Clinical Predictors of Severe Cerebral Amyloid Angiopathy and Influence of APOE Genotype in Persons With Pathologically Verified Alzheimer Disease

IMPORTANCE Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited. OBJECTIVE To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE 4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD. MAIN OUTCOMES AND MEASURES Prevalence of demographic characteristics and the APOE epsilon 4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA. RESULTS Persons with severe CAA compared with those without CAA were more likely to carry an APOE epsilon 4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE epsilon 4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7). CONCLUSIONS AND RELEVANCE Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in beta-amyloid trafficking.