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Li J, An Y, Qin J, Mohamad NS, Ramli I. Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus. Front Med (Lausanne) 2025; 12:1530462. [PMID: 40417692 PMCID: PMC12098386 DOI: 10.3389/fmed.2025.1530462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 04/18/2025] [Indexed: 05/27/2025] Open
Abstract
Introduction Type 2 diabetes mellitus (T2DM) is often accompanied by bone metabolic disorders and cognitive impairment, forming an interactive network through metabolic derangements, oxidative stress, and inflammatory responses. Hyperglycemia and insulin resistance disrupt bone remodeling leading to osteoporosis while simultaneously impairing cognition via blood-brain barrier damage and neuroinflammation. Osteogenic factors like osteocalcin may bidirectionally regulate glucose metabolism and brain function, suggesting that "bone-brain axis" dysregulation could be a potential mechanism underlying cognitive impairment in T2DM. This study aims to characterize cognitive function patterns in T2DM patients with bone metabolic abnormalities and their clinical correlations, providing a basis for multisystemic interventions. Methods The general clinical data, osteocalcin (OC), glycosylated hemoglobin (HbA1c), bone mineral density (BMD), and the Montreal Cognitive Assessment (MoCA) scores of 50 patients with T2DM were collected. According to whether cognitive impairment occurred or not, one-way ANOVA was performed to analyze the correlation between cognitive and clinical indicators, BMD and OC. Multiple linear regression analysis was performed with cognition and bone density as dependent variables and other factors as independent variables. Results T2DM subjects were grouped according to bone mass. The osteoporosis group had the lowest MoCA score and bone density, followed by the osteopenia group. There were 16 cases (16/17 94.12%) of cognitive impairment in the osteoporosis group, 13 cases (13/17 76.47%) of cognitive impairment in the osteopenia group, and 3 cases (3/16 18.75%) of cognitive impairment in the normal bone mass group. Compared with the normal cognitive group, the MoCA score, OC measurement and BMD of the patients in the cognitive impairment group were lower (P < 0.05). BMD (r = 0.686, P = 0.000), OC (r = 0.756, P = 0.000) are positively correlated with MoCA score. OC (r = 0.690, P = 0.000) and Age (r = -0.032, P = 0.045) are positively correlated with BMD. Multivariate linear regression analysis found that with cognition as the dependent variable, the decrease in BMD (P = 0.028) and OC (P = 0.000) aggravated the occurrence of cognitive impairment; with BMD as the dependent variable, the decline in cognition (P = 0.028) and OC (P = 0.029) aggravated the decrease in BMD. Conclusion T2DM, osteoporosis, and cognitive impairment form pathological connections through metabolic disorders, chronic inflammation, and bidirectional regulatory networks of the "bone-brain axis," with osteocalcin serving as a key mediator that maintains bone remodeling balance while also exerting cross-domain regulation over central insulin signaling and synaptic plasticity. Understanding these interactive mechanisms provides a basis for developing combined screening models integrating bone density and cognitive assessments, and promotes multidisciplinary collaborative interventions across endocrinology, orthopedics, and neurology to improve overall outcomes for T2DM patients.
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Affiliation(s)
- Jiang Li
- Faculty of Health Sciences, Universiti Teknologi MARA, Shah Alam, Malaysia
- The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yuxiao An
- The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Jian Qin
- Faculty of Health Sciences, Universiti Teknologi MARA, Shah Alam, Malaysia
- The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | | | - Izzad Ramli
- College of Computing, Informatics and Mathematics, Universiti Teknologi MARA, Shah Alam, Malaysia
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Pu Z, Huang H, Li M, Li H, Shen X, Du L, Wu Q, Fang X, Meng X, Ni Q, Li G, Cui D. Screening tools for subjective cognitive decline and mild cognitive impairment based on task-state prefrontal functional connectivity: a functional near-infrared spectroscopy study. Neuroimage 2025; 310:121130. [PMID: 40058532 DOI: 10.1016/j.neuroimage.2025.121130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) carry the risk of progression to dementia, and accurate screening methods for these conditions are urgently needed. Studies have suggested the potential ability of functional near-infrared spectroscopy (fNIRS) to identify MCI and SCD. The present fNIRS study aimed to develop an early screening method for SCD and MCI based on activated prefrontal functional connectivity (FC) during the performance of cognitive scales and subject-wise cross-validation via machine learning. METHODS Activated prefrontal FC data measured by fNIRS were collected from 55 normal controls, 80 SCD patients, and 111 MCI patients. Differences in FC were analyzed among the groups, and FC strength and cognitive scale performance were extracted as features to build classification and predictive models through machine learning. Model performance was assessed based on accuracy, specificity, sensitivity, and area under the curve (AUC) with 95 % confidence interval (CI) values. RESULTS Statistical analysis revealed a trend toward more impaired prefrontal FC with declining cognitive function. Prediction models were built by combining features of prefrontal FC and cognitive scale performance and applying machine learning models, The models showed generally satisfactory abilities to differentiate among the three groups, especially those employing linear discriminant analysis, logistic regression, and support vector machine. Accuracies of 92.0 % for MCI vs. NC, 80.0 % for MCI vs. SCD, and 76.1 % for SCD vs. NC were achieved, and the highest AUC values were 97.0 % (95 % CI: 94.6 %-99.3 %) for MCI vs. NC, 87.0 % (95 % CI: 81.5 %-92.5 %) for MCI vs. SCD, and 79.2 % (95 % CI: 71.0 %-87.3 %) for SCD vs. NC. CONCLUSION The developed screening method based on fNIRS and machine learning has the potential to predict early-stage cognitive impairment based on prefrontal FC data collected during cognitive scale-induced activation.
