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Mansel C, Mazzotti DR, Townley R, Sardiu ME, Swerdlow RH, Honea RA, Veatch OJ. Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease. Alzheimers Dement 2025; 21:e70017. [PMID: 40110639 PMCID: PMC11923574 DOI: 10.1002/alz.70017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/10/2025] [Accepted: 01/26/2025] [Indexed: 03/22/2025]
Abstract
INTRODUCTION Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis. METHODS Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years. RESULTS Two thousand seven hundred fifty-four individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow-up period (p = 0.013). DISCUSSION Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials. HIGHLIGHTS Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset. Three problem history subtypes were found: minimal, substance use, and cardiovascular. The mean change in Clinical Dementia Rating Sum of Boxes (CDR-SB) was assessed over a 2 year follow-up. The cardiovascular subtype was associated with the worst cognitive decline. The magnitude of change in CDR-SB was similar to recent AD clinical trials.
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Affiliation(s)
- Clayton Mansel
- Department of Cell Biology and PhysiologyUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Diego R. Mazzotti
- Department of Internal MedicineDivision of Medical InformaticsDivision of Pulmonary Critical Care and Sleep MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Ryan Townley
- Alzheimer's Disease Research CenterUniversity of Kansas Medical CenterFairwayKansasUSA
| | - Mihaela E. Sardiu
- Department of Biostatistics and Data ScienceUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Russell H. Swerdlow
- Alzheimer's Disease Research CenterUniversity of Kansas Medical CenterFairwayKansasUSA
| | - Robyn A. Honea
- Alzheimer's Disease Research CenterUniversity of Kansas Medical CenterFairwayKansasUSA
| | - Olivia J. Veatch
- Department of Cell Biology and PhysiologyUniversity of Kansas Medical CenterKansas CityKansasUSA
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Mansel C, Mazzotti DR, Townley R, Sardiu ME, Swerdlow RH, Honea RA, Veatch OJ. Distinct medical and substance use histories associate with cognitive decline in Alzheimer's Disease. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.11.26.24317918. [PMID: 39649607 PMCID: PMC11623748 DOI: 10.1101/2024.11.26.24317918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2024]
Abstract
INTRODUCTION Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's Disease (AD) diagnosis. METHODS Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Centers (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over two years. RESULTS 2754 individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336) subtypes. The cardiovascular problem history subtype had significantly worse cognitive decline over a two-year follow-up period (p = 0.013). DISCUSSION Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.
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Affiliation(s)
- Clayton Mansel
- Department of Cell Biology and Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160
| | - Diego R Mazzotti
- Department of Internal Medicine, Division of Medical Informatics, Division of Pulmonary Critical Care and Sleep Medicine, University of Kansas Medical Center, Kansas City, KS 66160
| | - Ryan Townley
- Alzheimer's Disease Research Center, University of Kansas Medical Center, 4350 Shawnee Mission Pkwy, Mail Stop 6002, Fairway, KS, 66205
| | - Mihaela E Sardiu
- Department of Biostatistics and Data Science, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160
| | - Russell H Swerdlow
- Alzheimer's Disease Research Center, University of Kansas Medical Center, 4350 Shawnee Mission Pkwy, Mail Stop 6002, Fairway, KS, 66205
| | - Robyn A Honea
- Alzheimer's Disease Research Center, University of Kansas Medical Center, 4350 Shawnee Mission Pkwy, Mail Stop 6002, Fairway, KS, 66205
| | - Olivia J Veatch
- Department of Cell Biology and Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160
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Lee J, Kim J, An SJ. Association of diabetes risk with changes in memory, working memory, and processing speed among older adults. Front Psychol 2024; 15:1427139. [PMID: 39600601 PMCID: PMC11588497 DOI: 10.3389/fpsyg.2024.1427139] [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: 05/03/2024] [Accepted: 09/30/2024] [Indexed: 11/29/2024] Open
Abstract
Background This study investigated the risk of diabetes by examining changes in memory, working memory, and processing speed among older adults to provide evidence on how each cognitive domain is associated with the risk of diabetes in older adults. Methods This study used Health and Retirement Study data and tracked the respondents from 2012 to 2020 (n = 5,748). The Telephone Interview for Cognitive Status-27 includes three cognitive tests (recall, seven subtraction, and counting backward tests) to assess each cognitive domain. A Cox proportional hazard regression was used to calculate the changes in the odds ratio (OR) of diabetes by increasing each cognitive function and the parameter in covariates. Results We found that the OR of diabetes decreased with increasing universal cognitive function, increasing memory, working memory, and processing speed, and that age increased the OR in all analysis models. Conclusion The findings of this study contribute to filling gaps in the literature by exploring: (a) the association between each cognitive function and the decline in diabetes risk and (b) the varying patterns of change in diabetes risk with increasing cognitive function.
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Affiliation(s)
- Jungjoo Lee
- School of Health Professions, College of Nursing and Health Professions, University of Southern Mississippi, Hattiesburg, MS, United States
| | - Junhyoung Kim
- Department of Health Behavior, School of Public Health, Texas A&M University, College Station, TX, United States
| | - Sang Joon An
- Department of Neurology, The Convergence Institute of Healthcare and Medical Science, International St. Mary’s Hospital, Catholic Kwandong University, Incheon, Republic of Korea
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Sadier NS, El Hajjar F, Al Sabouri AAK, Abou-Abbas L, Siomava N, Almutary AG, Tambuwala MM. Irisin: An unveiled bridge between physical exercise and a healthy brain. Life Sci 2024; 339:122393. [PMID: 38176582 DOI: 10.1016/j.lfs.2023.122393] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 12/18/2023] [Accepted: 12/25/2023] [Indexed: 01/06/2024]
Abstract
AIMS Physical exercise has been widely recognized for its positive effects on health and well-being. Recently, the impact of exercise on the nervous system has gained attention, with evidence indicating improvements in attention, memory, neurogenesis, and the release of "happiness hormones." One potential mediator of these benefits is Irisin, a myokine induced by exercise that can cross the blood-brain barrier, reduce neuroinflammation, and counteract neurodegeneration. The objective of this study is to conduct a systematic review of animal trials to summarize the neuroprotective effects of Irisin injection in mitigating neuroinflammation and neurodegeneration. MATERIALS AND METHODS Two independent reviewers screened three databases (PubMed, Embase, and Google Scholar) in November 2022. Animal studies assessing the neuroprotective effects of Irisin in mitigating neuroinflammation or counteracting neurodegeneration were included. The methodological quality of the included studies was assessed using SYRCLE's Risk of Bias tool. KEY FINDINGS Twelve studies met the inclusion criteria. Irisin injection in rodents significantly reduced neuroinflammation, cytokine cascades, and neurodegeneration. It also protected neurons from damage and apoptosis, reduced oxidative stress, blood-brain barrier disruption, and neurobehavioral deficits following disease or injury. Various mechanisms were suggested to be responsible for these neuroprotective effects. Most of the included studies presented a low risk of bias based on SYRCLE's Risk of Bias tool. Irisin injection demonstrated the potential to alleviate neuroinflammation and counteract neurodegeneration in rodent models through multiple pathways. However, further research is needed to fully understand its mechanism of action and its potential applications in clinical practice and drug discovery.
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Affiliation(s)
- Najwane Said Sadier
- College of Health Sciences, Abu Dhabi University, Al Ain Road, Abu Dhabi, PO Box 3838-111188, United Arab Emirates; Neurosciences Research Center, Faculty of Medical Sciences, Lebanese University, 275 Old Saida Road, Beirut, PO Box 6573/14, Lebanon.
| | - Farah El Hajjar
- Neurosciences Research Center, Faculty of Medical Sciences, Lebanese University, 275 Old Saida Road, Beirut, PO Box 6573/14, Lebanon.
| | - Amani Al Khayat Al Sabouri
- Neurosciences Research Center, Faculty of Medical Sciences, Lebanese University, 275 Old Saida Road, Beirut, PO Box 6573/14, Lebanon
| | - Linda Abou-Abbas
- Neurosciences Research Center, Faculty of Medical Sciences, Lebanese University, 275 Old Saida Road, Beirut, PO Box 6573/14, Lebanon; INSPECT-LB (Institut National de Santé Publique, d'Épidémiologie Clinique et de Toxicologie-Liban), Beirut, Lebanon.
| | - Natalia Siomava
- Department of Biology, Belarusian State University, Minsk, Belarus
| | - Abdulmajeed G Almutary
- College of Health Sciences, Abu Dhabi University, Al Ain Road, Abu Dhabi, PO Box 3838-111188, United Arab Emirates; Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Saudi Arabia.
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, England, United Kingdom; College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
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Si SC, Yang W, Luo HY, Ma YX, Zhao H, Liu J. Cognitive decline in elderly patients with type 2 diabetes is associated with glycated albumin, ratio of Glycated Albumin to glycated hemoglobin, and concentrations of inflammatory and oxidative stress markers. Heliyon 2023; 9:e22956. [PMID: 38058429 PMCID: PMC10696244 DOI: 10.1016/j.heliyon.2023.e22956] [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: 04/09/2023] [Revised: 10/14/2023] [Accepted: 11/22/2023] [Indexed: 12/08/2023] Open
Abstract
Objective To investigate the correlations of cognitive function with glycated albumin (GA), the ratio of GA to glycated hemoglobin (GA/HbA1c), and the concentrations of interleukin-6 (IL-6) and superoxide dismutase (SOD) in elderly patients with type 2 diabetes mellitus (T2DM). Methods A total of 44 elderly T2DM patients were evaluated for cognitive function using the mini-mental state examination (MMSE) and the Montreal cognitive assessment (MoCA). Patients were then divided into two groups based on the MMSE and MoCA scores: a cognitive dysfunction group and a normal cognitive function group. The correlations of the MMSE and MoCA scores with GA/HbA1c, GA, IL-6, and SOD were analyzed. Logistic regression analysis was used to identify independent influential factors for cognitive dysfunction. The predictive value of GA and GA/HbA1c for cognitive dysfunction in elderly T2DM patients was evaluated by receiver operating characteristic (ROC) curve analysis. Results Among these patients, 28 had cognitive impairment. They had significantly higher GA/HbA1c, increased GA and IL-6 levels, and lower SOD concentrations than the normal cognitive function group (all P < 0.05). GA/HbA1c was negatively correlated with the MMSE (r = -0.430, P = 0.007) and MoCA (r = -0.432, P = 0.007) scores. SOD was positively correlated with the MMSE (r = 0.585, P=0.014) and MoCA (r = 0.635, P=0.006) scores. IL-6 was negatively correlated with the MoCA score (r = -0.421, P=0.015). Age and GA/HbA1c were independent factors contributing to cognitive dysfunction. The areas under the ROC curves of GA and GA/HbA1c for the diagnosis of cognitive dysfunction were 0.712 and 0.720, respectively. Conclusions GA and GA/HbA1c are related to cognitive dysfunction in elderly patients with T2DM.
