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

Katherine Samaras; Steve Makkar; John D. Crawford; Nicole A. Kochan; Wei Wen; Brian Draper; Julian N. Trollor; Henry Brodaty; Perminder S. Sachdev

doi:10.2337/dc20-0892

Epidemiology/Health Services Research

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

Katherine Samaras¹,²,³ ⇑,
Steve Makkar⁴,
John D. Crawford⁴,
Nicole A. Kochan⁴,
Wei Wen⁴,
Brian Draper⁴,⁵,
Julian N. Trollor⁴,⁶,
Henry Brodaty⁴,⁵ and
Perminder S. Sachdev⁴,⁷

¹Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
²Department of Endocrinology, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia
³St Vincent’s Clinical School, University of New South Wales Sydney, New South Wales, Australia
⁴Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales Sydney, New South Wales, Australia
⁵Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales Sydney, New South Wales, Australia
⁶Department of Developmental Disability Neuropsychiatry, University of New South Wales Sydney, New South Wales, Australia
⁷Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, New South Wales, Australia

Corresponding author: Katherine Samaras, k.samaras{at}garvan.org.au

Diabetes Care 2020 Nov; 43(11): 2691-2701. https://doi.org/10.2337/dc20-0892

Abstract

OBJECTIVE Type 2 diabetes (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 participants with diabetes compared with those not receiving metformin and those without diabetes.

RESEARCH DESIGN AND METHODS A prospective observational study was conducted of N = 1,037 community-dwelling older participants without dementia aged 70–90 years 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 2 years; a battery of tests measured executive function, memory, attention/speed, language, and visuospatial function individually. These were used to determine the measure of global cognition. Incident dementia was ascertained by a multidisciplinary panel. Total brain, hippocampal, and parahippocampal volumes were measured by MRI at baseline and 2 years (n = 526). Data were analyzed by linear mixed modeling, including the covariates of age, sex, education, BMI, heart disease, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage.

RESULTS Of n = 1,037, 123 had diabetes; 67 received metformin (DM+MF) and were demographically similar to those who did not (DM-noMF) and participants without diabetes (no-DM). DM+MF had significantly slower global cognition and executive function decline compared with DM-noMF. Incident dementia was significantly higher in DM-noMF compared with DM+MF (odds ratio 5.29 [95% CI 1.17–23.88]; P = 0.05).

CONCLUSIONS 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.

Footnotes

This article contains supplementary material online at https://doi.org/10.2337/figshare.12811583.

Received April 20, 2020.
Accepted August 11, 2020.

https://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.

View Full Text