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.