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Affiliation(s)
| | - Wei Yang
- Corresponding author. Xuanwu Hospital, Capital Medical University, China National Clinical Research Center for Geriatric Medicine, No. 45 Changchun Road, Beijing 100053, China.
| | - Hong-Yu Luo
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, China National Clinical Research Center for Geriatric Medicine, Beijing 100053, China
| | - Yi-Xin Ma
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, China National Clinical Research Center for Geriatric Medicine, Beijing 100053, China
| | - Huan Zhao
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, China National Clinical Research Center for Geriatric Medicine, Beijing 100053, China
| | - Jia Liu
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, China National Clinical Research Center for Geriatric Medicine, Beijing 100053, China
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Arora G, Milani C, Tanuseputro P, Tang P, Jeong A, Kobewka D, Webber C. Identifying predictors of cognitive decline in long-term care: a scoping review. BMC Geriatr 2023; 23:538. [PMID: 37670246 PMCID: PMC10478432 DOI: 10.1186/s12877-023-04193-6] [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: 01/22/2023] [Accepted: 07/24/2023] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Cognitive impairment can cause social, emotional, and financial burdens on individuals, caregivers, and healthcare providers. This is especially important in settings such as long-term care (LTC) homes which largely consist of vulnerable older adults. Thus, the objective of this study is to review and summarize current research examining risk factors of cognitive decline in older adults within LTC. METHODS This scoping review includes primary observational research studies assessing within-person change in cognition over time in LTC or equivalent settings in high resource countries. A mean participant age of ≥ 65 years was required. Searches were conducted in Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PyscInfo on June 27th, 2022 and included articles published during or after the year 2000. Title, abstract, and full-text screening was performed by two independent reviewers using Covidence. Specific predictors along with their associated relation with cognitive decline were extracted by a team of reviewers into a spreadsheet. RESULTS Thirty-eight studies were included in this review. The mean sample size was 14 620. Eighty-seven unique predictors were examined in relation to cognitive decline. Dementia was the most studied predictor (examined by 9 of 38 studies), and the most conclusive, with eight of those studies identifying it as a risk factor for cognitive decline. Other predictors that were identified as risk factors included arterial stiffness (identified by 2 of 2 studies), physical frailty (2 of 2 studies), sub-syndromal delirium (2 of 2 studies), and undergoing the first wave of COVID-19 lockdowns (2 of 2 studies). ADL independence was the most conclusive protective factor (3 of 4 studies), followed by social engagement (2 of 3 studies). Many remaining predictors showed no association and/or conflicting results. CONCLUSIONS Dementia was the most common risk factor, while ADL independence was the most common protective factor associated with cognitive decline in LTC residents. This information can be used to stratify residents by risk severity and provide better personalized care for older adults through the targeted management of cognitive decline.
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Affiliation(s)
| | | | | | - Patrick Tang
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
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Rajabi F, Rahimi S, Maracy MR, Barekatain M. Association between cognitive capacity and metabolic indices in patients with neuropsychiatric disorders. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2023; 12:292. [PMID: 37849862 PMCID: PMC10578545 DOI: 10.4103/jehp.jehp_82_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/11/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND Although previous studies suggested the relationship between metabolic indices and cognitive capacity, results have been conflicting. The prevalence of metabolic and cognitive disorders is high in patients with neuropsychiatric disorders. We aimed to assess the relationship between laboratory metabolic indices and specific areas of cognitive capacity. MATERIALS AND METHODS This was a retrospective review of the medical records of 423 from 452 patients with neuropsychiatric disorders who were admitted to the neuropsychiatry unit, Ayatollah Kashani Hospital, Isfahan, Iran, from September 1, 2018, to September 30, 2022. We extracted demographic factors, laboratory metabolic indices, and scores of the Neuropsychiatry Unit Cognitive Assessment tool (NUCOG). We utilized a generalized linear model (GLM) to demonstrate the effect of metabolic indices on the risk of reduction in cognitive domains. Due to the presence of missing data in the metabolic indices, we used the multiple imputation method. RESULTS The regression coefficient of NUCOG total score and subscale scores for metabolic indices using GLM after multiple imputation method demonstrated that among the metabolic indicators, fasting blood sugar (FBS) had the reverse relationship with the total score of NUCOG (β = -.05). Among the NUCOG subscales, executive functioning had the strongest relationship with FBS (β = -.01). Also, there was a negative relationship between patients' age and the total score of NUCOG (β = -.38). Educational level had a positive relationship with the total NUCOG score (β =10.2). CONCLUSIONS The main metabolic factors that might reduce cognitive capacity were higher FBS.
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Affiliation(s)
- Fatemeh Rajabi
- Department of Psychiatry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somayyeh Rahimi
- Department of Psychiatry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad R. Maracy
- Department of Epidemiology and Biostatistics, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Majid Barekatain
- Department of Psychiatry, Isfahan University of Medical Sciences, Isfahan, Iran
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Amiri P, Pirnejad H, Bahaadinbeigy K, Baghini MS, Khazaee PR, Niazkhani Z. A qualitative study of factors influencing ePHR adoption by caregivers and care providers of Alzheimer's patients: An extension of the unified theory of acceptance and use of technology model. Health Sci Rep 2023; 6:e1394. [PMID: 37425233 PMCID: PMC10323167 DOI: 10.1002/hsr2.1394] [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: 10/17/2022] [Revised: 05/06/2023] [Accepted: 06/21/2023] [Indexed: 07/11/2023] Open
Abstract
Background and Aims As the nowadays provision of many healthcare services relies on technology, a better understanding of the factors contributing to the acceptance and use of technology in health care is essential. For Alzheimer's patients, an electronic personal health record (ePHR) is one such technology. Stakeholders should understand the factors affecting the adoption of this technology for its smooth implementation, adoption, and sustainable use. So far, these factors have not fully been understood for Alzheimer's disease (AD)-specific ePHR. Therefore, the present study aimed to understand these factors in ePHR adoption based on the perceptions and views of care providers and caregivers involved in AD care. Methods This qualitative study was conducted from February 2020 to August 2021 in Kerman, Iran. Seven neurologists and 13 caregivers involved in AD care were interviewed using semi-structured and in-depth interviews. All interviews were conducted through phone contacts amid Covid-19 imposed restrictions, recorded, and transcribed verbatim. The transcripts were coded using thematic analysis based on the unified theory of acceptance and use of technology (UTAUT) model. ATLAS.ti8 was used for data analysis. Results The factors affecting ePHR adoption in our study comprised subthemes under the five main themes of performance expectancy, effort expectancy, social influence, facilitating conditions of the UTAUT model, and the participants' sociodemographic factors. From the 37 facilitating factors and 13 barriers identified for ePHR adoption, in general, the participants had positive attitudes toward the ease of use of this system. The stated obstacles were dependent on the participants' sociodemographic factors (such as age and level of education) and social influence (including concern about confidentiality and privacy). In general, the participants considered ePHRs efficient and useful in increasing neurologists' information about their patients and managing their symptoms in order to provide better and timely treatment. Conclusion The present study gives a comprehensive insight into the acceptance of ePHR for AD in a developing setting. The results of this study can be utilized for similar healthcare settings with regard to technical, legal, or cultural characteristics. To develop a useful and user-friendly system, ePHR developers should involve users in the design process to take into account the functions and features that match their skills, requirements, and preferences.
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Affiliation(s)
- Parastoo Amiri
- Student Research CommitteeKerman University of Medical SciencesKermanIran
| | - Habibollah Pirnejad
- Patient Safety Research Center, Clinical Research InstituteUrmia University of Medical SciencesUrmiaIran
- Erasmus School of Health Policy and ManagementErasmus University RotterdamRotterdamThe Netherlands
| | - Kambiz Bahaadinbeigy
- Medical Informatics Research Center, Institute of Futures Studies in HealthKerman University of Medical SciencesKermanIran
| | - Mahdie Shojaei Baghini
- Medical Informatics Research Center, Institute of Futures Studies in HealthKerman University of Medical SciencesKermanIran
| | | | - Zahra Niazkhani
- Nephrology and Kidney Transplant Research Center, Clinical Research InstituteUrmia University of Medical SciencesUrmiaIran
- Health Care Governance, Erasmus School of Health Policy and ManagementErasmus University RotterdamRotterdamThe Netherlands
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Li F, Kong X, Zhu H, Xu H, Wu B, Cao Y, Li J. The moderating effect of cognitive reserve on cognitive function in patients with Acute Ischemic Stroke. Front Aging Neurosci 2022; 14:1011510. [PMID: 36466605 PMCID: PMC9710856 DOI: 10.3389/fnagi.2022.1011510] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/31/2022] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Recovery of cognitive function after stroke has inter-individual variability. The theory of cognitive reserve offers a potential explanation of the variability in cognitive function after stroke. OBJECTIVE This study aimed to investigate the moderating effect of cognitive reserve on the relationship between the stroke severity and cognitive function after stroke. MATERIALS AND METHODS A total of 220 patients with Acute Ischemic Stroke (AIS) were recruited in 2021 from two stroke centers in Nanjing, China. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Cognitive Reserve Index questionnaire (CRIq) and validated Montreal Cognitive Assessment, Changsha Version (MoCA-CS) were used to assess cognitive reserve and cognitive function within 7 days after stroke onset, respectively. A series of multivariate linear regression models were applied to test the moderating effect of cognitive reserve. RESULTS Patients with a higher level of cognitive reserve had better cognitive function after stroke compared with those with a lower level of cognitive reserve (β = 0.074, p = 0.003). The interaction of NIHSS and cognitive reserve was statistically significant (β = -0.010, p = 0.045) after adjusting for some key covariates [e.g., age, marital status, Oxfordshire Community Stroke Project (OCSP) classification, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, cerebral vascular stenosis, diabetes and atrial fibrillation]. CONCLUSION Cognitive reserve may help to buffer the effect of stroke-related pathology on cognitive decline in Chinese acute stroke patients. Enhancing cognitive reserve in stroke patients may be one of the potential strategies for preventing vascular dementia.