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Affiliation(s)
- Zhengping Pu
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, PR China; Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Hongna Huang
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, PR China
| | - Man Li
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Hongyan Li
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Xiaoyan Shen
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Lizhao Du
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, PR China
| | - Qingfeng Wu
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Xiaomei Fang
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Xiang Meng
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Qin Ni
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China
| | - Guorong Li
- Department of Psychogeriatrics, Kangci Hospital of Jiaxissng, Tongxiang 314500, Zhejiang, PR China.
| | - Donghong Cui
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, PR China.
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Wang XL, Zhao YR, Yu Y, Mao ZF, Tan SX, Yu SS. Impact of dietary nutrition regimens based on body composition analysis on bone metabolism in Alzheimer's disease patients. World J Psychiatry 2025; 15:99008. [PMID: 39974500 PMCID: PMC11758049 DOI: 10.5498/wjp.v15.i2.99008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/27/2024] [Accepted: 12/17/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Body composition analysis (BCA) is primarily used in the management of conditions such as obesity and endocrine disorders. However, its potential in providing nutritional guidance for patients with Alzheimer's disease (AD) remains relatively unexplored. AIM To explore the clinical efficacy of BCA-based dietary nutrition scheme on bone metabolism in AD patients. METHODS This retrospective study included 96 patients with AD complicated by osteoporosis who were admitted to The Third Hospital of Quzhou between January 2023 and December 2024. Based on data from previous similar studies, the patients were randomly assigned to either a routine diet (RD) group (n = 48) or a personalized nutrition (PN) group (n = 48). The RD group received conventional dietary guidance, while the PN group received individualized diet intervention measures based on human BCA. The intervention period lasted for 12 weeks. Bone mineral density (BMD), body mass index (BMI), muscle mass, mineral content, osteocalcin, 25-hydroxyvitamin D, procollagen type I N-terminal propeptide (PINP), beta C-terminal telopeptide of type I collagen (β-CTX), and serum calcium were measured and compared between the two groups before and 12 weeks after the intervention. RESULTS No significant differences were observed between groups in terms of age, sex, height, BMI, or other baseline data (P > 0.05). In both groups, BMI did not show significant changes after the intervention (P > 0.05), whereas muscle mass and mineral content were significantly increased (P < 0.05). After the intervention, BMI in the PN group did not differ significantly from that of the RD group, but muscle mass and mineral content were significantly higher in the PN group (P < 0.05). After the intervention, a higher proportion of patients in the PN group had a T score > -1 compared to the RD group (P < 0.05). The mini-mental state examination (MMSE) score was similar in both groups before the intervention. However, 12 weeks after the intervention, the MMSE score in the PN group was significantly higher than that in the RD group (P < 0.05). In both groups, the MMSE score significantly increased 12 weeks post-intervention compared to pre-intervention levels (P < 0.05). Before the intervention, the levels of osteocalcin, serum calcium, PINP, β-CTX, and 25-hydroxyvitamin D were not significantly different between the two groups (P > 0.05). After 12 weeks of intervention, the PN group exhibited higher levels of osteocalcin, serum calcium, and 25-hydroxyvitamin D, as well as lower levels of PINP and β-CTX, compared to the RD group (P < 0.05). In both groups, osteocalcin, serum calcium, and 25-hydroxyvitamin D levels were significantly higher, while PINP and β-CTX levels were significantly lower after 12 weeks of intervention compared to baseline (P < 0.05). CONCLUSION The human BCA-based dietary nutrition regimen plays a crucial role in improving BMD and bone metabolism, with effects that surpass those of conventional nutrition strategies. The findings of this study provide strong evidence for the nutritional management of AD patients.
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Affiliation(s)
- Xue-Lian Wang
- Department of Clinical Nutrition, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Yi-Ran Zhao
- Department of Rehabilitation Treatment Group, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Ying Yu
- Department of Geriatrics, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Zhi-Fang Mao
- Department of Rehabilitation Medicine, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Su-Xian Tan
- Department of Psychiatry, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Shan-Shan Yu
- Department of Geriatric Psychiatry, The Third Hospital of Quzhou, Quzhou 324000, Zhejiang Province, China
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Pu Z, Huang H, Li M, Li H, Shen X, Wu Q, Ni Q, Lin Y, Cui D. An exploration of distinguishing subjective cognitive decline and mild cognitive impairment based on resting-state prefrontal functional connectivity assessed by functional near-infrared spectroscopy. Front Aging Neurosci 2025; 16:1468246. [PMID: 39845444 PMCID: PMC11750998 DOI: 10.3389/fnagi.2024.1468246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 12/19/2024] [Indexed: 01/24/2025] Open
Abstract
Purpose Functional near-infrared spectroscopy (fNIRS) has shown feasibility in evaluating cognitive function and brain functional connectivity (FC). Therefore, this fNIRS study aimed to develop a screening method for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) based on resting-state prefrontal FC and neuropsychological tests via machine learning. Methods Functional connectivity data measured by fNIRS were collected from 55 normal controls (NCs), 80 SCD individuals, and 111 MCI individuals. Differences in FC were analyzed among the groups. FC strength and neuropsychological test scores were extracted as features to build classification and predictive models through machine learning. Model performance was assessed based on accuracy, specificity, sensitivity, and area under the curve (AUC) with 95% confidence interval (CI) values. Results Statistical analysis revealed a trend toward compensatory enhanced prefrontal FC in SCD and MCI individuals. The models showed a satisfactory ability to differentiate among the three groups, especially those employing linear discriminant analysis, logistic regression, and support vector machine. Accuracies of 94.9% for MCI vs. NC, 79.4% for MCI vs. SCD, and 77.0% for SCD vs. NC were achieved, and the highest AUC values were 97.5% (95% CI: 95.0%-100.0%) for MCI vs. NC, 83.7% (95% CI: 77.5%-89.8%) for MCI vs. SCD, and 80.6% (95% CI: 72.7%-88.4%) for SCD vs. NC. Conclusion The developed screening method based on resting-state prefrontal FC measured by fNIRS and machine learning may help predict early-stage cognitive impairment.
