Age at Diagnosis of Atrial Fibrillation and Incident Dementia.

Importance: Epidemiological evidence regarding the association between atrial fibrillation (AF) onset age and risk of incident dementia remains unexplored.

Objective: To examine whether age at AF diagnosis is associated with risk of incident dementia and its subtypes.

Design, Setting, And Participants: This prospective, population-based cohort study used data from UK Biobank, a public, open-access database in the UK with baseline information collected from 2006 to 2010. A total of 433 746 participants were included in the main analysis after excluding participants with a diagnosis of dementia or AF at baseline, missing data on covariates, or having dementia before AF onset during a median follow-up of 12.6 years. Data were analyzed from October to December 2022.

Exposures: AF diagnosis and age at AF diagnosis according to age groups (<65 years, 65-74 years, or ≥75 years).

Main Outcomes And Measures: Incident dementia, ascertained through linkage from multiple databases until December 31, 2021. Cox proportional hazards models and the propensity score matching method were adopted to estimate the association between AF onset age and incident dementia.

Results: Of 433 746 included participants, 236 253 (54.5%) were female, the mean (SD) age was 56.9 (8.1) years, and 409 990 (94.5%) were White. Compared with individuals without AF, 30 601 individuals with AF had a higher risk of developing all-cause dementia (adjusted hazard ratio [HR], 1.42; 95% CI, 1.32-1.52) and vascular dementia (VD; adjusted HR, 2.06; 95% CI, 1.80-2.36), but not Alzheimer disease (AD; adjusted HR, 1.08; 95% CI, 0.96-1.21). Among participants with AF, younger age at AF onset was associated with higher risks of developing all-cause dementia (adjusted HR per 10-year decrease, 1.23; 95% CI, 1.16-1.32), AD (adjusted HR per 10-year decrease, 1.27; 95% CI, 1.13-1.42), and VD (adjusted HR per 10-year decrease, 1.35; 95% CI, 1.20-1.51). After propensity score matching, individuals with AF diagnosed before age 65 years had the highest HR of developing all-cause dementia (adjusted HR, 1.82; 95% CI, 1.54-2.15), followed by AF diagnosed at age 65 to 74 years (adjusted HR, 1.47; 95% CI, 1.31-1.65) and diagnosed at age 75 years or older (adjusted HR, 1.11; 95% CI, 0.96-1.28). Similar results can be seen in AD and VD.

Conclusions And Relevance: In this prospective cohort study, earlier onset of AF was associated with an elevated risk of subsequent all-cause dementia, AD, and VD, highlighting the importance of monitoring cognitive function among patients with AF, especially those younger than 65 years at diagnosis.