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Affiliation(s)
- Fanfan Li
- School of Nursing, Naval Medical University, Shanghai, China
| | - Xiangjing Kong
- Air Force Hospital of Eastern Theater Command, Nanjing, China
| | - Huanzhi Zhu
- School of Nursing, Naval Medical University, Shanghai, China
| | - Hanzhang Xu
- School of Nursing, Duke University, Durham, NC, United States
- School of Medicine, Duke University, Durham, NC, United States
| | - Bei Wu
- Rory Meyers College of Nursing, New York University, New York, NY, United States
| | - Yanpei Cao
- Department of Nursing, Huashan Hospital, Fudan University, Shanghai, China
| | - Juan Li
- School of Nursing, Naval Medical University, Shanghai, China
- Department of Nursing, Huashan Hospital, Fudan University, Shanghai, China
- National Center for Neurological Disorders, Shanghai, China
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Bai Y, Xin M, Lin J, Xie J, Lin R, Peng Z, Guo J, Bai W. Banana starch intervention ameliorates diabetes-induced mood disorders via modulation of the gut microbiota-brain axis in diabetic rats. FOOD AGR IMMUNOL 2022. [DOI: 10.1080/09540105.2022.2071846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Yongliang Bai
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
- South China Research and Development Center for Food Safety, Foshan University, Foshan, People’s Republic of China
| | - Meiguo Xin
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
- South China Research and Development Center for Food Safety, Foshan University, Foshan, People’s Republic of China
| | - Junming Lin
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
| | - Jing Xie
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
| | - Roumin Lin
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
| | - Zhenshan Peng
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
| | - Jingwen Guo
- School of Food Science and Engineering, Foshan University, Foshan, People’s Republic of China
| | - Weidong Bai
- College of Food Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, People’s Republic of China
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Newby D, Garfield V. Understanding the inter-relationships of type 2 diabetes and hypertension with brain and cognitive health: A UK Biobank study. Diabetes Obes Metab 2022; 24:938-947. [PMID: 35112465 PMCID: PMC9415107 DOI: 10.1111/dom.14658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/13/2022] [Accepted: 01/30/2022] [Indexed: 01/28/2023]
Abstract
AIM To understand the impact of diabetes and co-morbid hypertension on cognitive and brain health. MATERIALS AND METHODS We used data from the UK Biobank cohort consisting of ~500 000 individuals aged 40 to 69 years. Our outcomes included brain structural magnetic resonance imaging variables and cognitive function tests in a maximum of 38 918 individuals. We firstly tested associations with all outcomes between those with diabetes (n = 2043) and without (n = 36 875) and, secondly, compared those with co-morbid diabetes/hypertension (n = 1283) with those with only diabetes (n = 760), hypertension (n = 9649) and neither disease (n = 27 226). Our analytical approach comprised linear regression models, with adjustment for a range of demographic and health factors. Standardized betas are reported. RESULTS Those with diabetes had worse brain and cognitive health for the majority of neuroimaging and cognitive measures, with the exception of g fractional anisotropy (white matter integrity), amygdala, pairs matching and tower rearranging. Compared with individuals with co-morbid diabetes and hypertension, those with only hypertension had better brain health overall, with the largest difference observed in the pallidum (β = .189, 95% CI = 0.241; 0.137), while those with only diabetes differed in total grey volume (β = .150, 95% CI = 0.122; 0.179). Individuals with only diabetes had better verbal and numeric reasoning (β = .129, 95% CI = 0.077; 0.261), whereas those with only hypertension performed better on the symbol-digit substitution task (β = .117, 95% CI = 0.048; 0.186). CONCLUSIONS Individuals with co-morbid diabetes and hypertension have worse brain and cognitive health compared with those with only one of these diseases. These findings potentially suggest that prevention of both diabetes and hypertension may delay changes in brain structure, as well as cognitive decline and dementia diagnosis.
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Affiliation(s)
- Danielle Newby
- Department of PsychiatryUniversity of Oxford, Warneford HospitalOxfordUK
| | - Victoria Garfield
- MRC Unit for Lifelong Health and Ageing at UCL, Department of Population Science and Experimental Medicine, Institute of Cardiovascular ScienceUniversity College LondonLondonUK
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Afzal M, Al-Abbasi FA, Kazmi I, Imam SS, Alshehri S, Ghoneim MM, Almalki WH, Nadeem MS, Sayyed N. Fustin Inhibits Oxidative Free Radicals and Inflammatory Cytokines in Cerebral Cortex and Hippocampus and Protects Cognitive Impairment in Streptozotocin-Induced Diabetic Rats. ACS Chem Neurosci 2021; 12:4587-4597. [PMID: 34860003 DOI: 10.1021/acschemneuro.1c00712] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The phytogenic flavanol component of the plant Rhus verniciflua Stokes is fustin which is implicated in various disease aliments and has promising therapeutic efficacy and a long history of its uses in the Indian medicinal system. The present study investigated the ameliorative effect of fustin in streptozotocin (STZ) induced cognitive impairments in the diabetic animal paradigm. A total of five different animal groups were used for the present study.The preclinical efficacy of fustin at 50 mg/kg and 100 mg/kg was studied in diabetic male rats by employing a 35-day study design. In the present investigation the Morris water maze test (MWM) and elevated plus maze (EPM) test were employed as behavioral paradigms for the assessment of memory impairments. The study design also carried out certain biochemical parameters which include glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT), malondialdehyde (MDA), nitric oxide (NO), relative interleukin-6 (IL-6), and IL-1B in samples obtained from cerebral cortex and hippocampus. The behavioral parameters with MWM and EPM were significant restored in fustin treatment groups as compared to elevated levels in the diabetic control group. Furthermore, fustin significantly improved the altered levels of several biochemical parameters for cognitive dysfunction such as GSH, SOD, CAT, MDA, NO, and relative IL-6 and IL-1B compared to a diabetic control group. The present investigation highlights certain preclinical pieces of evidence that strongly indicate that fustin might restore the normal cognitive function in the experimental animal paradigm.
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Affiliation(s)
- Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Nadeem Sayyed
- Clinical Research Department, Meril Life Sciences Pvt. Ltd., Vapi, Gujurat 396191, India
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13
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Alexander N, Alexander DC, Barkhof F, Denaxas S. Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning. BMC Med Inform Decis Mak 2021; 21:343. [PMID: 34879829 PMCID: PMC8653614 DOI: 10.1186/s12911-021-01693-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 11/15/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable. METHODS We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets. RESULTS We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters. CONCLUSION Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.
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Affiliation(s)
- Nonie Alexander
- Institute of Health Informatics, University College London, London, UK. .,Health Data Research UK, London, UK.
| | - Daniel C Alexander
- Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK
| | - Frederik Barkhof
- Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK.,UCL Institute of Neurology, University College London, London, UK.,Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Spiros Denaxas
- Institute of Health Informatics, University College London, London, UK.,Health Data Research UK, London, UK.,Alan Turing Institute, London, UK
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14
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Kao SL, Wang JH, Chen SC, Li YY, Yang YL, Lo RY. Impact of Comorbidity Burden on Cognitive Decline: A Prospective Cohort Study of Older Adults with Dementia. Dement Geriatr Cogn Disord 2021; 50:43-50. [PMID: 33789290 DOI: 10.1159/000514651] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 01/21/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION The lack of longitudinal data of comorbidity burden makes the association between comorbidity and cognitive decline inconclusive. We aimed to measure comorbidity and assess its effects on cognitive decline in mild to moderate dementia. METHODS This was a prospective cohort study. The participants were enrolled from the Hualien Tzu Chi Hospital between January 2015 and December 2018. We enrolled 175 older adults with mild to moderate dementia and conducted in-person interviews to follow-up comorbidity and cognitive function annually. The comorbidity burden indices included Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Charlson Comorbidity Index (CCI), and Medication Regimen Complexity Index (MRCI), and cognitive function was measured by Mini-Mental State Examination (MMSE) and clock drawing test. We employed the generalized estimating equations to assess the longitudinal effect of time-varying comorbidity burden on cognitive decline after adjusting for age, sex, and education. RESULTS Most patients were diagnosed with Alzheimer's disease (88.6%) and in the early stage of dementia (Clinical Dementia Rating [CDR] = 0.5, 57.1%; CDR = 1, 36.6%). Multimorbidity was common (median: 3), and the top 3 most common comorbidities were osteoarthritis (67.4%), hypertension (65.7%), and hyperlipidemia (36.6%). The severity index of CIRS-G was significantly associated with cognitive decline in MMSE after adjusting for age, sex, and education. CCI and MRCI scores were, however, not associated with cognitive function. CONCLUSION The severity index of CIRS-G outperforms CCI and MRCI in reflecting the longitudinal effect of comorbidity burden on cognitive decline in mild to moderate dementia.
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Affiliation(s)
- Sheng-Lun Kao
- Division of Geriatric Medicine, Department of Family Medicine, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Jen-Hung Wang
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Shu-Cin Chen
- Division of Cognitive and Geriatric Neurology, Department of Neurology, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yu-Ying Li
- Division of Cognitive and Geriatric Neurology, Department of Neurology, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Ya-Lin Yang
- Division of Cognitive and Geriatric Neurology, Department of Neurology, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Raymond Y Lo
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,Division of Cognitive and Geriatric Neurology, Department of Neurology, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
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15
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Garfield V, Farmaki AE, Fatemifar G, Eastwood SV, Mathur R, Rentsch CT, Denaxas S, Bhaskaran K, Smeeth L, Chaturvedi N. Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank. Diabetes 2021; 70:2313-2321. [PMID: 33632741 DOI: 10.2337/db20-0895] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 06/06/2021] [Indexed: 11/13/2022]
Abstract
We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank (n = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and diabetes and HbA1c We used conventional inverse-variance-weighted (IVW) MR alongside MR sensitivity analyses. Using IVW, genetic liability to type 2 diabetes was not associated with RT (exponentiated β [expβ] = 1.00 [95% CI 1.00; 1.00]), visual memory (expβ = 1.00 [95% CI 0.99; 1.00]), WMHV (expβ = 0.99 [95% CI 0.97; 1.01]), HV (β-coefficient mm3 = -2.30 [95% CI -12.39; 7.78]) or AD (odds ratio [OR] 1.15 [95% CI 0.87; 1.52]). HbA1c was not associated with RT (expβ = 1.00 [95% CI 0.99; 1.02]), visual memory (expβ = 0.99 [95% CI 0.96; 1.02]), WMHV (expβ = 1.03 [95% CI 0.88; 1.22]), HV (β = -21.31 [95% CI -82.96; 40.34]), or risk of AD (OR 1.09 [95% CI 0.42; 2.83]). IVW showed that reaction time was not associated with diabetes risk (OR 0.94 [95% CI 0.54; 1.65]), or with HbA1c (β-coefficient mmol/mol = -0.88 [95% CI = -1.88; 0.13]) after exclusion of a pleiotropic variant. Overall, we observed little evidence of causal association between genetic instruments for type 2 diabetes or peripheral glycemia and some measures of cognition and brain structure in midlife.
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Affiliation(s)
- Victoria Garfield
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, U.K.
| | - Aliki-Eleni Farmaki
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, U.K
| | - Ghazaleh Fatemifar
- Institute of Health Informatics, University College London, London, U.K
- Health Data Research UK, London, U.K
| | - Sophie V Eastwood
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, U.K
| | - Rohini Mathur
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, U.K
| | - Christopher T Rentsch
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, U.K
| | - Spiros Denaxas
- Institute of Health Informatics, University College London, London, U.K
- Health Data Research UK, London, U.K
- The Alan Turing Institute, British Library, London, U.K
| | - Krishnan Bhaskaran
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, U.K
| | - Liam Smeeth
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, U.K
| | - Nish Chaturvedi
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, U.K
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16
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Lotan R, Ganmore I, Livny A, Itzhaki N, Waserman M, Shelly S, Zacharia M, Moshier E, Uribarri J, Beisswenger P, Cai W, Troen AM, Beeri MS. Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial. J Alzheimers Dis 2021; 82:1785-1795. [PMID: 34250935 DOI: 10.3233/jad-210131] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. OBJECTIVE The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). METHODS The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. RESULTS At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. CONCLUSION The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.
