Abstract Body: Introduction: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage in elderly patients. Whether CAA is associated with isolated subdural hemorrhage (SDH), without an accompanying intracerebral hemorrhage, remains unclear. We therefore tested this relationship in a large, heterogeneous sample of patients from across the US.

Methods: We performed a retrospective cohort study using administrative claims data from hospitalizations in 11 states in the US between 2016 and 2019. Our study population was all hospitalized patients 50 years of age and older, consistent with the Boston criteria v2.0 age cut-off for the diagnosis of CAA. We divided this population into 3 groups: (a) those with a diagnosis of CAA, (b) those with other cerebrovascular disease without CAA, and (c) those without CAA or other cerebrovascular disease. The main outcome was a first-documented, isolated, non-traumatic SDH; we did not count SDH cases with a concurrent traumatic brain injury. The exposures and outcome were identified using previously validated ICD-10-CM diagnosis codes. Using Cox regression analyses, we compared the risk of incident SDH among the three groups after adjustment for demographics and comorbidities. In pre-specified sensitivity analyses, patients with a diagnosis of dementia at baseline were excluded.

Results: Among 8.5 million hospitalized patients, 2,335 had CAA and 600,646 had other cerebrovascular disease. During a median follow up of 2.0 years (IQR, 1.0-3.9), incident SDH occurred in 34 (1.5%) patients with CAA, 3,552 with other cerebrovascular disease (0.6%), and 35,425 (0.4%) without CAA or other cerebrovascular disease. In adjusted Cox regression analysis, there was an increased risk of incident SDH seen for CAA (HR, 3.1; CI, 2.2-4.4) and prevalent cerebrovascular disease (HR, 1.4; CI, 1.3-1.5). Findings were similar in sensitivity analyses excluding patients with dementia.

Conclusion: In a large, heterogeneous cohort, we found that CAA was associated with a 3-fold heightened risk of SDH. This risk appeared higher than that seen in patients with prevalent cerebrovascular disease. These findings further add to emerging evidence that CAA is a novel risk factor for isolated non-traumatic SDH.