ABSTRACT NUMBER: ESOC2026A1589 CEREBRAL AMYLOID ANGIOPATHY AND RISK OF INCIDENT DEMENTIA

Abstract Background and aims There are limited population-wide data on the risk of incident dementia following a diagnosis of cerebral amyloid angiopathy (CAA), and the impact of ischemic and hemorrhagic stroke on dementia risk in the setting of CAA is not well characterized. Methods We performed a retrospective cohort study using Medicare data (≥65 years) from 2016-2022. The exposures were CAA and stroke (ischemic or hemorrhagic). The primary outcome was dementia. The exposures and outcomes were identified using validated ICD-10 diagnosis codes. Subjects with prevalent dementia were excluded. We used a multistate Cox proportional hazards model adjusted for demographics and vascular risk factors to determine risks of incident dementia associated with four mutually exclusive states: 1) no CAA or stroke (reference), 2) CAA only without stroke, 3) stroke only without CAA, and 4) both CAA and stroke. Results Of 1,909,365 patients, 752 (0.04%) had a diagnosis of CAA. The 5-year cumulative incidence of dementia was 42.0% (95% CI, 39.0-53.9%) in subjects with CAA and 10.0% (95% CI, 10.0-10.1) in subjects without CAA (Figure 1). In multistate Cox proportional hazards model, CAA with stroke (HR, 4.5; 95% CI, 3.3-6.2), CAA without stroke (HR, 4.3; 95% CI, 3.6-5.1), and stroke without CAA (HR, 2.4; 95% CI, 2.3-2.4) were associated with increased risk of dementia compared to the reference group (Table 1). Conclusions In a nationally representative US cohort, CAA led to 4-fold increased risk of incident dementia regardless of coexisting stroke, while stroke without CAA was associated with a smaller increase in risk of incident dementia. Conflict of interest Dr. Murthy: grants from NIH, consultancy fees from Alnylam and CarePoint. Dr. Bruce: nothing to disclose. Ms. Zhang: nothing to disclose. Dr. Liberman: nothing to disclose. Dr. Navi: nothing to disclose. Dr. Merkler: nothing to disclose. Dr. Chiang: grants from NIH. Dr. Payabvash: grants from the American Heart Association and NIH. Dr. Falcone: grants from the AHA and NIH. Dr. Roh: grants from the NIH. Dr. Iadecola: nothing to disclose. Dr. Kamel: deputy editor of JAMA Neurology, grants from NIH, steering/executive committees for Medtronic, Janssen, and Javelin Medical; endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. Figure 1 - belongs to Results Table 1 - belongs to Conclusions