Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study

Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system–penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers. Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were randomized to receive metformin then placebo for 8 weeks each or vice versa. CSF and neuroimaging (Arterial Spin Label MRI) data were collected for biomarker analyses, and cognitive testing was performed. Metformin was…

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