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

Abstract

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.