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Affiliation(s)
- Roni Lotan
- The Nutrition and Brain Health Laboratory, The Institute of Biochemistry, Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Rehovot, Israel.,The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel
| | - Ithamar Ganmore
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel.,Memory Clinic, Sheba Medical Center, Tel Hashomer, Israel.,Neurology department, Sheba Medical Center, Tel Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Abigail Livny
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Division of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, Israel
| | - Nofar Itzhaki
- Division of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, Israel
| | - Mark Waserman
- Division of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, Israel
| | - Shahar Shelly
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel.,Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Moran Zacharia
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel
| | - Erin Moshier
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jaime Uribarri
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Weijing Cai
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Aron M Troen
- The Nutrition and Brain Health Laboratory, The Institute of Biochemistry, Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Michal Schnaider Beeri
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel.,Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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17
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Garfield V, Farmaki A, Eastwood SV, Mathur R, Rentsch CT, Bhaskaran K, Smeeth L, Chaturvedi N. HbA1c and brain health across the entire glycaemic spectrum. Diabetes Obes Metab 2021; 23:1140-1149. [PMID: 33464682 PMCID: PMC8261644 DOI: 10.1111/dom.14321] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/12/2021] [Accepted: 01/15/2021] [Indexed: 12/20/2022]
Abstract
AIM To understand the relationship between HbA1c and brain health across the entire glycaemic spectrum. MATERIALS AND METHODS We used data from the UK Biobank cohort consisting of 500,000 individuals aged 40-69 years. HbA1c and diabetes diagnosis were used to define baseline glycaemic categories. Our outcomes included incident all-cause dementia, vascular dementia (VD), Alzheimer's dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. The reference group was normoglycaemic individuals (HbA1c ≥35 & <42 mmol/mol). Our maximum analytical sample contained 449,973 individuals with complete data. RESULTS Prediabetes and known diabetes increased incident VD (HR 1.54; 95% CI = 1.04, 2.28 and HR 2.97; 95% CI = 2.26, 3.90, respectively). Known diabetes increased all-cause and AD risk (HR 1.91; 95% CI = 1.66, 2.21 and HR 1.84; 95% CI = 1.44, 2.36, respectively). Prediabetes and known diabetes elevated the risks of cognitive decline (OR 1.42; 1.48, 2.96 and OR 1.39; 1.04, 1.75, respectively). Prediabetes, undiagnosed and known diabetes conferred higher WMH volumes (3%, 22% and 7%, respectively) and lower HV (36, 80 and 82 mm3 , respectively), whereas low-normal HbA1c had 1% lower WMH volume and 12 mm3 greater HV. CONCLUSION Both prediabetes and known diabetes are harmful in terms of VD, cognitive decline and AD risks, as well as lower HV. Associations appeared to be somewhat driven by antihypertensive medication, which implies that certain cardiovascular drugs may ameliorate some of the excess risk. Low-normal HbA1c levels, however, are associated with more favourable brain health outcomes and warrant more in-depth investigation.
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Affiliation(s)
- Victoria Garfield
- MRC Unit for Lifelong Health and Ageing at UCLInstitute of Cardiovascular Science, University College LondonLondonUK
| | - Aliki‐Eleni Farmaki
- MRC Unit for Lifelong Health and Ageing at UCLInstitute of Cardiovascular Science, University College LondonLondonUK
| | - Sophie V. Eastwood
- MRC Unit for Lifelong Health and Ageing at UCLInstitute of Cardiovascular Science, University College LondonLondonUK
| | - Rohini Mathur
- Department of Non‐communicable Disease EpidemiologyLondon School of Hygiene & Tropical MedicineLondonUK
| | - Christopher T. Rentsch
- Department of Non‐communicable Disease EpidemiologyLondon School of Hygiene & Tropical MedicineLondonUK
| | - Krishnan Bhaskaran
- Department of Non‐communicable Disease EpidemiologyLondon School of Hygiene & Tropical MedicineLondonUK
| | - Liam Smeeth
- Department of Non‐communicable Disease EpidemiologyLondon School of Hygiene & Tropical MedicineLondonUK
| | - Nish Chaturvedi
- MRC Unit for Lifelong Health and Ageing at UCLInstitute of Cardiovascular Science, University College LondonLondonUK
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18
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Lotan R, Ganmore I, Livny A, Shelly S, Zacharia M, Uribarri J, Beisswenger P, Cai W, Schnaider Beeri M, Troen AM. Design and Feasibility of a Randomized Controlled Pilot Trial to Reduce Exposure and Cognitive Risk Associated With Advanced Glycation End Products in Older Adults With Type 2 Diabetes. Front Nutr 2021; 8:614149. [PMID: 33659267 PMCID: PMC7917071 DOI: 10.3389/fnut.2021.614149] [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: 10/05/2020] [Accepted: 01/04/2021] [Indexed: 01/08/2023] Open
Abstract
Introduction: Advanced glycation end products (AGEs) in diet and serum are positively correlated with chronic conditions such as type 2 diabetes and cognitive decline. Dietary reduction of AGEs was shown to reduce their level in serum and to have a beneficial effect on metabolic biomarkers. However, in part due to limitations of feasibility, clinical trials have not tested its effect on cognition in elderly. The current pilot study examines the feasibility of AGE reduction in elderly with diabetes in terms of recruitment and retention. Methods: The design is a randomized controlled pilot trial of dietary AGEs in elderly with type 2 diabetes (clinicaltrials.gov NCT02739971). Recruitment followed two stages: we first recruited participants with mild cognitive impairment (MCI), and after expanding inclusion criteria, we later recruited cognitively normal participants with subjective memory complaints (SMCs). Participants were randomized to two arms. Participants in the control arm received standard of care (SOC) guidelines for good glycemic control; those in the experimental arm, in addition to SOC guidelines, were instructed to lower their dietary AGE intake, primarily by changing their cooking methods. Participants were closely followed for dietary adherence over 6 months and evaluated before and after the intervention for adherence to the assigned diet, blood tests, cognitive performance, and brain MRI. Results: Seventy-five participants (52 with MCI and 23 cognitively normal with SMCs) were recruited primarily through mass mailing and advertising in social media websites. Seventy participants finished the study, and dropout was similar in both groups (7.5% in control vs. 5.7% in intervention, p = 0.757). The majority (57.5%) of participants in the AGEs-lowering arm showed very high adherence with the dietary guidelines. Discussion: Targeting feasible lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline. Observational evidence supports that AGEs may contribute to cognitive decline; however, the cognitive effect of reducing AGEs exposure has yet to be evaluated in a randomized controlled trial (RCT). The results of our pilot trial delineate a methodology including effective recruitment strategies, population of choice, and ways to assure high adherence during lifestyle modifications, and significantly advance progress toward a definitive and well-powered future RCT.
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Affiliation(s)
- Roni Lotan
- The Nutrition and Brain Health Laboratory, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Institute of Biochemistry, Food and Nutrition Science, The Hebrew University of Jerusalem, Rehovot, Israel.,The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
| | - Ithamar Ganmore
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.,Memory Clinic, Sheba Medical Center, Tel HaShomer, Israel.,Neurology Department, Sheba Medical Center, Tel HaShomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Abigail Livny
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Division of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
| | - Shahar Shelly
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.,Department of Neurology, Mayo Clinic, Rochester, MN, United States
| | - Moran Zacharia
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
| | - Jaime Uribarri
- Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | | | - Weijing Cai
- Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Michal Schnaider Beeri
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.,Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Aron M Troen
- The Nutrition and Brain Health Laboratory, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Institute of Biochemistry, Food and Nutrition Science, The Hebrew University of Jerusalem, Rehovot, Israel
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19
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Ganmore I, Elkayam I, Ravona-Springer R, Lin HM, Liu X, Plotnik M, Buchman AS, Berman Y, Schwartz J, Sano M, Heymann A, Beeri MS. Deterioration in Motor Function Over Time in Older Adults With Type 2 Diabetes is Associated with Accelerated Cognitive Decline. Endocr Pract 2021; 26:1143-1152. [PMID: 33471716 DOI: 10.4158/ep-2020-0289] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 06/07/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period. METHODS Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains' z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates. RESULTS Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition (P = .004), language/semantic categorization (P = .006) and episodic memory (P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition (P = .050), attention/working memory (P = .047) and language/semantic categorization (P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions (P = .025) and language/semantic categorization (P = .006). CONCLUSION In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D.
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Affiliation(s)
- Ithamar Ganmore
- From the Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
| | - Isak Elkayam
- the Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Ramit Ravona-Springer
- From the Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel; the Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Hung-Mo Lin
- the Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York
| | - Xiaoyu Liu
- the Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York
| | - Meir Plotnik
- the Center for Advanced Technologies in Rehabilitation, Sheba Medical Center, Israel
| | - Aron S Buchman
- the Rush Alzheimer's Disease Center, Rush University, Illinois
| | - Yuval Berman
- From the Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
| | - Jonathan Schwartz
- From the Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
| | - Mary Sano
- the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York
| | - Anthony Heymann
- the Sackler Faculty of Medicine, Tel Aviv University, Israel; the Maccabi Health Services, Israel
| | - Michal Schnaider Beeri
- From the Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
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20
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Tripathi R, Tripathi S, Pandey N, Srivastava A, Usman K, Ali W, Tiwari S. Cognitive status of older adults with diabetes mellitus, hypertension, and dyslipidemia on Hindi Cognitive Screening Test and Saint Louis University Mental State. JOURNAL OF GERIATRIC MENTAL HEALTH 2021. [DOI: 10.4103/jgmh.jgmh_43_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Guo M, Kang K, Wang A, Jia J, Zhang J, Wang Y, Wang D, Chen S, Zhao X. Association of diabetes status with cognitive impairment in two Chinese rural communities. J Neurol Sci 2020; 415:116894. [PMID: 32446011 DOI: 10.1016/j.jns.2020.116894] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 04/20/2020] [Accepted: 05/07/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND PURPOSE Diabetes may be one of the risk factors of cognitive impairment. In this study, we aimed to investigate the relationship between diabetes status and cognitive impairment among the middle-aged and elderly population (≥40 years) in Chinese rural communities. METHODS A sample of 3392 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Cognitive function was assessed by the Beijing edition of the Montreal cognitive assessment (MoCA) scale. Cognitive impairment was diagnosed as a MoCA score < 26. Diabetes status was divided into three groups------Normal: fasting plasma glucose (FPG) ≤ 5.5 mmol/L, Prediabetes: 5.6 ≤ FPG ≤ 6.9 mmol/L, Diabetes: FPG ≥ 7.0 mmol/L or with a history of diabetes. Multivariate logistic regression was used to analyze the association between diabetes status and cognitive impairment. RESULTS Out of the 3392 enrolled participants, 2023(59.6%) had cognitive impairment, 1586(46.8%) had abnormal fasting plasma glucose including 867(25.6%) prediabetes and 719(21.2%) diabetes. After adjusting for potential risk factors, we found prediabetes (OR: 1.22, 95%CI: 1.03-1.45) and diabetes (OR: 1.28, 95%CI: 1.06-1.55) are all associated with cognitive impairment, especially in the domains of language (prediabetes: OR: 1.14, 95%CI: 1.05-1.25; diabetes: OR:1.13, 95%CI: 1.03-1.24), visuospatial/executive functions (diabetes: OR: 1.50, 95%CI: 1.22-1.84) and attention (diabetes: OR: 1.15, 95%CI: 1.02-1.31). CONCLUSIONS In this large community-based study, we found diabetes status may be an independent risk factor for cognitive impairment, particularly in domains of language, visuospatial/executive functions, and attention.