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Affiliation(s)
- Zhengping Pu
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Hongna Huang
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Man Li
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Hongyan Li
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Xiaoyan Shen
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Qingfeng Wu
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Qin Ni
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Yong Lin
- Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China
| | - Donghong Cui
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Qi X, He X, Peng Y, He X, Yang Q, Jiao K, Liu H. Roles of osteocalcin in the central nervous system. CNS Neurosci Ther 2024; 30:e70016. [PMID: 39252492 PMCID: PMC11386255 DOI: 10.1111/cns.70016] [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: 06/27/2024] [Revised: 08/04/2024] [Accepted: 08/13/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Bone-derived protein osteocalcin, which has beneficial effects on brain function, may be a future research direction for neurological disorders. A growing body of evidence suggests a link between osteocalcin and neurological disorders, but the exact relationship is contradictory and unclear. SCOPE OF REVIEW The aim of this review is to summarize the current research on the interaction between osteocalcin and the central nervous system and to propose some speculative future research directions. MAJOR CONCLUSIONS In the normal central nervous system, osteocalcin is involved in neuronal structure, neuroprotection, and the regulation of cognition and anxiety. Studies on osteocalcin-related abnormalities in the central nervous system are divided into animal model studies and human studies, depending on the subject. In humans, the link between osteocalcin and brain function is inconsistent. These conflicting data may be due to methodological inconsistencies. By reviewing the related literature on osteocalcin, some comorbidities of the bone and nervous system and future research directions related to osteocalcin are proposed.
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Affiliation(s)
- Xiao‐Shan Qi
- Department of RadiologyAffiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education lnstitutions, Medical Imaging Center of Guizhou ProvinceZunyiChina
- The First Clinical Medical CollegeZunyi Medical UniversityZunyiChina
| | - Xin He
- Department of RadiologyAffiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education lnstitutions, Medical Imaging Center of Guizhou ProvinceZunyiChina
| | - Ying Peng
- Department of RadiologyAffiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education lnstitutions, Medical Imaging Center of Guizhou ProvinceZunyiChina
| | - Xing‐Hong He
- Department of RadiologyAffiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education lnstitutions, Medical Imaging Center of Guizhou ProvinceZunyiChina
| | - Qian‐Yu Yang
- The First Clinical Medical CollegeZunyi Medical UniversityZunyiChina
| | - Kai Jiao
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, School of StomatologyThe Fourth Military Medical UniversityXi‘anChina
| | - Heng Liu
- Department of RadiologyAffiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education lnstitutions, Medical Imaging Center of Guizhou ProvinceZunyiChina
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Wanionok NE, Morel GR, Fernández JM. Osteoporosis and Alzheimer´s disease (or Alzheimer´s disease and Osteoporosis). Ageing Res Rev 2024; 99:102408. [PMID: 38969142 DOI: 10.1016/j.arr.2024.102408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 07/02/2024] [Accepted: 07/02/2024] [Indexed: 07/07/2024]
Abstract
Alzheimer's disease (AD) and osteoporosis are two diseases that mainly affect elderly people, with increases in the occurrence of cases due to a longer life expectancy. Several epidemiological studies have shown a reciprocal association between both diseases, finding an increase in incidence of osteoporosis in patients with AD, and a higher burden of AD in osteoporotic patients. This epidemiological relationship has motivated the search for molecules, genes, signaling pathways and mechanisms that are related to both pathologies. The mechanisms found in these studies can serve to improve treatments and establish better patient care protocols.
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Affiliation(s)
- Nahuel E Wanionok
- Laboratorio de Osteopatías y Metabolismo Mineral (LIOMM), Facultad de Cs. Exactas. Universidad Nacional de La Plata UNLP-CIC, Argentina
| | - Gustavo R Morel
- Biochemistry Research Institute of La Plata "Professor Doctor Rodolfo R. Brenner" (INIBIOLP), Argentina
| | - Juan M Fernández
- Laboratorio de Osteopatías y Metabolismo Mineral (LIOMM), Facultad de Cs. Exactas. Universidad Nacional de La Plata UNLP-CIC, Argentina.
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Zhang F, Zhang W. Research progress in Alzheimer's disease and bone-brain axis. Ageing Res Rev 2024; 98:102341. [PMID: 38759893 DOI: 10.1016/j.arr.2024.102341] [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: 05/06/2024] [Accepted: 05/11/2024] [Indexed: 05/19/2024]
Abstract
Alzheimer's disease (AD) is the most common type of cognitive impairment. AD is closely related to orthopedic diseases, such as osteoporosis and osteoarthritis, in terms of epidemiology and pathogenesis. Brain and bone tissues can regulate each other in different manners through bone-brain axis. This article reviews the research progress of the relationship between AD and orthopedic diseases, bone-brain axis mechanisms of AD, and AD therapy by targeting bone-brain axis, in order to deepen the understanding of bone-brain communication, promote early diagnosis and explore new therapy for AD patients.
