Associations Between Cerebral Amyloid Angiopathy, Cognitive Impairment, and Depressive Symptoms

Cerebral amyloid angiopathy (CAA) is associated with intracerebral hemorrhage, cognitive decline, and dementia. We examined (1) associations between CAA, cognitive impairment, and depressive symptoms; (2) whether depressive symptoms mediate the relationship between CAA and cognition; and (3) whether CAA neuroimaging markers predict depressive symptom severity.

Recruitment occurred through memory and stroke prevention clinics across 2 sites. Cross-sectional data from probable CAA and controls were analyzed. Neuropsychological tests were grouped into episodic memory, executive function, and processing speed domains. Scores ≥5 on the Geriatric Depression Scale: Short Form (GDS-15) defined "possible depression." Regression and mediation analyses examined associations among CAA status, cognition, and depressive symptoms, and in CAA, associations between neuroimaging biomarkers and GDS-15.

In 85 CAA (mean age 73.5; 35.3% female) and 83 controls (mean age 68.8; 62.7% female), CAA status was associated with poorer performance across cognitive domains. Higher GDS-15 scores were associated with poorer performance across domains. CAA participants had higher odds of "possible depression" (odds ratio 15.71; 95% CI 4.26-80.05, p < 0.001) and scored 2.71 times higher on the GDS-15 than controls (95% CI 2.10-3.51, p < 0.001). In mediation, "possible depression" accounted for significant proportions of the effect of CAA on episodic memory (11%; β = -0.14, 95% CI -0.30 to -0.03, p = 0.014) and executive function (9%; β = -0.14, 95% CI -0.30 to -0.02, p = 0.016), but not processing speed (2%; β = -0.04, 95% CI -0.18 to 0.08, p = 0.56). In 81 CAA participants, higher GDS-15 scores were associated with lower mean cortical thickness (count ratio [CR] 1.33 per SD decrease in thickness, 95% CI 1.09-1.62, p = 0.005), presence of cortical superficial siderosis (CR 2.04, 95% CI 1.35-3.09, p < 0.001), and higher CAA small vessel disease total score (CR 1.16, 95% CI 1.00-1.35, p = 0.047).

CAA participants exhibited greater depressive symptoms and poorer cognition than controls. Depressive symptoms mediated a small portion of the association between CAA and cognition. Cerebral cortex damage may underlie some depressive symptoms. Interventions targeting CAA-related neurodegeneration and treatment of depressive symptoms may support cognitive health in CAA.