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Affiliation(s)
- Mengyi Guo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Kaijiang Kang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jiaokun Jia
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jia Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yu Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Dandan Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Shengyun Chen
- Department of Neurology, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
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Jensen CS, Musaeus CS, Frikke-Schmidt R, Andersen BB, Beyer N, Gottrup H, Høgh P, Vestergaard K, Wermuth L, Frederiksen KS, Waldemar G, Hasselbalch S, Simonsen AH. Physical Exercise May Increase Plasma Concentration of High-Density Lipoprotein-Cholesterol in Patients With Alzheimer's Disease. Front Neurosci 2020; 14:532. [PMID: 32536853 PMCID: PMC7269030 DOI: 10.3389/fnins.2020.00532] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 04/29/2020] [Indexed: 12/27/2022] Open
Abstract
Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n = 90) or treatment as usual (n = 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.
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Affiliation(s)
- Camilla Steen Jensen
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Christian Sandøe Musaeus
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Ruth Frikke-Schmidt
- Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Birgitte Bo Andersen
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Nina Beyer
- Department of Physical and Occupational Therapy, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Hanne Gottrup
- Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Høgh
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Regional Dementia Research Centre, Department of Neurology, Zealand University Hospital, Roskilde, Denmark
| | | | - Lene Wermuth
- Dementia Clinic, Department of Neurology, Odense University Hospital, Odense, Denmark
| | | | - Gunhild Waldemar
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Steen Hasselbalch
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Anja Hviid Simonsen
- Danish Dementia Research Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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Association of Brain-Derived Neurotrophic Factor With Cognitive Function: An Investigation of Sex Differences in Patients With Type 2 Diabetes. Psychosom Med 2020; 81:488-494. [PMID: 31083054 DOI: 10.1097/psy.0000000000000709] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Although a reduction in brain-derived neurotrophic factor (BDNF) has been implicated as a cause of cognitive impairment in type 2 diabetes mellitus (T2DM), the role of sex in moderating this effect has not been explored. METHODS We compared the difference in serum BDNF and performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) between 96 men and 134 women with T2DM. We compared this with the difference in serum BDNF and performance in the control group (104 men, 144 women). RESULTS Patients with T2DM performed worse on most RBANS indices (η = 0.372, all p < .05); within T2DM patients, men performed worse than women on the delayed memory score (74.1 (12.1) versus 79.9 (11.5), p = .002) and on the total score (71.4 (11.5) versus 76.5 (10.8), p = .025). Serum BDNF was lower in patients with T2DM versus controls (7.5 (2.7) ng/ml versus 11.5 (2.7) ng/ml, p < .001), and in men compared with women (6.9 (2.4) versus 7.9 (2.8), p = .024). Serum BDNF levels positively correlated with delayed memory score in patients with T2DM (β = 0.19, p = .007). However, this association was only observed in women, not in men (pinteraction = 0.04). Among healthy controls, no sex differences were noted in either RBANS or BDNF levels (η = 0.04, Cohen's d < 0.163, all p > .05). CONCLUSIONS Our results show sex differences in poorer cognitive performance, lower BDNF concentration, and their relationship in T2DM patients, suggesting that female sex may be a protective factor for cognitive decline in T2DM patients. However, the findings should be regarded as preliminary because of the cross-sectional design and chronicity of the diabetes.
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Sharma G, Parihar A, Talaiya T, Dubey K, Porwal B, Parihar MS. Cognitive impairments in type 2 diabetes, risk factors and preventive strategies. J Basic Clin Physiol Pharmacol 2020; 31:/j/jbcpp.ahead-of-print/jbcpp-2019-0105/jbcpp-2019-0105.xml. [PMID: 31967962 DOI: 10.1515/jbcpp-2019-0105] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 10/25/2019] [Indexed: 06/10/2023]
Abstract
Mild cognitive impairment (MCI) is a modifiable risk factor in progression of several diseases including dementia and type 2 diabetes. If cognitive impairments are not reversed at an early stage of appearance of symptoms, then the prolonged pathogenesis can lead to dementia and Alzheimer's disease (AD). Therefore, it is necessary to detect the risk factors and mechanism of prevention of cognitive dysfunction at an early stage of disease. Poor lifestyle, age, hyperglycemia, hypercholesterolemia, and inflammation are some of the major risk factors that contribute to cognitive and memory impairments in diabetic patients. Mild cognitive impairment was seen in those individuals of type 2 diabetes, who are on an unhealthy diet. Physical inactivity, frequent alcohol consumptions, and use of packed food products that provides an excess of cheap calories are found associated with cognitive impairment and depression in diabetic patients. Omega fatty acids (FAs) and polyphenol-rich foods, especially flavonoids, can reduce the bad effects of an unhealthy lifestyle; therefore, the consumption of omega FAs and flavonoids may be beneficial in maintaining normal cognitive function. These functional foods may improve cognitive functions by targeting many enzymes and molecules in cells chiefly through their anti-inflammatory, antioxidant, or signaling actions. Here, we provide the current concepts on the risk factors of cognitive impairments in type 2 diabetes and the mechanism of prevention, using omega FAs and bioactive compounds obtained from fruits and vegetables. The knowledge derived from such studies may assist physicians in managing the health care of patients with cognitive difficulties.
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Affiliation(s)
- Garima Sharma
- School of Studies in Zoology and Biotechnology, Vikram University, Ujjain, MP, India
| | - Arti Parihar
- Department of Science, Bellingham Technical College, Bellingham, WA, USA
| | - Tanay Talaiya
- School of Studies in Zoology and Biotechnology, Vikram University, Ujjain, MP, India
| | - Kirti Dubey
- School of Studies in Zoology and Biotechnology, Vikram University, Ujjain, MP, India
| | - Bhagyesh Porwal
- School of Studies in Zoology and Biotechnology, Vikram University, Ujjain, MP, India
| | - Mordhwaj S Parihar
- School of Studies in Zoology and Biotechnology, Vikram University, Ujjain, MP, India, Phone: +91-734-2511317
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25
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Epidemiology of Alzheimer's Disease and Dementia in Arab Countries: A Systematic Review. Behav Neurol 2019; 2019:3935943. [PMID: 31772681 PMCID: PMC6854962 DOI: 10.1155/2019/3935943] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 05/25/2019] [Accepted: 09/16/2019] [Indexed: 11/17/2022] Open
Abstract
Background/Objectives Contrary to popular belief, the condition of dementia is not an actual discrete disease, but rather a group of symptoms, most notable of which is the disturbance of memory and social ability, often severe enough to impair daily functioning. As a result, it has been a major cause of functional deterioration among varying populations in the world. This study is aimed at reviewing the epidemiology of dementia in Arab countries in terms of its prevalence, distribution, and risk factors. Methods A systematic literature review was conducted using articles published in PubMed, Embase, Scopus, and other local journals between 1990 and 2018. After applying the inclusion and exclusion criteria, a total of 18 studies were concluded to be eligible for the review. Results Prevalence studies demonstrated that dementia is indeed a prevalent condition in Arab countries, ranging between 1.1% and 2.3% among age groups of 50 years and older, as well as between 13.5% and 18.5% among age groups of 80 years and above. However, these results are not different from those of many other countries in the world. Moreover, prevalence was found to vary depending on sociodemographic characteristics. Major risk factors of dementia included hypertension, low income, and low education, while the risk of developing dementia is increased by obesity, diabetes mellitus, and cardiovascular risk factors. Despite the growing evidence regarding the epidemiological distribution and determinants of dementia worldwide, studies from the Arab region remain scarce. Conclusion This systematic review highlights the need for population-based studies to provide necessary information for developing preventive and curative strategies specific to the Arab region.
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26
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Fried PJ, Pascual-Leone A, Bolo NR. Diabetes and the link between neuroplasticity and glutamate in the aging human motor cortex. Clin Neurophysiol 2019; 130:1502-1510. [PMID: 31295719 PMCID: PMC6684252 DOI: 10.1016/j.clinph.2019.04.721] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 03/15/2019] [Accepted: 04/22/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVES In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic metabolites with measures of cortical plasticity in older adults across the spectrum of glucose intolerance/insulin resistance. METHODS Forty adults (50-87 years: 17-T2DM, 14-pre-diabetes, 9-controls) underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2 cm3 region around the hand knob of the left primary motor cortex. Thirty-six also underwent a separate transcranial magnetic stimulation (TMS) assessment of cortical excitability and plasticity using single-pulse TMS and intermittent theta-burst stimulation targeting the same brain region. RESULTS Group differences were observed in relative concentrations of glutamine (p = .028), glucose (p = .008), total cholines (p = .048), and the glutamine/glutamate ratio (p = .024). Cortical plasticity was reduced in both T2DM and pre-diabetes groups relative to controls (p-values < .05). Only the T2DM group showed a significant positive association between glutamate concentration and plasticity (r = .56, p = .030). CONCLUSIONS Neuroplastic mechanisms are already impaired in pre-diabetes. In T2DM, reduced cortico-motor plasticity is associated with lower cortical glutamate concentration. SIGNIFICANCE Impaired plasticity in T2DM is associated with low glutamatergic metabolite levels. The glutamatergic neurotransmission system constitutes a potential therapeutic target for cognitive problems linked to plasticity-related deficiencies in T2DM.
