Introduction: White matter hyperintensities (WMH), an MRI-based biomarker of cerebral small vessel disease and risk factor for stroke, has also been linked to depression and cognitive impairment. We examined whether depressive symptoms (not major depression which was exclusionary) can moderate the association between WMH and everyday functional activities in a real-world mixed clinical sample (i.e., Parkinson’s disease, Vascular Cognitive Impairment, Frontotemporal Dementia, Alzheimer’s disease) and cognitively normal older adults, with varying degrees of vascular burden. Method: We assembled a cross-sectional sample of patients with a recorded history of stroke and/or hypertension (N=299; mean age=71.5±9.8 years; % female=54.2) from the Sunnybrook Dementia Study. We used path analysis to test whether depressive symptoms (on the Cornell Scale for Depression (total=38)) moderated the association between WMH and function (Functional Rating Scale: FRS). Participants were grouped into low (n=129; score=0-4) and high (n=116; score=5-18) depressive symptoms using median split. History of stroke/hypertension, clinical dementia severity, age, and sex were included as covariates. Results: Higher WMH volume predicted greater severity on FRS (β=0.089, p=0.002), but depressive symptoms moderated the association between WMH and FRS. Specifically, higher WMH predicted greater FRS severity in the high depressive symptoms group (β=0.076, p=0.016) but not in the low (β=0.062,p= 0.249) group. Conclusions: The impact of cerebral small vessel disease on everyday life activities may vary depending on degree of depressive symptoms, with stroke or hypertension history included as covariates. Adults with significant cerebral small vessel disease burden, combined with depressive symptoms have a greater risk of being functionally dependent.

DEPRESSIVE SYMPTOMS MODERATE THE ASSOCIATION BETWEEN CEREBRAL SMALL VESSEL DISEASE AND FUNCTIONAL ACTIVITIES