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

Objective:

Evidence is mixed as to whether periventricular or deep white matter hyperintensities (WMHs) increase the risk for depressive symptoms, partly because of heterogeneity in depression measurement, short follow-up, and confounding by prodromal dementia. The study objective was to evaluate WMH volume in relation to discrete depressive symptoms over 10 years, stratifying by incident depression and dementia.

Methods:

In this prospective longitudinal cohort study of a representative population sample from Dijon, France, 1,440 participants aged 65-80 years (median age: 72 years; 59.5% women) without depression, dementia, or stroke at baseline were studied. Baseline T2-weighted images were obtained in a 1.5-T scanner to quantify WMHs (log cm³). Clinic visits were performed up to five times in a 10-year period to assess incident neurologic diseases and comorbidities. Depressive symptoms were measured with the Center for Epidemiologic 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]: 0.02-0.29; p = 0.026). Deep WMH volume was uniquely associated with depressed affect among incident dementia cases (β = 0.36; 95% CI: 0.05-0.68; p = 0.025). WMH volume (periventricular, deep, and total) was associated with interpersonal problems among persons who developed dementia with depression.

Conclusion:

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.