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Affiliation(s)
- Peter J Fried
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
| | - Alvaro Pascual-Leone
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Institut Guttman, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain
| | - Nicolas R Bolo
- Spectroscopy, Psychiatry and Imaging Neuroscience Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
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27
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Hegde V, Vijayan M, Kumar S, Akheruzzaman M, Sawant N, Dhurandhar NV, Reddy PH. Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis. Biochim Biophys Acta Mol Basis Dis 2019; 1865:165531. [PMID: 31398466 DOI: 10.1016/j.bbadis.2019.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 07/30/2019] [Accepted: 08/05/2019] [Indexed: 12/18/2022]
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are unclear, several risk factors have been identified, including impaired glycemic control, which significantly increases the risk of cognitive decline and AD. In vitro and in vivo studies show that human adenovirus 36 (Ad36) improves glycemic control by increasing cellular glucose uptake in cells, experimental animal models and in humans who are naturally exposed to the virus. This study, tested improvement in glycemic control by Ad36 and delay in onset of cognitive decline in APPswe transgenic mice (Tg2576 line), a model of genetic predisposition to impaired glycemic control and AD. Three-month old APPswe mice were divided into Ad36 infected (Ad36) or mock infected (control) groups and baseline glycemic control measured by glucose tolerance test (GTT) prior to infection. Changes in glycemic control were determined 10- and 24-week post infection. Serum insulin was also measured during GTT. Cognition was determined by Y-maze test, while motor coordination and skill acquisition by rotarod test. Glycemic control as determined by GTT showed less deterioration in Ad36 infected mice over time, accompanied by a significant attenuation of cognitive decline. Analysis of brain tissue lysate showed significantly reduced levels of amyloid beta 42 in Ad36 mice relative to control mice. Golgi-Cox staining analysis also revealed reduced dendritic spines and synaptic gene expression in control mice compared to Ad36 infected mice. This proof of concept study shows that in a mouse model of AD, Ad36 improves glycemic control and ameliorates cognitive decline.
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Affiliation(s)
- V Hegde
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
| | - M Vijayan
- Internal Medicine, Cell Biology and Biochemistry, Neuroscience/Pharmacology and Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - S Kumar
- Internal Medicine, Cell Biology and Biochemistry, Neuroscience/Pharmacology and Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Md Akheruzzaman
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
| | - N Sawant
- Internal Medicine, Cell Biology and Biochemistry, Neuroscience/Pharmacology and Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - N V Dhurandhar
- Obesity and Metabolic Health Laboratory, Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
| | - P H Reddy
- Internal Medicine, Cell Biology and Biochemistry, Neuroscience/Pharmacology and Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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Irisin Attenuates Neuroinflammation and Prevents the Memory and Cognitive Deterioration in Streptozotocin-Induced Diabetic Mice. Mediators Inflamm 2019; 2019:1567179. [PMID: 31281225 PMCID: PMC6590589 DOI: 10.1155/2019/1567179] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 03/30/2019] [Accepted: 05/13/2019] [Indexed: 12/11/2022] Open
Abstract
Diabetes mellitus (DM) patients experience memory and cognitive deficits. The mechanisms underlying this dysfunction in the brain of DM patients are not fully understood, and therefore, no optimized therapeutic strategy has been established so far. The aim of the present study was to assess whether irisin was able to improve memory and cognitive performance in a streptozotocin-induced diabetic mouse model. A diabetic mouse model was established and behavioral tests were performed. We also set up primary cultures for mechanism studies. Western blots and EMSA were used for molecular studies. Significant impairment of cognition and memory was observed in these DM mice, which could be effectively prevented by irisin cotreatment. We also found upregulated levels of GFAP protein, reduced synaptic protein expression, and increased levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the brains; however, irisin significantly attenuated these cellular responses. Meanwhile, our results demonstrated that irisin inhibited the activation of P38, STAT3, and NFκB proteins of DM mice. Furthermore, our results suggested that irisin might regulate the function of P38, STAT3, and NFκB in hippocampal tissues of DM mice. Collectively, irisin inhibited neuroinflammation in STZ-induced DM mice by inhibiting cytokine release and improving their cognitive function. Our findings revealed the mechanism of irisin's anti-inflammatory effect in the CNS.
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Parahippocampal gyrus expression of endothelial and insulin receptor signaling pathway genes is modulated by Alzheimer's disease and normalized by treatment with anti-diabetic agents. PLoS One 2018; 13:e0206547. [PMID: 30383799 PMCID: PMC6211704 DOI: 10.1371/journal.pone.0206547] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 10/15/2018] [Indexed: 12/14/2022] Open
Abstract
A large body of literature links risk of cognitive decline, mild cognitive impairment (MCI) and dementia with Type 2 Diabetes (T2D) or pre-diabetes. Accumulating evidence implicates a close relationship between the brain insulin receptor signaling pathway (IRSP) and the accumulation of amyloid beta and hyperphosphorylated and conformationally abnormal tau. We showed previously that the neuropathological features of Alzheimer's disease (AD were reduced in patients with diabetes who were treated with insulin and oral antidiabetic medications. To understand better the neurobiological substrates of T2D and T2D medications in AD, we examined IRSP and endothelial cell markers in the parahippocampal gyrus of controls (N = 30), of persons with AD (N = 19), and of persons with AD and T2D, who, in turn, had been treated with anti-diabetic drugs (insulin and or oral agents; N = 34). We studied the gene expression of selected members of the IRSP and selective endothelial cell markers in bulk postmortem tissue from the parahippocampal gyrus and in endothelial cell enriched isolates from the same brain region. The results indicated that there are considerable abnormalities and reductions in gene expression (bulk tissue homogenates and endothelial cell isolates) in the parahippocampal gyri of persons with AD that map directly to genes associated with the microvasculature and the IRSP. Our results also showed that the numbers of abnormally expressed microvasculature and IRSP associated genes in diabetic AD donors who had been treated with anti-diabetic agents were reduced significantly. These findings suggest that anti-diabetic treatments may reduce or normalize compromised microvascular and IRSP functions in AD.
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30
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Rosa IM, Henriques AG, Carvalho L, Oliveira J, da Cruz E Silva OAB. Screening Younger Individuals in a Primary Care Setting Flags Putative Dementia Cases and Correlates Gastrointestinal Diseases with Poor Cognitive Performance. Dement Geriatr Cogn Disord 2018; 43:15-28. [PMID: 27907913 DOI: 10.1159/000452485] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/13/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Diagnosing dementia is challenging in many primary care settings, given the limited human resources and the lack of current diagnostic tools. With this in mind, a primary care-based cohort was established in the Aveiro district of Portugal. METHODS A total of 568 participants were evaluated using cognitive tests and APOE genotyping. RESULTS The findings revealed a dementia prevalence of 12%. A strong correlation between increasing Clinical Dementia Rating (CDR) scores and education was clearly evident. Other highly relevant risk factors were activities of daily living (ADL), instrumental ADL, aging, depression, gender, the APOE ε4 allele, and comorbidities (depression as well as gastrointestinal, osteoarticular, and neurodegenerative diseases). A hitherto unreported, significant correlation between gastrointestinal disease and high CDR score was clearly observable. CONCLUSIONS This study shows the merit of carrying out a dementia screening on younger subjects. Significantly, 71 subjects in the age group of 50-65 years were flagged for follow-up studies; furthermore, these cases with a potentially early onset of dementia were identified in a primary care setting.
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Affiliation(s)
- Ilka M Rosa
- Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal
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31
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Fried PJ, Schilberg L, Brem AK, Saxena S, Wong B, Cypess AM, Horton ES, Pascual-Leone A. Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits. J Alzheimers Dis 2018; 55:89-100. [PMID: 27636847 DOI: 10.3233/jad-160505] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. OBJECTIVE Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. METHODS A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. RESULTS In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. CONCLUSION Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions.
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Affiliation(s)
- Peter J Fried
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Lukas Schilberg
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Anna-Katharine Brem
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Department of Experimental Psychology, University of Oxford, Oxford, UK
| | - Sadhvi Saxena
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical School, Baltimore, MD, USA
| | - Bonnie Wong
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Frontotemporal Dementia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Aaron M Cypess
- Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.,Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Edward S Horton
- Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Alvaro Pascual-Leone
- Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Cognition, serum BDNF levels, and BDNF Val66Met polymorphism in type 2 diabetes patients and healthy controls. Oncotarget 2017; 9:3653-3662. [PMID: 29423073 PMCID: PMC5790490 DOI: 10.18632/oncotarget.23342] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 11/23/2017] [Indexed: 01/28/2023] Open
Abstract
Background and aims Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM. Results The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p < 0.01) except for the attention and visuospatial/constructional indexes (both p > 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls (p < 0.001), and BDNF was positively associated with delayed memory in patients (p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients (β = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score (β = –0.92, t = –3.40, p = 0.002) and language index (β = −1.17, t = –3.54, p = 0.001) among Val homozygote T2DM patients. Conclusions BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism. Methods We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.
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Palta P, Carlson MC, Crum RM, Colantuoni E, Sharrett AR, Yasar S, Nahin RL, DeKosky ST, Snitz B, Lopez O, Williamson JD, Furberg CD, Rapp SR, Golden SH. Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study. J Gerontol A Biol Sci Med Sci 2017; 73:123-130. [PMID: 28510619 PMCID: PMC5861864 DOI: 10.1093/gerona/glx076] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 05/05/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. METHODS Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. RESULTS Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. CONCLUSIONS Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia.
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Affiliation(s)
- Priya Palta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Department of Epidemiology, University of North Carolina at Chapel Hill
| | - Michelle C Carlson
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Rosa M Crum
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland
| | - Elizabeth Colantuoni
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - A Richey Sharrett
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland
| | - Sevil Yasar
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Richard L Nahin
- National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland
| | - Steven T DeKosky
- Department of Neurology, University of Florida College of Medicine, Gainesville
| | - Beth Snitz
- Department of Neurology, University of Pittsburgh, Pennsylvania
| | - Oscar Lopez
- Department of Neurology, University of Pittsburgh, Pennsylvania
| | - Jeff D Williamson
- Division of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Curt D Furberg
- Division of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Stephen R Rapp
- Division of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Sherita Hill Golden
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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de Oliveira MFB, Yassuda MS, Aprahamian I, Neri AL, Guariento ME. Hypertension, diabetes and obesity are associated with lower cognitive performance in community-dwelling elderly: Data from the FIBRA study. Dement Neuropsychol 2017; 11:398-405. [PMID: 29354220 PMCID: PMC5769998 DOI: 10.1590/1980-57642016dn11-040009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background Systemic hypertension (SH), diabetes mellitus (DM) and abdominal obesity may negatively impact cognitive performance. Objective To evaluate the association between SH, DM and abdominal obesity and cognitive performance among cognitively unimpaired elderly. Methods A cross-sectional study of individuals aged 65+ from seven Brazilian cities was conducted. SH and DM diagnoses were self-reported and abdominal circumference was objectively measured. Individuals who scored below the education-adjusted cutoff scores on the Mini-Mental State Examination (MMSE) were excluded. Results Among 2,593 elderly, 321 (12.38%) had SH, DM and abdominal obesity concomitantly (Group I) and 421 (16.23%) had none of the three diseases (Group II). Group I had a higher proportion of individuals that were women, aged 70-74 years, illiterate and with lower income. Group I had a higher number of participants with low cognitive performance (28.04% vs. 17.58% in Group II). Variables associated with poor cognitive performance were: female gender (OR: 2.43, p < 0.001); and lower education (OR: 0.410, p < 0.001). The presence of the three diseases and age were not significant in the education-adjusted model. Conclusion There was an association between cognition and the presence of SH, DM and obesity. However, education seems to be decisive in determining cognitive performance in the presence of these three conditions.
