Metformin Could Slow Cognitive Decline, Reduce Dementia Incidence in Diabetics

September 24, 2020

Analysis of information from more than 1000 patients in Australia sheds light on the potential association between metformin use and slower cognitive decline in older individuals.

New research from an Australian aging study suggests a first-line diabetes treatment could also be slowing cognitive decline in older patients.

The study, which was conducted over a 6-year period, suggests those taking metformin experienced a slower cognitive decline and lower rates of dementia than those who did not use metformin.

"This study has provided promising initial evidence that metformin may protect against cognitive decline,” said study investigator Katherine Samaras, MBBS, PhD, Leader of the Healthy Ageing Research Theme at the Garvan Institute and endocrinologist at St Vincent's Hospital Sydney, in a statement. “While type 2 diabetes is thought to increase dementia risk by promoting degenerative pathways in the brain and nerves, these pathways also occur in others at risk of dementia and it is possible insulin resistance may be the mediator.”

With type 2 diabetics at a greater risk for a slew of other conditions and comorbidities, including dementia and cognitive decline, investigators sought to determine whether use of metformin would reduce the incidence of dementia and cognitive decline over an extended period of time. Part of the Sydney Memory and Ageing Study, the current study was designed as a prospective observational study of 1037 community-dwelling participants aged 70-90 without dementia at baseline.

Of note, patients were excluded from the study if they had dementia, a major neurological or psychiatric disease, or progressive malignancy. For the purpose of analysis, neuropsychological testing measuring cognitive function were performed every 2 years. Additionally, participants underwent a slew of tests designed to assess executive function, memory, attention-speed, language, and visuospatial function as individual components to determine global function. For the purpose of the study, investigators determined incident dementia through a multidisciplinary panel.

Investigators were also able to obtain total brain, hippocampal, and parahippocampal volumes through MRI measurements at baseline and 2 years for 526 patients. For the purpose of analysis, investigators used linear mixed models to examine potential associations between metformin use and cognitive decline. Investigators noted these models were adjusted for age, sex, education, BMI, heart disease, hypertension, stroke, smoking, and apolipoprotein Ee4 carriage.

Upon analysis, investigators identified 123 patients in the cohort of 1037 that were classified as having diabetes. Of these, 67 reported metformin use—investigators pointed out those receiving metformin were demographically similar to those who were not receiving metformin and those without diabetes. Results of the analysis suggest diabetics using metformin had significantly slower global cognition and executive function decline compared to diabetes not receiving metformin. Additionally, incident dementia was significantly higher in those with diabetes not receiving metformin compared to those with diabetes receiving metformin (OR, 5.29; 95% CI, 1.17-23.88; P=.05).

"While an observational study does not provide conclusive 'proof' that metformin is protective against dementia, it does encourage us to study this and other anti-diabetic treatments for dementia prevention,” said lead investigator Perminder Sachdev, MD, PhD, co-director of the Centre for Health Brain Aging at UNSW Sydney, in the aforementioned statement.

This study, “Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study,” was published in Diabetes Care.