Identification and characterization of intracerebral hemorrhage events in elderly veterans with alzheimer’s disease in the veterans affairs healthcare system

Cerebral amyloid angiopathy (CAA) and hypertensive (HTN) small vessel disease are causes of spontaneous intracerebral hemorrhage (ICH). We identified ICH rates in patients with all-cause mild cognitive impairment (MCI) or Alzheimer's disease (AD), and explored feasibility of using location-based approach to differentiate CAA- and HTN-related ICH using comorbidities in electronic health records (EHRs). This administrative study combined Veterans Affairs Healthcare System plus Centers for Medicare and Medicaid Services (VAHS/CMS) databases. Patients with MCI/AD aged ≥ 50 years (2016-2023) were 1:1 matched to non-MCI/AD controls. Inpatient primary discharge International Classification of Diseases-10th Edition (ICD-10) codes identified acute ICH; anatomical location within codes classified events as likely CAA- or HTN-related ICH. Incidence rates of ICH after MCI/AD were summarized. Cluster analysis of variables related to ICH was used to describe whether data-driven groupings matched clinician-postulated classifications. The MCI/AD cohort (n = 747,475) and controls were aged 77.7 ± 10.1 years (96% men, 75-76% White, 87-88% non-Hispanic). Demographic- and comorbidity-adjusted rates of ICH/1000 person-years were 0.84 (overall), 1.05 (MCI/AD), and 0.68 (non-MCI/AD). Adjusted events/1000 person-years were higher in MCI/AD vs. non-MCI/AD cohorts: CAA-related ICH, 0.19 vs. 0.12 (Incidence Rate Ratio (IRR) 1.63; P < 0.001); HTN-related ICH, 0.16 vs. 0.12 (IRR 1.35; P < 0.001); non-specific-ICH, 0.68 vs. 0.43 (IRR 1.59; P < 0.001). Hierarchical clustering analysis of our cohorts revealed an association of CAA-related ICH with older age, cardiovascular and rheumatic disorders, and an association of HTN-related ICH with cerebrovascular disease, hypertension and diabetes. In sum, the estimated incidence of ICH over the study period was 0.84/1000 person-years. CAA-related ICH incidence in MCI/AD was 63% greater than that in controls. Outcomes from cluster analysis are consistent with ICD-based CAA- vs. HTN-related ICH classifications. These findings support future exploration of using ICD coding-based ICH event identification in EHRs and claims databases for epidemiological studies.