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Affiliation(s)
| | - Mônica Sanches Yassuda
- Post-Graduate Program in Gerontology - Faculty of Medical Sciences, State University of Campinas - Unicamp, Campinas, SP, Brazil.,School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil
| | - Ivan Aprahamian
- Department of Internal Medicine, Faculty of Medicine of Jundiaí, Jundiaí, SP, Brazil.,Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - Anita Liberalesso Neri
- Post-Graduate Program in Gerontology - Faculty of Medical Sciences, State University of Campinas - Unicamp, Campinas, SP, Brazil
| | - Maria Elena Guariento
- Post-Graduate Program in Gerontology - Faculty of Medical Sciences, State University of Campinas - Unicamp, Campinas, SP, Brazil
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Livny A, Ravona-Springer R, Heymann A, Priess R, Kushnir T, Tsarfaty G, Rabinov L, Moran R, Tik N, Moshier E, Cooper I, Greenbaum L, Silverman J, Levy A, Sano M, Bendlin BB, Buchman AS, Schnaider-Beeri M. Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes. Diabetes 2017; 66:2927-2932. [PMID: 28860127 PMCID: PMC5652603 DOI: 10.2337/db16-0987] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 08/23/2017] [Indexed: 01/28/2023]
Abstract
Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levels among Hp 1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.
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Affiliation(s)
- Abigail Livny
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
| | - Ramit Ravona-Springer
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- Memory Clinic, Sheba Medical Center, Tel HaShomer, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Anthony Heymann
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Maccabi Healthcare Services, Tel Aviv, Israel
| | | | - Tammar Kushnir
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Galia Tsarfaty
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Leeron Rabinov
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
| | - Reut Moran
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
| | - Niv Tik
- Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel
| | - Erin Moshier
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Itzik Cooper
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- Interdisciplinary Center Herzliya, Baruch Ivcher School of Psychology, Herzliya, Israel
| | - Lior Greenbaum
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel HaShomer, Israel
| | - Jeremy Silverman
- Icahn School of Medicine at Mount Sinai, New York, NY
- James J. Peters VA Medical Center, Bronx, NY
| | - Andrew Levy
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Mary Sano
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Aron S Buchman
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
| | - Michal Schnaider-Beeri
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel
- Icahn School of Medicine at Mount Sinai, New York, NY
- Interdisciplinary Center Herzliya, Baruch Ivcher School of Psychology, Herzliya, Israel
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Barocco F, Spallazzi M, Concari L, Gardini S, Pelosi A, Caffarra P. The Progression of Alzheimer's Disease: Are Fast Decliners Really Fast? A Four-Year Follow-Up. J Alzheimers Dis 2017; 57:775-786. [PMID: 28304306 PMCID: PMC5389047 DOI: 10.3233/jad-161264] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background: The rate of cognitive and functional decline in Alzheimer’s disease (AD) changes across individuals. Objectives: Our purpose was to assess whether the concept of “fast decline” really fits its definition and whether cognitive and functional variables at onset can predict the progression of AD. Methods: 324 AD patients were included. We retrospectively examined their Mini-Mental State Examination (MMSE) total score and sub-items, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) at baseline and every six months for a 4-year follow-up. Patients were divided into “fast decliners” (n = 62), defined by a loss ≥5 points on the MMSE score within the first year from the baseline; “intermediate decliners” (n = 37), by a loss ≥5 points after the first year and before the 18th month; or “slow decliners” (n = 225), composed of the remaining patients. Results: At baseline, the groups did not differ on demographic, clinical, and cognitive variables. The decline at the end of the 4-year follow-up period seems to be similar among the different decline clusters. Predictors of disease progression have not been identified; only the MMSE total score at 12 months <14/30 was indicative of a poor prognosis. Conclusions: Even with the limitation due to the small sample size, the lack of differences in the disease progression in time in the different clusters suggest the inconsistency of the so-called “fast decliners”. This study was unable to show any significant difference among clusters of AD progression within a 4-year time interval. Further studies should better clarify whether a more consistent distinction exists between slow and fast decliners.
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Affiliation(s)
- Federica Barocco
- Section of Neurology, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Marco Spallazzi
- Section of Neurology, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | | | - Annalisa Pelosi
- Section of Psychology, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Paolo Caffarra
- Section of Neurology, Department of Medicine and Surgery, University of Parma, Parma, Italy
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Reitz C, Guzman VA, Narkhede A, DeCarli C, Brickman AM, Luchsinger JA. Relation of Dysglycemia to Structural Brain Changes in a Multiethnic Elderly Cohort. J Am Geriatr Soc 2017; 65:277-285. [PMID: 27917464 PMCID: PMC5311018 DOI: 10.1111/jgs.14551] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Abnormally high glucose levels (dysglycemia) increase with age. Epidemiological studies suggest that dysglycemia is a risk factor for cognitive impairment but the underlying pathophysiological mechanisms remain unclear. The objective of this study was to examine the relation of dysglycemia clinical categories (normal glucose tolerance (NGT), pre-diabetes, undiagnosed diabetes, known diabetes) with brain structure in older adults. We also assessed the relation between dysglycemia and cognitive performance. DESIGN Cross-sectional and longitudinal cohort study. SETTING Northern Manhattan (Washington Heights, Hamilton Heights, and Inwood). PARTICIPANTS Medicare recipients 65 years and older. MEASUREMENTS Dysglycemia categories were based on HBA1c or history of type 2 diabetes (diabetes). Brain structure (brain infarcts, white matter hyperintensities (WMH) volume, total gray matter volume, total white matter volume, total hippocampus volume) was assessed with brain magnetic resonance imaging; cognitive function (memory, language and visuospatial function, speed) was assessed with a validated neuropsychological battery. RESULTS Dysglycemia, defined with HbA1c as a continuous variable or categorically as pre-diabetes and diabetes, was associated with a higher number of brain infarcts, WMH volume and decreased total white matter, gray matter and hippocampus volumes cross-sectionally, and a significant decline in gray matter volume longitudinally. Dysglycemia was also associated with lower performance in language, speed and visuospatial function although these associations were attenuated when adjusted for education, APOE-ε4, ethnic group and vascular risk factors. CONCLUSION Our results suggest that dysglycemia affects brain structure and cognition even in elderly survivors, evidenced by higher cerebrovascular disease, lower white and gray matter volume, and worse language and visuospatial function and cognitive speed.
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Affiliation(s)
- Christiane Reitz
- Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY
- Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
| | - Vanessa A. Guzman
- Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY
| | - Atul Narkhede
- Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY
| | - Charles DeCarli
- Department of Neurology, Center for Neuroscience, University of California at Davis, Sacramento
- Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California at Davis, Sacramento
| | - Adam M. Brickman
- Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY
- Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY
| | - José A. Luchsinger
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
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Saedi E, Gheini MR, Faiz F, Arami MA. Diabetes mellitus and cognitive impairments. World J Diabetes 2016; 7:412-422. [PMID: 27660698 PMCID: PMC5027005 DOI: 10.4239/wjd.v7.i17.412] [Citation(s) in RCA: 134] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 07/23/2016] [Accepted: 08/08/2016] [Indexed: 02/05/2023] Open
Abstract
There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.
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Espeland MA, Erickson K, Neiberg RH, Jakicic JM, Wadden TA, Wing RR, Desiderio L, Erus G, Hsieh MK, Davatzikos C, Maschak-Carey BJ, Laurienti PJ, Demos-McDermott K, Bryan RN. Brain and White Matter Hyperintensity Volumes After 10 Years of Random Assignment to Lifestyle Intervention. Diabetes Care 2016; 39:764-71. [PMID: 27208378 PMCID: PMC4839171 DOI: 10.2337/dc15-2230] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 01/29/2016] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Type 2 diabetes increases the accumulation of brain white matter hyperintensities and loss of brain tissue. Behavioral interventions to promote weight loss through dietary changes and increased physical activity may delay these adverse consequences. We assessed whether participation in a successful 10-year lifestyle intervention was associated with better profiles of brain structure. RESEARCH DESIGN AND METHODS At enrollment in the Action for Health in Diabetes clinical trial, participants had type 2 diabetes, were overweight or obese, and were aged 45-76 years. They were randomly assigned to receive 10 years of lifestyle intervention, which included group and individual counseling, or to a control group receiving diabetes support and education through group sessions on diet, physical activity, and social support. Following this intervention, 319 participants from three sites underwent standardized structural brain magnetic resonance imaging and tests of cognitive function 10-12 years after randomization. RESULTS Total brain and hippocampus volumes were similar between intervention groups. The mean (SE) white matter hyperintensity volume was 28% lower among lifestyle intervention participants compared with those receiving diabetes support and education: 1.59 (1.11) vs. 2.21 (1.11) cc (P = 0.02). The mean ventricle volume was 9% lower: 28.93 (1.03) vs. 31.72 (1.03) cc (P = 0.04). Assignment to lifestyle intervention was not associated with consistent differences in cognitive function compared with diabetes support and education. CONCLUSIONS Long-term weight loss intervention may reduce the adverse impact of diabetes on brain structure. Determining whether this eventually delays cognitive decline and impairment requires further research.
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Affiliation(s)
- Mark A Espeland
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Kirk Erickson
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA
| | - Rebecca H Neiberg
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - John M Jakicic
- Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA
| | | | | | | | - Guray Erus
- University of Pennsylvania, Philadelphia, PA
| | | | | | | | - Paul J Laurienti
- Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC
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Jensen CS, Hasselbalch SG, Waldemar G, Simonsen AH. Biochemical Markers of Physical Exercise on Mild Cognitive Impairment and Dementia: Systematic Review and Perspectives. Front Neurol 2015; 6:187. [PMID: 26379621 PMCID: PMC4549649 DOI: 10.3389/fneur.2015.00187] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 08/12/2015] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The cognitive effects of physical exercise in patients with dementia disorders or mild cognitive impairment have been examined in various studies; however the biochemical effects of exercise from intervention studies are largely unknown. The objective of this systematic review is to investigate the published results on biomarkers in physical exercise intervention studies in patients with MCI or dementia. METHODS The PubMed database was searched for studies from 1976 to February 2015. We included intervention studies investigating the effect of physical exercise activity on biomarkers in patients with MCI or dementia. RESULTS A total of eight studies were identified (n = 447 patients) evaluating exercise regimes with variable duration (single session-three sessions/week for 26 weeks) and intensity (light-resistance training-high-intensity aerobic exercise). Various biomarkers were measured before and after intervention. Seven of the eight studies found a significant effect on their selected biomarkers with a positive effect of exercise on brain-derived neurotrophic factor, cholesterol, testosterone, estradiol, dehydroepiadrosterone, and insulin in the intervention groups compared with controls. CONCLUSION Although few studies suggest a beneficial effect on selected biomarkers, we need more knowledge of the biochemical effect of physical exercise in dementia or MCI.