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Affiliation(s)
- Fan Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Wei Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
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Guo X, Yang YY, Zhou R, Tian G, Shan C, Liu JM, Li R. Causal effect of blood osteocalcin on the risk of Alzheimer's disease and the mediating role of energy metabolism. Transl Psychiatry 2024; 14:205. [PMID: 38769320 PMCID: PMC11106250 DOI: 10.1038/s41398-024-02924-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 05/22/2024] Open
Abstract
Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of Alzheimer's disease (AD). However, the causality of these associations and the underlying mechanisms remain uncertain. We utilized a Mendelian randomization (MR) approach to investigate the causal effects of blood OCN levels on AD and to assess the potential involvement of glucose and lipid metabolism. Independent instrumental variables strongly associated (P < 5E-08) with blood OCN levels were obtained from three independent genome-wide association studies (GWAS) on the human blood proteome (N = 3301 to 35,892). Two distinct summary statistics datasets on AD from the International Genomics of Alzheimer's Project (IGAP, N = 63,926) and a recent study including familial-proxy AD patients (FPAD, N = 472,868) were used. Summary-level data for fasting glucose (FG), 2h-glucose post-challenge, fasting insulin, HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol (TC), and triglycerides were incorporated to evaluate the potential role of glucose and lipid metabolism in mediating the impact of OCN on AD risk. Our findings consistently demonstrate a significantly negative correlation between genetically determined blood OCN levels and the risk of AD (IGAP: odds ratio [OR, 95%CI] = 0.83[0.72-0.96], P = 0.013; FPAD: OR = 0.81 [0.70-0.93], P = 0.002). Similar estimates with the same trend direction were obtained using other statistical approaches. Furthermore, employing multivariable MR analysis, we found that the causal relationship between OCN levels and AD was disappeared after adjustment of FG and TC (IGAP: OR = 0.97[0.80-1.17], P = 0.753; FPAD: OR = 0.98 [0.84-1.15], P = 0.831). There were no apparent instances of horizontal pleiotropy, and leave-one-out analysis showed good stability of the estimates. Our study provides evidence supporting a protective effect of blood OCN levels on AD, which is primarily mediated through regulating FG and TC levels. Further studies are warranted to elucidate the underlying physio-pathological mechanisms.
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Affiliation(s)
- Xingzhi Guo
- Department of Geriatric Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
- Department of Geriatric Neurology, the Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi, China
| | - Yu-Ying Yang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
| | - Rong Zhou
- Department of Geriatric Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
- Department of Geriatric Neurology, the Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi, China
| | - Ge Tian
- Department of Geriatric Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China
| | - Chang Shan
- Department of Endocrinology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China
| | - Jian-Min Liu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
| | - Rui Li
- Department of Geriatric Neurology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China.
- Department of Geriatric Neurology, the Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi, China.
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Gao F, Pan R, Fan T, Liu L, Pan H. Identification of heel bone mineral density as a risk factor of Alzheimer's disease by analyzing large-scale genome-wide association studies datasets. Front Cell Dev Biol 2023; 11:1247067. [PMID: 38099291 PMCID: PMC10720361 DOI: 10.3389/fcell.2023.1247067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 11/06/2023] [Indexed: 12/17/2023] Open
Abstract
Introduction: Both low bone mineral density (BMD) and Alzheimer's disease (AD) commonly co_occur in the older adult. Until now, the association between AD and BMD has been widely reported by observational studies. However, Mendelian randomization (MR) studies did not support the causal association between BMD and AD. We think that the lack of significant causal association between AD and BMD identified by recent MR studies may be caused by small number of potential instrumental variables. Methods: We conduct a MR study to evaluate the causal effect of heel BMD on the risk of AD using 1,362 genome-wide significant and independent (p < 5.00E-08) heel BMD genetic variants as the potential instrumental variables, which are identified by a large-scale genome wide association study (GWAS) of heel BMD in 394,929 UK Biobank individuals. Using these 1,362 genome-wide significant and independent heel BMD genetic variants, we extracted their corresponding AD GWAS summary results in IGAP AD GWAS dataset (n = 63,926) and FinnGen AD GWAS dataset (n = 377,277). Five methods including inverse-variance weighted meta-analysis (IVW), weighted median, MR-Egger, MR-PRESSO, and MRlap were selected to perform the MR analysis. 951 of these 1,362 genetic variants are available in AD GWAS dataset. Results: We observed statistically significant causal effect of heel BMD on the risk of AD using IVW in IGAP AD GWAS dataset (OR = 1.048, 95%CI: 1.002-1.095, p = 0.04) and FinnGen AD GWAS dataset (OR = 1.053, 95% CI:1.011-1.098, p = 0.011). Importantly, meta-analysis of IVW estimates from IGAP and FinnGen further supported the causal effect of heel BMD on the risk of AD (OR = 1.051, 95% CI: 1.02-1.083, p = 0.0013). Discussion: Collectively, our current MR study supports heel BMD to be a risk factor of AD by analyzing the large-scale heel BMD and AD GWAS datasets. The potential mechanisms underlying the association between heel BMD and AD should be further evaluated in future.
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Affiliation(s)
- Feng Gao
- Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rongrong Pan
- Department of Orthopedics, Huangshan People’s Hospital, Huangshan, China
| | - Taixuan Fan
- Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lingling Liu
- Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Haile Pan
- Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Liu W, Hu Q, Zhang F, Shi K, Wu J. Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study. Heliyon 2023; 9:e21073. [PMID: 37916108 PMCID: PMC10616355 DOI: 10.1016/j.heliyon.2023.e21073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 08/03/2023] [Accepted: 10/13/2023] [Indexed: 11/03/2023] Open
Abstract
Objective Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. Methods Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy. Results The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688-0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744-0.985; P = 0.030). Conclusions Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications.
