Abstract

Introduction: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) contributes to the development of depression. A multi-marker CSVD score based on brain magnetic resonance imaging (MRI) could serve as a valuable tool for predicting the risk of developing vascular depression. This is important as depression can mimic cognitive impairment, dementia and is treatable. This study aimed to determine the relation of a MRI multi-marker CSVD score with incident depression in community-dwelling individuals. Methods: Framingham Heart Study participants from the Original and Offspring cohorts free of stroke, dementia and depression with available data on depression and CSVD ratings on MRI were included. Depression was defined as Center for Epidemiological Studies Depression scale score ≥16 or use of antidepressant medication. The multi-marker CSVD score was calculated by summing 1 point for individual CSVD markers present (covert brain infarcts, cerebral microbleeds, extensive white matter hyperintensities, high burden perivascular spaces, cortical superficial siderosis), ranging 0-5. Multivariable logistic regression models were used to relate the MRI-multi-marker CSVD score and incident depression in a primary analysis and individual CSVD biomarkers and depression in an exploratory analysis. Models were adjusted for age, sex, FHS cohort, time interval between MRI and clinic exam, body mass index, smoking, prevalent hypertension and diabetes. Results: In 1768 participants included (mean age 54.4±12.4 years, 54% male), the incidence of depression was 11% (median follow-up 6.0 years, IQR: 5.3-6.7). No CSVD score group had a statistically significant association with incident depression, however a CSVD score 3+ showed a trend towards increased odds of developing incident depression (OR 2.65 [0.87, 8.06], p =0.09). Among the individual CSVD markers, visible perivascular spaces had the highest odds for incident depression (OR 1.55 [0.96, 2.51] p =0.07). Conclusion: A higher multi-marker CSVD score might be associated with increased odds of incident depression. Further studies with a larger sample may help elucidate a potential association between this CSVD burden and onset of depression.

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