Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology

Abstract INTRODUCTION Cerebral amyloid angiopathy (CAA) often accompanies dementia‐associated pathologies and is important in the context of anti‐amyloid monoclonal therapies and risk of hemorrhage. METHODS We conducted a retrospective neuropathology‐confirmed study of 2384 participants in the National Alzheimer Coordinating Center cohort (Alzheimer's disease [AD], n = 1175; Lewy body pathology [LBP], n = 316; and mixed AD and LBP [AD‐LBP], n = 893). We used logistic regression to evaluate age, sex, education, APOE ε4 , neuritic plaques, and neurofibrillary tangles (NFTs) in CAA risk. RESULTS APOE ε4 increased CAA risk in all three groups, while younger age and higher NFT stages increased risk in AD and AD‐LBP. In AD‐LBP, male sex and lower education were additional risk factors. The odds of APOE ε4 carrier homozygosity related to CAA was higher in LBP (25.69) and AD‐LBP (9.50) than AD (3.17). DISCUSSION AD and LBPs modify risk factors for CAA and should be considered in reviewing the risk of CAA. Highlights Lewy body pathology modifies risk factors for cerebral amyloid angiopathy (CAA) when present along with Alzheimer's disease (AD) neuropathology. In the context of anti‐amyloid monoclonal therapies and their associated risks for hemorrhage, the risk of underlying CAA in mixed dementia with Lewy body pathology needs to be considered.