Type 2 diabetes, change in depressive symptoms over time, and cerebral small vessel disease – Longitudinal data of the AGES-Reykjavik Study

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-Reykjavik Study, with examinations from 2002/2006 and five 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. 5-year change in 15-item Geriatric Depression Scale score (GDS-15) was measured between baseline and follow-up.

Results: 2,135 individuals without dementia and baseline depression were included (baseline age 74.5 years [SD 4.6], 1,245 [58.3%] women and 197 [9.2%] with diabetes). The GDS-15 score increased 0.4 points (SD 1.6) over time. Baseline diabetes was associated with greater increase in 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 in part explains this association.