Cognitive Trajectories and Incident Atrial Fibrillation in the ASPREE Cohort

Background:Atrial fibrillation (AF) is associated with aging and increased risk of stroke and dementia. We examined the association between incident AF and cognitive trajectories in older adults using longitudinal data from the ASPirin in Reducing Events in the Elderly (ASPREE) study. Methods:ASPREE was a multi-center randomized, double-blind, placebo-controlled trial of low-dose (100 mg) aspirin in healthy older adults. In this analysis, participants were aged ≥70 years with no history of cardiovascular disease, AF, or a diagnosis of dementia. We used a case ascertainment approach to identify participants with new onset of probable AF over trial participation, defined by new anticoagulant use, incident medically documented diagnosis, or irregular heart rate at study visits prompting diagnosis. We generated z -scores for cognitive assessments for global cognition (3MS, Modified Mini-Mental State Examination), verbal fluency/executive function (Controlled Oral Word Association Test, COWAT-F), delayed memory (Hopkins Verbal Learning Test-Revised, HVLT-R), and attention/processing speed (Symbol Digit Modalities Test, SDMT). Baseline cognition and trajectories were compared between probable AF and no AF (control group) using linear mixed-effects models. Results:Of 14,577 participants (mean age = 75.2 ± 4.3 years; 57.8% female), 978 (6.7%) developed probable AF. Baseline cognitive scores did not differ between groups. Compared to controls, those with AF showed greater decline over five years: 0.12 z -score (95% CI: 0.05, 0.20) in 3MS, 0.10 (95% CI: 0.07, 0.12) in COWAT, 0.10 (95% CI: 0.10, 0.16) in SDMT, and 0.11 (95% CI: 0.08, 0.14) in HVLT. APOE ℰ4 allele carriage was associated with greater decline among those with AF. Conclusions:In initially healthy older adults, those who developed AF had comparable cognitive profiles at baseline but exhibited greater cognitive decline over 5 years than those who did not. A diagnosis of AF may be a trigger for cognitive evaluation in older individuals. Clinical Trial Registration:www.clinicaltrials.gov/study/NCT01038583.