White Matter Lesions are Associated with Specific Depressive Symptom Trajectories among Incident Depression and Dementia Populations: the Three-City Dijon MRI Study

Abstract Objectives Evidence is mixed as to whether periventricular or deep white matter hyperintensities (WMH) increase the risk for depressive symptoms, partly because of heterogeneity in depression measurement, short follow-up, and confounding by prodromal dementia. Our objective was to evaluate WMH volume in relation to discrete depressive symptoms over 10 years, stratifying by incident depression and dementia. Design Prospective longitudinal cohort study. Setting Representative population sample from Dijon, France. Participants 1440 participant's age 65-80 years (median age 72 years, 59.5% female) without depression, dementia or stroke at baseline. Measurements Baseline T2-weighted images were obtained in a 1.5-Tesla scanner to quantify WMH (log cm3 ). Clinic visits were performed up to 5 times in a 10-year period to assess incident neurological diseases and comorbidities. Depressive symptoms were measured with the Center for Epidemiological Studies-Depression scale and converted to factor z-scores representing; somatic symptoms, depressed affect, low positive affect, and interpersonal problems. Results Periventricular WMH volume was uniquely associated with low positive affect among incident depression cases (β = 0.15; 95% confidence interval [CI] 0.02 to 0.29, p = 0.026). Deep WMH volume was uniquely associated with depressed affect among incident dementia cases (β = 0.36; 95% CI 0.05 to 0.68, p = 0.025). WMH volume (periventricular, deep and total) was associated with interpersonal problems among persons who developed dementia with depression. Conclusions The findings highlight that regional WMH volumes and specific depressive symptoms have clinical and prognostic relevance to help differentiate between persons at risk for depression and dementia.