Effect of metformin on changes in cognitive function in patients with diabetes

Abstract

Introduction: Diabetes mellitus (DM) is a chronic disease that has high morbidity and mortality related to cardiovascular complications and microvascular disease, especially in the elderly. In addition, DM is known to increase the risk of Alzheimers dementia by two to three times. Therefore it is important to inhibit its development and progression during the management of DM. However, there is a concern that metformin which is widely used as the first line antidiabetic medication is associated with a decrease in cognitive function. The aim of the present study is to investigate the associations between metformin use and cognitive impairment in patients with diabetes.

Methods: As an observational study, over 5457 patients registered with the Department of Mental Health of Boramae Medical center (BMC) and the Dementia Project from 2011 could be evaluated. We reviewed the medical records of patients and compared baseline characteristics according to DM and non-DM, and divided the DM groups into metformin user and nonuser groups then compared their cognitive function using mainly the Mini-Mental state Examination-KC (MMSE-KC), the Korean version of the Consortium to Establish a Registry for Alzheimers Diseases Assessment (CERAD-K), activities of daily living (ADL) skills and Short form of the Geriatric Depression Scale (SGDS). Subjects performed the tests at baseline and at one- or two- year follow-up periods. Results: Among the 2208 individuals who participated in this study, 608 had diabetes mellitus, and 34.7% (n=211) of the DM group used metformin at baseline. The mean age of metformin users was 73.8 years, and 38% were male. Patients with metformin were younger (73.8±7.5 vs. 75.5±7.9 years, p-value 0.01), had higher HbA1c levels, lower HDL – C levels, lower LDL – C levels, and lower AST levels, all showing statistical significance. There were no significant differences in cognitive dysfunction as assessed by MMSE-KC, CERAD, and ADL between metformin users and nonusers after adjusting for age, sex, education-year, HbA1c levels, and LDL levels. In an analysis of each component on the CERAD test, the working memory test revealed that metformin users required significantly more time to perform a certain task compared to nonusers. There was no significant association between metformin use and the progression of cognitive impairment.

Conclusions: Taken together, in this study, metformin treatment was not significantly associated with a higher risk of cognitive impairment in older adults with diabetes, after adjusting for age, gender, education duration, other variables and glycemic and metabolic controls. A well controlled study on a larger-scale is necessary in order to explain the effects and determine the association between metformin use and cognitive dysfunction more clearly.