Retrospective cohort study finds CAA increases dementia risk in elderly, indicating need for awareness in clinical practice.
Introduction: Cerebral amyloid angiopathy (CAA) is a frequent cause of hemorrhagic stroke in the elderly and is associated with an elevated risk of ischemic stroke. CAA also independently contributes to cognitive impairment and is often comorbid with Alzheimer’s Disease pathology. However, there are limited population-wide data on the risk of incident dementia following a clinical diagnosis of CAA, and the impact of ischemic and hemorrhagic stroke on dementia risk in CAA is not well characterized. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data between 2016-2022 from a nationally representative 5% sample of Medicare beneficiaries ≥65 years of age. The exposure variable was CAA. Stroke, a potential mediator/confounder, was defined as a composite of ischemic and hemorrhagic stroke. The primary outcome was dementia. CAA, stroke, and dementia were all identified using validated ICD-10-CM diagnosis codes. Patients with prevalent dementia were excluded. To study the relationship between CAA, stroke, and dementia, 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 diagnosis of CAA or stroke (reference group), 2) CAA only without a diagnosis of stroke, 3) stroke only without a diagnosis of CAA, and 4) both CAA and stroke. Stata version 18 and its multistate package were used for statistical analyses. Results: Of 1,909,365 beneficiaries in our cohort, 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 patients with CAA and 10.0% (95% CI, 10.0-10.1) in patients 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 state (Table 1). Conclusions: In a nationally representative cohort of Medicare beneficiaries, CAA was associated with a more than four-fold increased risk of incident dementia regardless of coexisting stroke; whereas stroke without CAA was associated with a smaller, two-fold, increase in risk of incident dementia.
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Bruce et al. (2026) studied this question.
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