Metformin in the Prevention of Alzheimer's Disease and Alzheimer's Disease Related Dementias

Abstract

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 AD related disorders (ADRD). This review seeks to summarize findings from human and non-human studies examining the association of metformin with AD/ADRD related outcomes. Studies in animal models suggest that metformin could decrease the risk of AD/ADRD through multiple mechanisms including neuroprotective effects, decreasing neuroinflammation, and decreasing AD pathology. However, there are non-human studies that suggest that metformin could increase the risk of AD/ADRD. Observational human studies are also 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.

Keywords: Alzheimer; Metformin; dementia; diabetes.