Metformin, age-related cognitive decline, and brain pathology.

The objective of this study was to evaluate the relation of metformin with change in cognition and brain pathology. During a mean of 8 years (SD = 5.5) of annual follow-up visits, 262/3029 participants were using metformin at any time during the study. Using a linear-mixed effect model adjusted for age, sex, and education, metformin users had slower decline on a score of global cognition compared to non-users (estimate = 0.017, SE = 0.007, p = 0.027). Analyses of cognitive domains showed a slower decline in episodic memory and semantic memory specifically. In sensitivity analysis, when examining any diabetes medication use vs none, no association was observed of any diabetes medication use with cognitive function. In the autopsy subset of 1584 participants, there was no difference in the level of Alzheimer's disease (AD) pathology or the presence of infarcts (of any size or location) between groups of metformin users vs non-users. However, in additional analyses, metformin users had higher odds of subcortical infarcts, and lower odds of atherosclerosis and arteriosclerosis.

Diabetes and function in different cognitive systems in older individuals without dementia.

OBJECTIVE: To examine the relation of type 2 diabetes to the level of function in five different cognitive systems in older individuals without dementia. RESEARCH DESIGN AND METHODS: Participants were 882 older men and women without dementia participating in the Rush Memory and Aging Project, a longitudinal clinical-pathological study of aging and dementia. They underwent uniform evaluations, which included clinical classification of dementia, and detailed cognitive function testing from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability, and global cognition were derived. Diabetes was identified by history and direct medication inspection. RESULTS: Diabetes was present in 116 (13%) participants. In separate linear regression models controlling for age, sex, and education, diabetes was associated with lower levels of semantic memory (P < 0.001) and perceptual speed (P = 0.005), but not with episodic memory, working memory, or visuospatial ability or with a measure of global cognition. The associations of diabetes with cognition were reduced when controlling for several vascular variables, and the associations were substantially stronger in current smokers than in individuals who never smoked or formerly smoked. CONCLUSIONS: These results suggest that type 2 diabetes is associated with cognitive impairment, especially in semantic memory and perceptual speed and that these effects may be modified by smoking status.