Abstract
INTRODUCTION: Heart failure (HF) and atrial fibrillation (AF) have been associated with a higher risk of Alzheimer's disease (AD). Whether HF and AF are related to AD by enhancing AD neuropathological changes is unknown. METHODS: We applied network analyses and multiple logistic regression models to assess the association between HF and AF with severity of AD neuropathology in patients from the National Alzheimer's Coordinating Center database with primary neuropathological diagnosis of AD. RESULTS: We included 1593 patients, of whom 129 had HF and 250 had AF. HF and AF patients were older and had milder AD pathology. In the network analyses, HF and AF were associated with milder AD neuropathology. In the regression analyses, age (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.93-0.95 per 1-year increase in age, P < .001) and the interaction term HF × AF (OR 0.61, 95% CI 0.40-0.91, P = .014) were inversely related to severe AD pathology, whereas APOE ε4 genotype showed a direct association (OR 1.68, 95% CI 1.31-2.16). Vascular neuropathology was more frequent in patient with HF and AF patients than in those without. DISCUSSION: HF and AF had milder AD neuropathology. Patients with milder AD lived longer and had more exposure to vascular risk factors. HF and AF patients showed a higher frequency of vascular neuropathology, which could have contributed to lower the threshold for clinically evident dementia.