Type 2 Diabetes, Change in Depressive Symptoms Over Time, and Cerebral Small Vessel Disease: Longitudinal Data of the AGES-Reykjavik Study

Abstract

Objective: Type 2 diabetes has been associated with depression. However, the underlying pathophysiological mechanisms remain unknown. Cerebral small vessel disease, a consequence of diabetes, may lead to depression. Therefore, we evaluated whether cerebral small vessel disease mediates the association between type 2 diabetes and higher depressive symptoms.

Research design and methods: We used longitudinal data from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, with examinations from 2002 to 2006 and 5 years later. Type 2 diabetes was defined as self-reported history of type 2 diabetes, use of blood glucose-lowering drugs, or fasting blood glucose level ≥7.0 mmol/L. Cerebral small vessel disease load was quantified in a composite score based on MRI-defined presence of high white matter hyperintensity volume, low total brain parenchyma volume, and subcortical infarcts, cerebral microbleeds, and large perivascular spaces. The 5-year change in the 15-item Geriatric Depression Scale score (GDS-15) was measured between baseline and follow-up.

Results: Included were 2,135 individuals without dementia and baseline depression (baseline age 74.5 [SD 4.6] years, 1,245 women [58.3%], and 197 [9.2%] with diabetes). The GDS-15 score increased 0.4 (SD 1.6) points over time. Baseline diabetes was associated with a greater increase in the GDS-15 score (β = 0.337; 95% CI 0.094; 0.579), adjusted for age, sex, education, and cardiovascular risk factors. Baseline cerebral small vessel disease and change of cerebral small vessel disease statistically significantly mediated a part of this association.

Conclusions: Type 2 diabetes is associated with a greater increase in depressive symptoms score over 5 years, and cerebral small vessel disease partly explains this association.

Figure 1

Association between type 2 diabetes at baseline and change in the GDS-15 score, and the mediating effect by the composite score of baseline cerebral small vessel disease (CVSD) (A) and the composite score of cerebral small vessel disease change (B). Total effect is the association between type 2 diabetes at baseline and change in the GDS-15 score without adjustment for the composite score, direct effect is the association between type 2 diabetes and change in the GDS-15 score after adjustment for the composite score, and indirect effect is the explained or mediated effect by the composite score. Associations are given as regression coefficients (β) and corresponding 95% CIs. All associations are adjusted for age, sex, education level, alcohol use, smoking history, BMI, hypertension, and total cholesterol–to–HDL cholesterol ratio.