cognitive impairment than whole hippocampal atrophy. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 3.
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Affiliation(s)
- Mohamed Salah Khlif
- The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
| | - Emilio Werden
- The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
| | - Laura J Bird
- The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
| | - Natalia Egorova-Brumley
- The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.,Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
| | - Amy Brodtmann
- The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.,Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.,Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia.,Eastern Cognitive Disorders Clinic, Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
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22
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Cremona S, Zago L, Mellet E, Petit L, Laurent A, Pepe A, Tsuchida A, Beguedou N, Joliot M, Tzourio C, Mazoyer B, Crivello F. Novel characterization of the relationship between verbal list-learning outcomes and hippocampal subfields in healthy adults. Hum Brain Mapp 2021; 42:5264-5277. [PMID: 34453474 PMCID: PMC8519870 DOI: 10.1002/hbm.25614] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/29/2021] [Accepted: 07/20/2021] [Indexed: 11/10/2022] Open
Abstract
The relationship between hippocampal subfield volumetry and verbal list‐learning test outcomes have mostly been studied in clinical and elderly populations, and remain controversial. For the first time, we characterized a relationship between verbal list‐learning test outcomes and hippocampal subfield volumetry on two large separate datasets of 447 and 1,442 healthy young and middle‐aged adults, and explored the processes that could explain this relationship. We observed a replicable positive linear correlation between verbal list‐learning test free recall scores and CA1 volume, specific to verbal list learning as demonstrated by the hippocampal subfield volumetry independence from verbal intelligence. Learning meaningless items was also positively correlated with CA1 volume, pointing to the role of the test design rather than word meaning. Accordingly, we found that association‐based mnemonics mediated the relationship between verbal list‐learning test outcomes and CA1 volume. This mediation suggests that integrating items into associative representations during verbal list‐learning tests explains CA1 volume variations: this new explanation is consistent with the associative functions of the human CA1.
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Affiliation(s)
- Sandrine Cremona
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Laure Zago
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Emmanuel Mellet
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Laurent Petit
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Alexandre Laurent
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Antonietta Pepe
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Ami Tsuchida
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Naka Beguedou
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Marc Joliot
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
| | - Christophe Tzourio
- Université de Bordeaux - Département Santé publique, INSERM, BPH U 1219, Bordeaux, France
| | - Bernard Mazoyer
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France.,Institut des maladies neurodégénératives clinique, CHU de Bordeaux, Bordeaux, France
| | - Fabrice Crivello
- Université de Bordeaux - Neurocampus, CEA, CNRS, IMN UMR 5293, Bordeaux, France
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23
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Loenneker HD, Artemenko C, Willmes K, Liepelt-Scarfone I, Nuerk HC. Deficits in or preservation of basic number processing in Parkinson's disease? A registered report. J Neurosci Res 2021; 99:2390-2405. [PMID: 34184307 DOI: 10.1002/jnr.24907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 03/02/2021] [Accepted: 03/12/2021] [Indexed: 11/10/2022]
Abstract
Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health-care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.
