Metformin-use is associated with slowed cognitive decline and reduced incident dementia in older adults with type 2 diabetes mellitus: the Sydney Memory and Ageing Study

<b>Objective:</b> Type 2 diabetes mellitus (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin-use with incident dementia and cognitive decline over 6 years in diabetes, compared to those not receiving metformin and those without diabetes. <p><b>Research</b> <b>Design and Methods</b>: Prospective observational study of N=1037 non-demented community-dwelling older participants aged 70-90 at baseline (the Sydney Memory and Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease or progressive malignancy. Neuropsychological testing measured cognitive function every two years; a battery of tests measured executive function, memory, attention/speed, language and visuospatial function individually and to a construct of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal and parahippocampal volumes were measured by magnetic resonance at baseline and 2 years (n=526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, hypertension, stroke, smoking and apolipoprotein Ee4 carriage. </p> <p><b>Results</b>: Of n=1037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared to DM-noM. Incident dementia was significantly higher in DM-noMF compared to DM+MF (OR 5.29, 95%CI 1.17-23.88, p=0.05).</p> <p><b>Conclusions</b>: Older people with diabetes receiving metformin have slower cognitive decline and lower dementia risk. Large randomized studies in people with and without diabetes will determine whether these associations can be attributed to metformin. </p>