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Affiliation(s)
- Wangmi Liu
- The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Qiang Hu
- Pujiang Tianxian Orthopedic Hospital, Jinhua, 322200, China
| | - Feng Zhang
- The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Kesi Shi
- The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Jiayan Wu
- Department of Neurology, Chongming Branch, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 66 East Xiangyang Road, Chongming, Shanghai, China
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11
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Duan R, Hong CG, Chen ML, Wang X, Pang ZL, Xie H, Liu ZZ. Targeting autophagy receptors OPTN and SQSTM1 as a novel therapeutic strategy for osteoporosis complicated with Alzheimer's disease. Chem Biol Interact 2023; 377:110462. [PMID: 36958424 DOI: 10.1016/j.cbi.2023.110462] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/16/2023] [Accepted: 03/19/2023] [Indexed: 03/25/2023]
Abstract
Alzheimer's disease (AD) is a common degenerative disease among the elderly population. In addition to cognitive impairment, AD is often accompanied by behavioral manifestations. However, little attention has been paid to changes in bone metabolism and related mechanisms in patients with AD. We found that AD mice (APPswe/PS1dE9) had reduced bone density, weakened bone strength, and amyloid beta (Aβ) deposition in the bone tissue. It was further found that targeting autophagy receptors Optineurin (OPTN) and Sequestosome 1 (SQSTM1) increased bone density and bone strength in AD mice, promoted the clearance of Aβ in the bone tissue, and maintained bone homeostasis. Our study suggests that abnormal Aβ deposition may be the co-pathogenesis of AD and osteoporosis (OP). Targeting OPTN and SQSTM1 has a dual-functional effect of alleviating both AD and OP through selective autophagy that specifically targets Aβ for clearance. Therapeutic strategies targeting autophagy may help guide the treatment of patients with AD complicated with OP.
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Affiliation(s)
- Ran Duan
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Chun-Gu Hong
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Meng-Lu Chen
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Xin Wang
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhi-Lin Pang
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Hui Xie
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
| | - Zheng-Zhao Liu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
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Alzheimer's Disease and Impaired Bone Microarchitecture, Regeneration and Potential Genetic Links. Life (Basel) 2023; 13:life13020373. [PMID: 36836731 PMCID: PMC9963274 DOI: 10.3390/life13020373] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/08/2023] [Accepted: 01/16/2023] [Indexed: 02/03/2023] Open
Abstract
Alzheimer's Disease (AD) and osteoporosis are both age-related degenerative diseases. Many studies indicate that these two diseases share common pathogenesis mechanisms. In this review, the osteoporotic phenotype of AD mouse models was discussed, and shared mechanisms such as hormonal imbalance, genetic factors, similar signaling pathways and impaired neurotransmitters were identified. Moreover, the review provides recent data associated with these two diseases. Furthermore, potential therapeutic approaches targeting both diseases were discussed. Thus, we proposed that preventing bone loss should be one of the most important treatment goals in patients with AD; treatment targeting brain disorders is also beneficial for osteoporosis.
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Hu H, Mei J, Cai Y, Ding H, Niu S, Zhang W, Fang X. No genetic causal association between Alzheimer's disease and osteoporosis: A bidirectional two-sample Mendelian randomization study. Front Aging Neurosci 2023; 15:1090223. [PMID: 36761181 PMCID: PMC9905740 DOI: 10.3389/fnagi.2023.1090223] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
Objective Many observational studies have found an association between Alzheimer's disease (AD) and osteoporosis. However, it is unclear whether there is causal genetic between osteoporosis and AD. Methods A two-sample Mendelian randomization (MR) study was used to investigate whether there is a causal relationship between osteoporosis and AD. Genes for osteoporosis and AD were obtained from published the genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) with significant genome-wide differences (p < 5 × 10-8) and independent (r 2 < 0.001) were selected, and SNPs with F ≥ 10 were further analyzed. Inverse variance weighted (IVW) was used to assess causality, and the results were reported as odds ratios (ORs). Subsequently, heterogeneity was tested using Cochran's Q test, pleiotropy was tested using the MR-Egger intercept, and leave-one-out sensitivity analysis was performed to assess the robustness of the results. Results Using the IVW method, MR Egger method, and median-weighted method, we found that the results showed no significant causal effect of osteoporosis at different sites and at different ages on AD, regardless of the removal of potentially pleiotropic SNPs. The results were similar for the opposite direction of causality. These results were confirmed to be reliable and stable by sensitivity analysis. Conclusion This study found that there is no bidirectional causal relationship between osteoporosis and AD. However, they share similar pathogenesis and pathways.