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Affiliation(s)
| | - Christina Artemenko
- Department of Psychology, University of Tuebingen, Tuebingen, Germany.,LEAD Graduate School & Research Network, University of Tuebingen, Tuebingen, Germany
| | - Klaus Willmes
- Department of Neurology, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Inga Liepelt-Scarfone
- Department of Clinical Neurodegeneration, Hertie Institute for Clinical Brain Research, Tuebingen, Germany.,German Centre for Neurodegenerative Diseases, Tuebingen, Germany.,IB-Hochschule für Gesundheit und Soziales, Stuttgart, Germany
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24
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Khlif MS, Bird LJ, Restrepo C, Khan W, Werden E, Egorova‐Brumley N, Brodtmann A. Hippocampal subfield volumes are associated with verbal memory after first-ever ischemic stroke. ALZHEIMER'S & DEMENTIA (AMSTERDAM, NETHERLANDS) 2021; 13:e12195. [PMID: 34136634 PMCID: PMC8197170 DOI: 10.1002/dad2.12195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/13/2021] [Accepted: 04/15/2021] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Hippocampal subfield volumes are more closely associated with cognitive impairment than whole hippocampal volume in many diseases. Both memory and whole hippocampal volume decline after stroke. Understanding the subfields' temporal evolution could reveal valuable information about post-stroke memory. METHODS We sampled 120 participants (38 control, 82 stroke), with cognitive testing and 3T-MRI available at 3 months and 3 years, from the Cognition and Neocortical Volume after Stroke (CANVAS) study. Verbal memory was assessed using the Hopkins Verbal Learning Test-Revised. Subfields were delineated using FreeSurfer. We used partial Pearson's correlation to assess the associations between subfield volumes and verbal memory scores, adjusting for years of education, sex, and stroke side. RESULTS The left cornu ammonis areas 2/3 and hippocampal tail volumes were significantly associated with verbal memory 3-month post-stroke. At 3 years, the associations became stronger and involved more subfields. DISCUSSION Hippocampal subfield volumes may be a useful biomarker for post-stroke cognitive impairment.
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Affiliation(s)
- Mohamed Salah Khlif
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Laura J. Bird
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Carolina Restrepo
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Wasim Khan
- Department of NeuroscienceCentral Clinical SchoolMonash UniversityClaytonVictoriaAustralia
- Department of Neuroimaging Institute of PsychiatryPsychology, and Neuroscience (IoPPN), King's College LondonLondonUK
| | - Emilio Werden
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Natalia Egorova‐Brumley
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
- Melbourne School of Psychological SciencesUniversity of MelbourneParkvilleVictoriaAustralia
| | - Amy Brodtmann
- The Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleVictoriaAustralia
- Department of NeurologyAustin HealthHeidelbergVictoriaAustralia
- Eastern Cognitive Disorders ClinicBox Hill HospitalMonash UniversityBox HillVictoriaAustralia
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25
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Pourzinal D, Yang JHJ, Bakker A, McMahon KL, Byrne GJ, Pontone GM, Mari Z, Dissanayaka NN. Hippocampal correlates of episodic memory in Parkinson's disease: A systematic review of magnetic resonance imaging studies. J Neurosci Res 2021; 99:2097-2116. [PMID: 34075634 DOI: 10.1002/jnr.24863] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 12/15/2022]
Abstract
The present review asks whether magnetic resonance imaging (MRI) studies are able to define neural correlates of episodic memory within the hippocampus in Parkinson's disease (PD). Systematic searches were performed in PubMed, Web of Science, Medline, CINAHL, and EMBASE using search terms related to structural and functional MRI (fMRI), the hippocampus, episodic memory, and PD. Risk of bias was assessed for each study using the Newtown-Ottawa Scale. Thirty-nine studies met inclusion criteria; eight fMRI, seven diffusion MRI (dMRI), and 24 structural MRI (14 exploring whole hippocampus and 10 exploring hippocampal subfields). Critical analysis of the literature revealed mixed evidence from functional and dMRI, but stronger evidence from sMRI of the hippocampus as a biomarker for episodic memory impairment in PD. Hippocampal subfield studies most often implicated CA1, CA3/4, and subiculum volume in episodic memory and cognitive decline in PD. Despite differences in imaging methodology, study design, and sample characteristics, MRI studies have helped elucidate an important neural correlate of episodic memory impairment in PD with both clinical and theoretical implications. Natural progression of this work encourages future research on hippocampal subfield function as a potential biomarker of, or therapeutic target for, episodic memory dysfunction in PD.
