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Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?
Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry
Article type: Review Article
Authors: Tahmi, Mounaa | Benitez, Richardb | Luchsinger, José A.b; c; *
Affiliations: [a] Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY, USA | [b] Departments of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA | [c] Department of Epidemiology, Joseph P. Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA
Correspondence: [*] Correspondence to: José A. Luchsinger, MD MPH, Columbia University Irving Medical Center, 622 West 168th Street, PH9 Center room 210, New York, NY 10032, USA. Tel.: +1 212 305 4730; Fax: +1 212 305 9349; E-mail: jal94@cumc.columbia.edu.
Abstract: Background:Metformin is a safe and effective medication for type 2 diabetes (T2D) that has been proposed to decrease the risk of aging related disorders including Alzheimer’s disease (AD) and Alzheimer’s disease related disorders(ADRD). Objective:This review seeks to summarize findings from studies examining the association of metformin with AD/ADRD related outcomes. Methods:This is a narrative review of human studies, including observational studies and clinical trials, examining the association of metformin with cognitive and brain outcomes. We used PubMed as the main database for our literature search with a focus on English language human studies including observational studies and clinical trials. We prioritized studies published from 2013 until February 15, 2024. Results:Observational human studies are conflicting, but those with better study designs suggest that metformin use in persons with T2D is associated with a lower risk of dementia. However, these observational studies are limited by the use of administrative data to ascertain metformin use and/or cognitive outcomes. There are few clinical trials in persons without T2D that have small sample sizes and short durations but suggest that metformin could prevent AD/ADRD. There are ongoing studies including large clinical trials with long duration that are testing the effect of metformin on AD/ADRD outcomes in persons without T2D at risk for dementia. Conclusions:Clinical trial results are needed to establish the effect of metformin on the risk of AD and ADRD.
Keywords: Alzheimer’s disease, dementia, diabetes, metformin
DOI: 10.3233/JAD-240495
Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S345-S356, 2024
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