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Affiliation(s)
- Hongxin Hu
- Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China,Department of Orthopedic Surgery, Affiliated Hospital of Putian University, Putian, China
| | - Jian Mei
- Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yuanqing Cai
- Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi, China
| | - Haiqi Ding
- Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Susheng Niu
- Key Laboratory of Orthopedics and Traumatology of Traditional Chinese Medicine and Rehabilitation Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Wenming Zhang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China,*Correspondence: Wenming Zhang, ✉
| | - Xinyu Fang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China,Xinyu Fang, ✉
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LLabre JE, Gil C, Amatya N, Lagalwar S, Possidente B, Vashishth D. Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer's Disease. J Bone Miner Res 2022; 37:2548-2565. [PMID: 36250342 PMCID: PMC9772191 DOI: 10.1002/jbmr.4723] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 10/03/2022] [Accepted: 10/14/2022] [Indexed: 12/31/2022]
Abstract
Alzheimer's disease (AD) patients present with symptoms such as impairment of insulin signaling, chronic inflammation, and oxidative stress. Furthermore, there are comorbidities associated with AD progression. For example, osteoporosis is common with AD wherein patients exhibit reduced mineralization and a risk for fragility fractures. However, there is a lack of understanding on the effects of AD on bone beyond loss of bone density. To this end, we investigated the effects of AD on bone quality using the 5XFAD transgenic mouse model in which 12-month-old 5XFAD mice showed accumulation of amyloid-beta (Aβ42) compared with wild-type (WT) littermates (n = 10/group; 50% female, 50% male). Here, we observed changes in cortical bone but not in cancellous bone quality. Both bone mass and bone quality, measured in femoral samples using imaging (micro-CT, confocal Raman spectroscopy, X-ray diffraction [XRD]), mechanical (fracture tests), and chemical analyses (biochemical assays), were altered in the 5XFAD mice compared with WT. Micro-CT results showed 5XFAD mice had lower volumetric bone mineral density (BMD) and increased endocortical bone loss. XRD results showed decreased mineralization with smaller mineral crystals. Bone matrix compositional properties, from Raman, showed decreased crystallinity along with higher accumulation of glycoxidation products and glycation products, measured biochemically. 5XFAD mice also demonstrated loss of initiation and maximum toughness. We observed that carboxymethyl-lysine (CML) and mineralization correlated with initiation toughness, whereas crystal size and pentosidine (PEN) correlated with maximum toughness, suggesting bone matrix changes predominated by advanced glycation end products (AGEs) and altered/poor mineral quality explained loss of fracture toughness. Our findings highlight two pathways to skeletal fragility in AD through alteration of bone quality: (i) accumulation of AGEs; and (ii) loss of crystallinity, decreased crystal size, and loss of mineralization. We observed that the accumulation of amyloidosis in brain correlated with an increase in several AGEs, consistent with a mechanistic link between elevated Aβ42 levels in the brain and AGE accumulation in bone. © 2022 American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Joan E. LLabre
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA
- Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA
| | - Cristianel Gil
- Department of Biology, Skidmore College, Saratoga Springs, NY, USA
| | - Neha Amatya
- Department of Biology, Skidmore College, Saratoga Springs, NY, USA
| | - Sarita Lagalwar
- Neuroscience Program, Skidmore College, Saratoga Springs, NY, USA
| | | | - Deepak Vashishth
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA
- Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA
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Kim DS, Zhang T, Park S. Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer's disease model. PHARMACEUTICAL BIOLOGY 2022; 60:212-224. [PMID: 35076339 PMCID: PMC8794073 DOI: 10.1080/13880209.2022.2025860] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 12/16/2021] [Accepted: 12/31/2021] [Indexed: 06/14/2023]
Abstract
CONTEXT Fruits of Forsythia suspensa Vahl (Oleaceae) and seeds of Cassia obtusifolia Linne (Caesalpinaceae) have been used to treat inflammation in Asia. OBJECTIVE We examined the alleviation of memory function in Alzheimer's disease (AD) rats fed Forsythiae Fructus (FF) and Cassiae Semen water extracts (CS) and investigated the mechanisms responsible for the effects. MATERIALS AND METHODS Thirty Sprague-Dawley male rats had hippocampal infusions of amyloid-β(25-35) (AD rats; memory deficit), and ten rats were infused with amyloid-β(35-25) (non-AD rats; no memory deficit). For eight weeks, all rats freely consumed high-fat diets (43% lard) incorporated with 200 mg/kg body weight assigned aqueous herbal extracts: AD-FF, AD-CS, or without extracts AD-CON (control), non-AD (normal-control). RESULTS Memory impairment was prevented in the AD-FF (0.54 ± 0.06-fold) and the AD-CS rats (0.33 ± 0.04-fold) compared to the AD-CON by inhibiting amyloid-β deposition to the levels less than one-fourth of the AD-CON group. The hippocampal pAkt→pGSK-3β→pFOXO1 pathway was attenuated by approximately 3.25-fold in the AD-CON, while AD-FF prevented the attenuation better than AD-CS. The relative intensity of hippocampal tau protein based on β-actin was suppressed with AD-FF (0.68 ± 0.09) and AD-CS (0.96 ± 0.81), compared to AD-CON (1.19 ± 0.13). AD decreased the abundance of Bacteroidales by 34.2% and Lactobacillales by 23.8% and increased Clostridiales by 181% while the AD-FF, but not the AD-CS, normalised the gut microbiota changes to be similar to the non-AD. DISCUSSION AND CONCLUSIONS FF improved memory deficits better than CS in an AD-induced rat model. The potential neuroprotective benefits of FF against AD may be applicable to human AD therapy with additional clinical research.
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Affiliation(s)
- Da Sol Kim
- Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea
| | - Ting Zhang
- Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea
| | - Sunmin Park
- Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea
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16
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Gong X, Zhang H, Liu X, Liu Y, Liu J, Fapohunda FO, Lü P, Wang K, Tang M. Is liquid biopsy mature enough for the diagnosis of Alzheimer's disease? Front Aging Neurosci 2022; 14:977999. [PMID: 35992602 PMCID: PMC9389010 DOI: 10.3389/fnagi.2022.977999] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 07/18/2022] [Indexed: 01/10/2023] Open
Abstract
The preclinical diagnosis and clinical practice for Alzheimer's disease (AD) based on liquid biopsy have made great progress in recent years. As liquid biopsy is a fast, low-cost, and easy way to get the phase of AD, continual efforts from intense multidisciplinary studies have been made to move the research tools to routine clinical diagnostics. On one hand, technological breakthroughs have brought new detection methods to the outputs of liquid biopsy to stratify AD cases, resulting in higher accuracy and efficiency of diagnosis. On the other hand, diversiform biofluid biomarkers derived from cerebrospinal fluid (CSF), blood, urine, Saliva, and exosome were screened out and biologically verified. As a result, more detailed knowledge about the molecular pathogenesis of AD was discovered and elucidated. However, to date, how to weigh the reports derived from liquid biopsy for preclinical AD diagnosis is an ongoing question. In this review, we briefly introduce liquid biopsy and the role it plays in research and clinical practice. Then, we summarize the established fluid-based assays of the current state for AD diagnostic such as ELISA, single-molecule array (Simoa), Immunoprecipitation-Mass Spectrometry (IP-MS), liquid chromatography-MS, immunomagnetic reduction (IMR), multimer detection system (MDS). In addition, we give an updated list of fluid biomarkers in the AD research field. Lastly, the current outstanding challenges and the feasibility to use a stand-alone biomarker in the joint diagnostic strategy are discussed.