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Affiliation(s)
- Dana Pourzinal
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia
| | - Ji Hyun J Yang
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia
| | - Arnold Bakker
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.,Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| | - Katie L McMahon
- School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
| | - Gerard J Byrne
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.,Mental Health Service, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia
| | - Gregory M Pontone
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.,Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| | - Zoltan Mari
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
| | - Nadeeka N Dissanayaka
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.,Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.,School of Psychology, The University of Queensland, Brisbane, QLD, Australia
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26
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Shen S, Wang X, Lv H, Shi Y, Xiao L. PADI4 mediates autophagy and participates in the role of ganoderic acid A monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway. Biosci Biotechnol Biochem 2021; 85:1818-1829. [PMID: 33963744 DOI: 10.1093/bbb/zbab054] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/04/2021] [Indexed: 12/15/2022]
Abstract
The effects of PADI4 and GAA on the senescence of Alzheimer's cells were explored in the present work. HT22 cells were treated with Aβ25-35 to establish an Alzheimer's model and were then treated with different concentrations of GAA and transfected with a siPADI4 lentiviral vector. GAA could reverse the effects of Aβ25-35 on inhibiting cell viability and promoting apoptosis and senescence. siPADI4 reduced Aβ25-35-induced cell viability and upregulated Aβ25-35-induced cell apoptosis and senescence, as well as partially reversed the effect of GAA on cells, and these results were confirmed by detecting the expressions of senescence- and apoptosis-related proteins. In addition, siPADI4 was found to promote the phosphorylation of Akt and mTOR, which was partially reversed by GAA. In conclusion, PADI4 mediates autophagy and participates in the role of GAA monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway.
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Affiliation(s)
- Shuhua Shen
- Disease Prevention and Health Management Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.,Disease Prevention and Health Management Center, People's Hospital of Songyang, Lishui, Zhejiang Province, China
| | - Xiaoming Wang
- Disease Prevention and Health Management Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Hang Lv
- Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yuan Shi
- Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Luwei Xiao
- Disease Prevention and Health Management Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
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27
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Inguanzo A, Sala-Llonch R, Segura B, Erostarbe H, Abos A, Campabadal A, Uribe C, Baggio H, Compta Y, Marti M, Valldeoriola F, Bargallo N, Junque C. Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson’s disease. Parkinsonism Relat Disord 2021; 82:16-23. [DOI: 10.1016/j.parkreldis.2020.11.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 09/15/2020] [Accepted: 11/10/2020] [Indexed: 11/24/2022]
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28
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Sämann PG, Iglesias JE, Gutman B, Grotegerd D, Leenings R, Flint C, Dannlowski U, Clarke‐Rubright EK, Morey RA, Erp TG, Whelan CD, Han LKM, Velzen LS, Cao B, Augustinack JC, Thompson PM, Jahanshad N, Schmaal L. FreeSurfer
‐based segmentation of hippocampal subfields: A review of methods and applications, with a novel quality control procedure for
ENIGMA
studies and other collaborative efforts. Hum Brain Mapp 2020; 43:207-233. [PMID: 33368865 PMCID: PMC8805696 DOI: 10.1002/hbm.25326] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/26/2020] [Accepted: 12/13/2020] [Indexed: 12/11/2022] Open
Abstract
Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi‐)genetics. Finally, we highlight points where FreeSurfer‐based hippocampal subfield studies may be optimized.
