Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial

Abstract

Aims: The association between diabetes and cognitive decline (CD) and dementia has been well-documented. This study estimated the associations between risk factors and CD/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death.

Materials and methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression.

Results: During a median five-year follow-up, 1,827 participants (43.2% women) had CD/dementia (1,718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had a lower odds of CD/dementia than men (Odds Ratio (OR) (95% confidence interval), 0.88 (0.77, 1.00)); older age, higher total cholesterol, HbA1c , waist circumference, waist-to-height ratio, moderately increased ACR (Albumin-Creatinine Ratio), stroke/transient ischemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women-to-men Ratio of Odds Ratios (ROR), 1.05 (1.00, 1.10) per 5 cm) and presence of anxiety/depression (ROR, 1.28 (1.01, 1.63)) were associated with greater OR for CD/dementia in women than men.

Conclusions: Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms which underlie these sex differences. This article is protected by copyright. All rights reserved.