- Cerebral amyloid angiopathy is associated with significantly poorer episodic memory, executive function, and processing speed, and markedly higher depressive symptom burden than controls.
- Depressive symptoms partially mediated CAA effects on episodic memory (11%) and executive function (9%), but not processing speed.
- Higher depression scores in CAA correlated with lower cortical thickness, cortical superficial siderosis, and greater small vessel disease burden.
Neurology. 2026 Sep 8;107(5):e218354. doi: 10.1212/WNL.0000000000218354. Epub 2026 Aug 5.
ABSTRACT
BACKGROUND AND OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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).
DISCUSSION: 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.
PMID:42555885 | DOI:10.1212/WNL.0000000000218354
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