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Affiliation(s)
- Camilla Steen Jensen
- Department of Neurology, Danish Dementia Research Centre, Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
| | - Steen Gregers Hasselbalch
- Department of Neurology, Danish Dementia Research Centre, Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Gunhild Waldemar
- Department of Neurology, Danish Dementia Research Centre, Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Anja Hviid Simonsen
- Department of Neurology, Danish Dementia Research Centre, Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
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Wu Q, Tchetgen Tchetgen EJ, Osypuk T, Weuve J, White K, Mujahid M, Glymour MM. Estimating the cognitive effects of prevalent diabetes, recent onset diabetes, and the duration of diabetes among older adults. Dement Geriatr Cogn Disord 2015; 39:239-49. [PMID: 25613323 DOI: 10.1159/000368654] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Little evidence is available on the effects of incident diabetes or diabetes duration on cognitive aging. METHODS We evaluated the effects of prevalent and incident diabetes on deteriorations in cognitive function, based on participants (n = 8,671) aged 65+ in the Health and Retirement Study in 2000. Inverse probability weighting was used to account for selective attrition and time-varying confounding of incident diabetes. RESULTS Prevalent diabetes predicted higher odds of dementia [odds ratio 1.27; 95% confidence interval (CI) 1.03-1.58] and worse memory (-0.06 in z-score units; 95% CI -0.10 to -0.02), but incident diabetes or diabetes duration up to 8 years of follow-up was not predictive. CONCLUSION Prevalent diabetes predicted lower cognition but not recent onset diabetes.
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Affiliation(s)
- Qiong Wu
- Institute of Social Science Survey, Peking University, Beijing, China
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The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics. Alzheimers Dement 2014; 10:769-78. [PMID: 25150735 DOI: 10.1016/j.jalz.2014.06.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/01/2014] [Accepted: 06/05/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND Type 2 diabetes (T2D) is associated with increased risk of dementia. The prospective longitudinal Israel Diabetes and Cognitive Decline study aims at identifying T2D-related characteristics associated with cognitive decline. METHODS Subjects are population-based T2D 65+, initially cognitively intact. Medical conditions, blood examinations, and medication use data are since 1998; cognitive, functional, demographic, psychiatric, DNA, and inflammatory marker study assessments were conducted every 18 months. Because the duration of T2D reflects its chronicity and implications, we compared short (0-4.99 years), moderate (5-9.99), and long (10+) duration for the first 897 subjects. RESULTS The long duration group used more T2D medications, had higher glucose, lower glomerular filtration rate, slower walking speed, and poorer cognitive functioning. Duration was not associated with most medical, blood, urine, and vital characteristics. CONCLUSIONS Tracking cognition, with face-to-face evaluations, exploiting 15 years of historical detailed computerized, easily accessible, and validated T2D-related characteristics may provide novel insights into T2D-related dementia.
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Yun HS, Kim E, Suh SR, Kim MH, Kim H. Diabetes reduces the cognitive function with the decrease of the visual perception and visual motor integration in male older adults. J Exerc Rehabil 2013; 9:470-6. [PMID: 24282807 PMCID: PMC3836550 DOI: 10.12965/jer.130059] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Revised: 09/06/2013] [Accepted: 10/04/2013] [Indexed: 01/21/2023] Open
Abstract
This study investigated the influence of diabetes on cognitive decline between the diabetes and non- diabetes patients and identified the associations between diabetes and cognitive function, visual perception (VP), and visual motor integration (VMI). Sixty elderly men (67.10± 1.65 yr) with and without diabetes (n= 30 in each group) who were surveyed by interview and questionnaire in South Korea were enrolled in this study. The score of Mini-Mental State Examination of Korean version (MMSE-KC), Motor-free Visual Perception Test-Vertical Format (MVPT-V), and Visual-Motor Integration 3rd Revision (VMI-3R) were assessed in all of the participants to evaluate cognitive function, VP, and VMI in each. The score of MMSE-KC in the diabetic group was significantly lower than that of the non-diabetes group (P< 0.01). Participants in the diabetes group also had lower MVPT-V and VMI-3R scores than those in the non-diabetes group (P< 0.01, respectively). Especially, the scores of figure-ground and visual memory among the subcategories of MVPT-V were significantly lower in the diabetes group than in the non-diabetes group (P< 0.01). These findings indicate that the decline in cognitive function in individuals with diabetes may be greater than that in non-diabetics. In addition, the cognitive decline in older adults with diabetes might be associated with the decrease of VP and VMI. In conclusion, we propose that VP and VMI will be helpful to monitor the change of cognitive function in older adults with diabetes as part of the routine management of diabetes-induced cognitive declines.
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Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, Woodward M, Boundy K, Ellis KA, Bush AI, Faux NG, Martins R, Szoeke C, Rowe C, Watters DA. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 2013; 36:2981-7. [PMID: 24009301 PMCID: PMC3781568 DOI: 10.2337/dc13-0229] [Citation(s) in RCA: 264] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODS Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22). RESULTS Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONS Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
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The influence of vascular risk factors on cognitive decline in patients with dementia: A systematic review. Maturitas 2013; 76:113-7. [DOI: 10.1016/j.maturitas.2013.06.011] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 06/07/2013] [Accepted: 06/14/2013] [Indexed: 11/22/2022]
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Kravitz E, Schmeidler J, Beeri MS. Type 2 diabetes and cognitive compromise: potential roles of diabetes-related therapies. Endocrinol Metab Clin North Am 2013; 42:489-501. [PMID: 24011882 PMCID: PMC3767929 DOI: 10.1016/j.ecl.2013.05.009] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes, like dementia, disproportionately affects the elderly. Diabetes has consistently been associated with risk of dementia, mild cognitive impairment, and cognitive decline suggesting that cognitive compromise is a deleterious manifestation of diabetes. This review summarizes observational studies and clinical trials of diabetes medications and their respective associations and effects on cognitive outcomes. Despite biological plausibility, results from most human clinical trials have failed to show any efficacy in treating Alzheimer disease symptomatology and pathology. Clinical trials targeting vascular-related outcomes, diabetic patients, or cognitively normal elderly at risk for dementia, may provide greater cognitive benefits.
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Affiliation(s)
- Efrat Kravitz
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
| | - James Schmeidler
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY
| | - Michal Schnaider Beeri
- The Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY
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Ravona-Springer R, Moshier E, Schmeidler J, Godbold J, Akrivos J, Rapp M, Grossman HT, Wysocki M, Silverman JM, Haroutunian V, Beeri MS. Changes in glycemic control are associated with changes in cognition in non-diabetic elderly. J Alzheimers Dis 2012; 30:299-309. [PMID: 22426020 DOI: 10.3233/jad-2012-120106] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The aim of the present study was to examine the relationship of changes in long term glucose levels as measured by Hemoglobin A1c (HbA1c) with simultaneous changes in cognition. The sample included in the present analysis consisted of 101 community dwelling non-diabetic elderly subjects participating in ongoing longitudinal studies of cognition. Subjects were included in this study if they were cognitively normal at baseline, had at least one co-temporaneous follow-up assessment of HbA1c and the Mini Mental State Exam (MMSE), and complete data on age, gender, race, and years of education. MMSE decline over time was the main outcome measure. In TOBIT mixed regression models, MMSE was the dependent variable and HbA1c the time-varying covariate. Sociodemographic (age, gender, and education), cardiovascular (hypertension and APOE4 status), and lifestyle (smoking and physical activity) covariates were included in the statistical model. After adjusting for age at follow-up, there was a decrease of 1.37 points in the MMSE (p = 0.0002) per unit increase in HbA1c. This result remained essentially unchanged after adjusting also for gender and education (p = 0.0005), cardiovascular factors (p = 0.0003), and lifestyle (p = 0.0006). Additionally, results remained very similar after excluding subjects with potentially incipient diabetes with HbA1c between 6 and 7. These findings suggest that in non-diabetic non-demented elderly subjects, an increase in HbA1c over time is associated with cognitive decline. Such results may have broad clinical applicability since manipulation of glucose control, even in non-diabetics, may affect cognitive performance, perhaps enabling preventive measures against dementia.
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Morley JE. Diabetes Mellitus: “The Times They Are A-Changin”. J Am Med Dir Assoc 2012; 13:574-5. [DOI: 10.1016/j.jamda.2012.06.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Accepted: 06/08/2012] [Indexed: 12/27/2022]
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Ravona-Springer R, Schnaider-Beeri M. The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Rev Neurother 2012; 11:1609-17. [PMID: 22014139 DOI: 10.1586/ern.11.152] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Diabetes and prediabetic states have consistently been shown to be risk factors for cognitive decline, mild cognitive impairment and dementia. The importance of these findings is that diabetes and diabetes-related factors are modifiable, potentially permitting interventions aimed at postponing or preventing dementia. However, diabetes control cannot yet be implemented universally in diabetic subjects as a strategy for dementia prevention since the mechanisms by which diabetes impairs brain function and cognition are not fully understood. It is not clear which of the diabetes-related factors is crucial to this relationship. In addition, strict diabetic control has been demonstrated to carry risk for certain diabetic populations. The aim of the current article is to discuss current understanding of the relationships of diabetes and some of its characteristics with dementia, and suggest future questions to be answered.
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Ravona-Springer R, Luo X, Schmeidler J, Wysocki M, Lesser GT, Rapp MA, Dahlman K, Grossman HT, Haroutunian V, Beeri MS. The association of age with rate of cognitive decline in elderly individuals residing in supporting care facilities. Alzheimer Dis Assoc Disord 2011; 25:312-6. [PMID: 21572311 PMCID: PMC3268208 DOI: 10.1097/wad.0b013e31820d880e] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES This study examines the effect of age on rate of cognitive decline in different stages of dementia, of nursing home and assisted-living residents. METHODS In this longitudinal study, the Mini Mental State Examination (MMSE) was used to measure rate of cognitive decline in subjects who were nondemented [Clinical Dementia Rating (CDR)=0; n=353], questionably demented (CDR=0.5; n=121), or frankly demented (CDR≥1; n=213) at baseline. RESULTS A generalized estimating equation was used to model the MMSE scores over time (mean follow-up 2.9±2.0 y). The generalized estimating equation model had the MMSE scores at successive follow-up time points as dependent variables and had linear and quadratic age, follow-up time from baseline, CDR at baseline, and all the interactions among them as independent variables, controlling for MMSE at baseline, sex, race, and education. The mean age of the entire sample was 85.2±7.4 years at baseline. There were no significant interactions of linear age effects with rate of cognitive decline. The analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships: in the nondemented group, there was no substantial quadratic association of age with the rate of cognitive decline (P=0.13); in the questionable demented group, the oldest subjects declined relatively faster (P=0.02); and in the demented group, the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages (P=0.07). CONCLUSIONS This study adds an additional aspect to the complexity of the association between age and rate of cognitive decline, showing that the direction and amplitude of this effect differs according to the stage along the course of cognitive decline.
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