Multi-marker cerebral small vessel disease score and risk of incident depression: The Framingham Heart Study

The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) contributes to the development of depression. This study examined the relationship between a multi-marker CSVD score derived from brain magnetic resonance imaging (MRI) with incident depression in community-dwelling individuals.

Framingham Heart Study (FHS) participants free of stroke, dementia, and depression with available data on CSVD MRI markers were included. The CSVD score was calculated by summing one point for each individual CSVD marker: covert brain infarcts, cerebral microbleeds, white matter hyperintensities, visible perivascular spaces (PVS) and cortical superficial siderosis, ranging 0-5. Depression was defined as Center for Epidemiological Studies Depression scale score ≥ 16 or antidepressant used. Multivariable logistic regression models were used to relate the CSVD score and individual markers to incident depression. Models were adjusted for age, sex, FHS cohort, time interval between MRI and clinic exam, and regular vascular risk factors.

Among 1768 participants, (mean age 54.4 ± 12.4 years, 54 % male), 11 % developed depression (median follow-up 6.0 years, IQR: 5.25-6.70). No CSVD score group, or individual marker had a statistically significant association with incident depression. However, both a CSVD score of 3+ (OR: 2.72, 95 %, CI 0.90, 8.19, p = 0.09) and the presence of visible PVS (OR: 1.56, CI 0.97, 2.52, p = 0.07) showed a trend towards increased odds of developing depression.

A high CSVD burden and the presence of visible PVS may be related to incident depression. Validation in larger and more diverse cohorts is required.