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Affiliation(s)
- Xun Gong
- Department of Rheumatology and Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Hantao Zhang
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Xiaoyan Liu
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Yi Liu
- School of Life Sciences, Jiangsu University, Zhenjiang, China
- Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing, China
| | - Junlin Liu
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | | | - Peng Lü
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Kun Wang
- Children’s Center, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Min Tang
- School of Life Sciences, Jiangsu University, Zhenjiang, China
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Zhang P, Zhou Y, Chen G, Li J, Wang B, Lu X. Potential association of bone mineral density loss with cognitive impairment and central and peripheral amyloid-β changes: a cross-sectional study. BMC Musculoskelet Disord 2022; 23:626. [PMID: 35773707 PMCID: PMC9245236 DOI: 10.1186/s12891-022-05580-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 06/21/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND There is some evidence in the literature that older adults with cognitive impairments have a higher risk for falls and osteoporotic hip fractures. Currently, the associations between bone health and cognitive health have not been extensively studied. Thus, the present cross-sectional study aims to investigate the relationship between markers of bone loss and cognitive performance in older adults with and without osteopenia as well as older adults with cognitive impairments (i.e., Alzheimer's disease [AD]). METHODS Sixty-two non-osteopenia participants and one hundred three osteopenia participants as the cohort 1 and 33 cognitively normal non-AD participants and 39 AD participants as the cohort 2 were recruited. To assess cognitive and bone health, hip bone mineral density (BMD) and cognitive performance (via Minimal Mental State Examination [MMSE] and/or Auditory Verbal Learning Test-delayed recall [AVLT-DR]) were assessed. Furthermore, in cohort 1, plasma amyloid-β (Aβ) levels, and in cohort 2, cerebrospinal fluid (CSF) Aβ levels were determined. RESULTS We observed that (1) compared with non-osteopenia participants, BMD values (t = - 22.806; 95%CI: - 1.801, - 1.484; p < 0.001), MMSE scores (t = - 5.392; 95%CI: - 3.260, - 1.698; p < 0.001), and AVLT-DR scores (t = - 4.142; 95%CI: - 2.181, - 0.804; p < 0.001), plasma Aβ42 levels (t = - 2.821; 95%CI: - 1.737, - 0.305; p = 0.01), and Aβ42/40 ratio (t = - 2.020; 95%CI: - 0.009, - 0.001; p = 0.04) were significantly lower in osteopenia participants; (2) plasma Aβ42/40 ratio showed a mediate effect for the association between BMD values and the performance of cognitive function in osteopenia participants by mediation analysis, adjusting age, sex, years of education, and body mass index (BMI); (3) BMD values (95%CI: - 1.085, 0.478; p < 0.001) were significantly reduced in AD participants as compared with cognitively normal non-AD participants; (4) in AD participants, the interactive effects of BMD and CSF Aβ42/40 ratio on MMSE scores was found by regression analysis, controlling age, sex, years of education, and BMI; (5) BMD can distinguish AD participants from cognitively normal non-AD participants with AUC of 0.816 and distinguish participants with the cognitive impairment from cognitively normal participants with AUC of 0.794. CONCLUSION Our findings suggest a relationship between bone health and cognitive health. Given the correlations between BMD and important markers of cognitive health (e.g., central and peripheral pathological change of Aβ), BMD might serve as a promising and easy-accessible biomarker. However, more research is needed to further substantiate our findings.
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Affiliation(s)
- Peng Zhang
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China
| | - Yi Zhou
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China
| | - Gang Chen
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China
| | - Jun Li
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China
| | - Bangjun Wang
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China
| | - Xinyan Lu
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang, 441021, China.
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Kumar S, Chandnani A, Aung NH, Shahid S, Bukhari D, Shahzad S, Kumar B, Memon S. Alzheimer's Disease and Its Association With Bone Health: A Case-Control Study. Cureus 2021; 13:e13772. [PMID: 33842148 PMCID: PMC8027098 DOI: 10.7759/cureus.13772] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2021] [Indexed: 11/05/2022] Open
Abstract
Introduction Alzheimer's disease is associated with low bone mineral density. Various studies have linked early-onset Alzheimer's disease with bone health. In this study, we will determine the association between bone health and recently diagnosed Alzheimer's disease in the local population. Methods This case-control study was conducted at the neurology unit from April 2019 to Sept 2019. One hundred and fifty (150) Alzheimer's patients with recently (within the last six months) confirmed diagnoses, based on clinical symptoms, mental status, and computed tomography (CT) scan, were included from the neurology outpatient department. The gender and age-matched 150 healthy participants were included in the study as the reference group. Various parameters of bone health and mental status were measured. Results Participants with Alzheimer's had a significantly lower level of serum vitamin D (15.2 ± 4.2 ng/mL vs. 27.5 ± 8.1 ng/mL, p-value: < 0.0001) and lower level of serum osteocalcin (4.3 ± 1.7 ng/L vs. 5.6 ± 2.0 ng/L, p-value: < 0.0001). Participants with Alzheimer's disease had more people with T-score ≤ -2.5 as compared to the general population (52.0% vs. 16.6%, p-value <0.0001). Conclusion Alzheimer's disease is associated with poor bone health as compared to the general population of the same age. Bone health can be an important parameter to screen patients at risk of Alzheimer's disease. The management of Alzheimer's disease should include a regular assessment of bone health, and the treatment plan should include therapies to improve bone health.
