Cerebral Small-Vessel Disease and Risk of Incidence of Depression: A Meta-Analysis of Longitudinal Cohort Studies

Background Results of several longitudinal cohort studies suggested an association between cerebral small-vessel disease and depression. Therefore, we performed a meta-analysis to explore whether cerebral small-vessel disease imparts increased risk for incident depression. Methods and Results We searched prospective cohort studies relevant to the relationship between cerebral small-vessel disease and incident depression published through September 6, 2019, which yielded 16 cohort studies for meta-analysis based on the relative odds ratio (OR) calculated with fixed- and random-effect models. Baseline white matter hyperintensities (WMHs) (pooled OR, 1.37; 95% CI, 1.14-1.65), enlarged perivascular spaces (pooled OR, 1.33; 95% CI, 1.03-1.71), and cerebral atrophy (pooled OR, 2.83; 95% CI, 1.54-5.23) were significant risk factors for incident depression. Presence of deep WMHs (pooled OR, 1.47; 95% CI, 1.05-2.06) was a stronger predictor of depression than were periventricular WMHs (pooled OR, 1.31; 95% CI, 0.93-1.86). What's more, the pooled OR increased from 1.20 for the second quartile to 1.96 for the fourth quartile, indicating that higher the WMH severity brings greater risk of incident depression (25th-50th: pooled OR, 1.20; 95% CI, 0.68-2.12; 50th-75th; pooled OR, 1.42; 95% CI, 0.81-2.46; 75th-100th: OR, 1.96; 95% CI, 1.06-3.64). These results were stable to subgroup analysis for age, source of participants, follow-up time, and methods for assessing WMHs and depression. Conclusions Cerebral small-vessel disease features such as WMHs, enlarged perivascular spaces, and cerebral atrophy, especially the severity of WMHs and deep WMHs, are risk factors for incident depression.