Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study.

Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer's disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case-control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002-2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23-1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02-4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.

The Relationship between Physical Exercise and Cognitive Function in Korean Middle Aged and Elderly Adults without Dementia.

This study investigated the association between physical exercise and cognitive function in Koreans aged 45 years or above without dementia. Data from the 2006 to 2018 Korean Longitudinal Study of Aging (KLoSA) were used. The general characteristics of the study population were investigated using analysis of variance (ANOVA). The association between total exercise time per week and cognitive function, measured based on the Mini-Mental State Examination (MMSE) scores, was investigated using the generalized estimating equation (GEE) model. Subgroup analysis was conducted based on age, educational level, and marital status. A total of 8888 participants were investigated, of which 5173 (58.2%) individuals did not exercise regularly. Among participants who did exercise, 676 (7.6%) individuals were categorized into the Q1, 1157 (13.0%) into the Q2, 908 (10.2%) into the Q3, and 974 (11.0%) into the Q4 group. The mean MMSE score was 26.81 ± 3.17. Compared to the 'no' exercise group, better MMSE scores were found in the Q1 (ß: 0.3523, p ≤ 0.0001), the Q2 (ß: 0.2011, p ≤ 0.0001), the Q3 (ß: 0.4075, p ≤ 0.0001), and the Q4 groups (ß: 0.3144, p ≤ 0.0001) after adjustment. The magnitude of this association was stronger in participants aged 65 years or above and in single or separated individuals. The findings of this study confirm a positive association between physical exercise and MMSE scores in the middle aged and elderly.