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Affiliation(s)
- Sameet Kumar
- Internal Medicine, Chandka Medical College, Karachi, PAK
| | - Aakash Chandnani
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Norah H Aung
- Health Sciences, Western Illinois University, Macomb, USA
- Internal Medicine, University of Medicine 1, Yangon, MMR
| | - Simra Shahid
- Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Dua Bukhari
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Sania Shahzad
- Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Besham Kumar
- Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Sidra Memon
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
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Effects of 6-Month Multimodal Physical Exercise Program on Bone Mineral Density, Fall Risk, Balance, and Gait in Patients with Alzheimer's Disease: A Controlled Clinical Trial. Brain Sci 2021; 11:brainsci11010063. [PMID: 33419016 PMCID: PMC7825330 DOI: 10.3390/brainsci11010063] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 12/14/2022] Open
Abstract
We aimed to determine the short- and medium-term effects of a multimodal physical exercise program (MPEP) on bone health status, fall risk, balance, and gait in patients with Alzheimer’s disease. A single-blinded, controlled clinical trial was performed where 72 subjects were allocated in a 3:1 ratio to an intervention group (IG; n = 53) and control group (CG; n = 19), where the IG’s subjects were admitted to live in a State Reference Center of Alzheimer’s disease, which offers the targeted exercise program, while the CG’s subjects resided in independent living. A multidisciplinary health team assessed all patients before allocation, and dependent outcomes were again assessed at one, three, and six months. During the study, falls were recorded, and in all evaluations, bone mineral density was measured using a calcaneal quantitative ultrasound densitometer; balance and gait were measured using the performance-oriented mobility assessment (POMA), the timed up and go test (TUG), the one-leg balance test (OLB), and the functional reach test (FR). There were no differences between groups at baseline for all outcome measures. The prevalence of falls was significantly lower in the IG (15.09%) than in the CG (42.11%) (χ2 = 5.904; p = 0.015). We also found that there was a significant time*group interaction, with a post hoc Šidák test finding significant differences of improved physical function, especially in gait, for the IG, as assessed by POMA-Total, POMA-Gait, and TUG with a large effect size (ƞ2p = 0.185–0.201). In balance, we found significant differences between groups, regardless of time, and a medium effect size as assessed by POMA-Balance and the OLB (ƞ2p = 0.091–0.104). Clinically relevant effects were observed, although without significant differences in bone health, with a slowing of bone loss. These results show that a multimodal physical exercise program reduces fall risk and produces an improvement in gait, balance, and bone mineral density in the short and medium term in institutionalized patients with Alzheimer’s disease.
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Puente-González AS, Sánchez-González F, Hernández-Xumet JE, Sánchez-Sánchez MC, Barbero-Iglesias FJ, Méndez-Sánchez R. Short and medium-term effects of a multicomponent physical exercise program with a Mediterranean diet on bone mineral density, gait, balance, and fall risk for patients with Alzheimer disease: Randomized controlled clinical trial study protocol. Medicine (Baltimore) 2020; 99:e22385. [PMID: 32957420 PMCID: PMC7505369 DOI: 10.1097/md.0000000000022385] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
INTRODUCTION Reduced bone mineral density and increased risk of falls are related with Alzheimer disease, and these increase likelihood of bone osteoporotic fractures causing serious complications such as disability, fear of falling, loss autonomy, decreased quality of life, and anticipated mortality in elderly patients. Gait and balance disturb are 2 factors to favor falls in elderly, and in patients with cognitive impairment, the risk of falls increases to double. Exercise and Mediterranean diet produce beneficial effects for aging, cognitive decline, and are widely recommended to reduce the effects of osteoporosis, fall risk, and related fragility fractures. The primary objective of this study is to evaluate the short and medium-term effects during 6 months, of a multicomponent physical exercise program with a Mediterranean diet on bone mineral density, fall risk, balance, and gait by a controlled clinical trial in patients with Alzheimer disease. METHODS The study is a 6-month, randomized controlled parallel-group, single-blinded clinical trial. Institutionalized patients with Alzheimer disease will be included. The intervention group will perform a multicomponent physical exercise program in reduced groups, with a frequency of 3 sessions per week, associated with a Mediterranean diet. This program includes strength, balance, and aerobic resistance exercises, and in the main part of the session, also ludic exercises to improve agility, coordination, and balance. The control group will receive usual care. The outcomes to assess are the change of physical functions, such as gait and balance, and the change of bone mineral density by calcaneal quantitative ultrasound, during the study follow-up at 1, 3, and 6 months. This clinical trial will generate more and new evidence on the effects of a multicomponent physical exercise program and Mediterranean diet in patients with Alzheimer disease on risk of falls and osteoporotic fractures, the relation of these with bone mineral density, gait and balance, and the correlations between them. ETHICS AND DISSEMINATION This study protocol has been approved by the Ethics Committee of the University of Salamanca. The results will be published in peer-reviewed journals and disseminated in national and international conferences, to the participants and their families, and the general public through the associations of people with AD. TRIAL REGISTRATION ID ClínicalTrials.gov ID: NCT04439097.
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Affiliation(s)
- Ana Silvia Puente-González
- Department of Nursing and Physical Therapy. University of Salamanca, Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
| | | | | | - María Carmen Sánchez-Sánchez
- Department of Nursing and Physical Therapy. University of Salamanca, Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
| | - Fausto José Barbero-Iglesias
- Department of Nursing and Physical Therapy. University of Salamanca, Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
| | - Roberto Méndez-Sánchez
- Department of Nursing and Physical Therapy. University of Salamanca, Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
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