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Affiliation(s)
| | - Juan Eugenio Iglesias
- Centre for Medical Image Computing University College London London UK
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital/Harvard Medical School Boston Massachusetts US
- Computer Science and AI Laboratory (CSAIL), Massachusetts Institute of Technology (MIT) Cambridge Massachusetts US
| | - Boris Gutman
- Department of Biomedical Engineering Illinois Institute of Technology Chicago USA
| | | | - Ramona Leenings
- Department of Psychiatry University of Münster Münster Germany
| | - Claas Flint
- Department of Psychiatry University of Münster Münster Germany
- Department of Mathematics and Computer Science University of Münster Germany
| | - Udo Dannlowski
- Department of Psychiatry University of Münster Münster Germany
| | - Emily K. Clarke‐Rubright
- Brain Imaging and Analysis Center, Duke University Durham North Carolina USA
- VISN 6 MIRECC, Durham VA Durham North Carolina USA
| | - Rajendra A. Morey
- Brain Imaging and Analysis Center, Duke University Durham North Carolina USA
- VISN 6 MIRECC, Durham VA Durham North Carolina USA
| | - Theo G.M. Erp
- Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior University of California Irvine California USA
- Center for the Neurobiology of Learning and Memory University of California Irvine Irvine California USA
| | - Christopher D. Whelan
- Imaging Genetics Center Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California Los Angeles California USA
| | - Laura K. M. Han
- Department of Psychiatry Amsterdam University Medical Centers, Vrije Universiteit and GGZ inGeest, Amsterdam Neuroscience Amsterdam The Netherlands
| | - Laura S. Velzen
- Orygen Parkville Australia
- Centre for Youth Mental Health The University of Melbourne Melbourne Australia
| | - Bo Cao
- Department of Psychiatry, Faculty of Medicine & Dentistry University of Alberta Edmonton Canada
| | - Jean C. Augustinack
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital/Harvard Medical School Boston Massachusetts US
| | - Paul M. Thompson
- Imaging Genetics Center Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California Los Angeles California USA
| | - Neda Jahanshad
- Imaging Genetics Center Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California Los Angeles California USA
| | - Lianne Schmaal
- Orygen Parkville Australia
- Centre for Youth Mental Health The University of Melbourne Melbourne Australia
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29
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Sarasso E, Agosta F, Piramide N, Filippi M. Progression of grey and white matter brain damage in Parkinson's disease: a critical review of structural MRI literature. J Neurol 2020; 268:3144-3179. [PMID: 32378035 DOI: 10.1007/s00415-020-09863-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 04/23/2020] [Indexed: 10/24/2022]
Abstract
The current review summarizes the current knowledge on longitudinal cortical and subcortical grey and white matter MRI findings assessed using T1-weighted and one-tensor diffusion-weighted MRI in Parkinson's disease (PD) patients. Results were reviewed according to disease duration, disease severity and cognitive impairment. The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage. Analyzing results according to the patient cognitive status, only a few studies used longitudinal MRI metrics to predict mild cognitive impairment or dementia conversion in PD patients, suggesting that atrophy of the hippocampus, fronto-temporal areas, caudate, thalamus and accumbens might play a role in this process. Stratifying patients according to disease severity, findings appear partially controversial, although showing a progressive atrophy of basal ganglia over 1 year of follow up and a widespread cortical thinning over 3-6 years in mild to moderate PD patients. Finally, microstructural damage of the main motor and associative WM tracts seems to be present, and rapidly progress, even in the early phase of PD. The utility of structural MRI metrics as biomarkers of PD progression and their role in improving the accuracy of disease progression prediction is still debated.
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Affiliation(s)
- Elisabetta Sarasso
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy.,Laboratory of Movement Analysis, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Agosta
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Noemi Piramide
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. .,Vita-Salute San Raffaele University, Milan, Italy. .,Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. .,Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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30
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Krajcovicova L, Klobusiakova P, Rektorova I. Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition. Curr Neurol Neurosci Rep 2019; 19:85. [PMID: 31720859 PMCID: PMC6854046 DOI: 10.1007/s11910-019-1006-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. RECENT FINDINGS The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion.
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Affiliation(s)
- Lenka Krajcovicova
- Applied Neuroscience Research Group, CEITEC, Masaryk University, Kamenice 5, Brno, Czech Republic
- First Department of Neurology, Faculty of Medicine, St. Anne's University Hospital, Masaryk University, Pekarska 53, Brno, Czech Republic
| | - Patricia Klobusiakova
- Applied Neuroscience Research Group, CEITEC, Masaryk University, Kamenice 5, Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Irena Rektorova
- Applied Neuroscience Research Group, CEITEC, Masaryk University, Kamenice 5, Brno, Czech Republic.
- First Department of Neurology, Faculty of Medicine, St. Anne's University Hospital, Masaryk University, Pekarska 53, Brno, Czech Republic.
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