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

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posted on 2020-06-11, 14:59 authored by Sytze P Rensma, Thomas T van Sloten, Jennifer Ding, Sigurdur Sigurdsson, Coen DA Stehouwer, Vilmundur Gudnason, Lenore J Launer
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.


This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Van Sloten is supported by a VENI research grant (916.19.074) from The Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMw), and by a Dutch Heart Foundation research grant (2018T025). The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.


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