Association between atrial fibrillation and dementia, with a particular focus on early-onset dementia: a longitudinal population-based study in catalonia, spain

Abstract Introduction Some studies have suggested an independent association between atrial fibrillation (AF) and dementia, while others have failed to confirm this relationship. The strength of this association, as well as its interaction with stroke, remain controversial. Additionally, data on the Mediterranean population are lacking. Identifying sub-groups with the strongest association can help understand the drivers of this association and inform targeted preventive interventions. Purpose We aimed to assess the independent association between AF and incident dementia in Catalonia, Spain. Methods Population-based observational study including individuals who, in 2007, were ≥45 years old and had no prior diagnosis of dementia. The population was sourced from the System for the Development of Research in Primary Care, which provides anonymized data on over 80% of the Catalan population. Incident dementia cases were defined using a validated approach based on ICD-10 codes and prescription data for dementia-related medications. Early-onset dementia (EOD) was defined as a diagnosis occurring before age 65. The follow-up period extended over 15 years, from 2007 to 2021. Predictors of incident dementia were evaluated using Cox regression models. Results The study included 2,520,839 individuals with an average follow-up of 13 years. At baseline, 79,820 patients (3.25%) had a recorded diagnosis of AF. During follow-up, AF patients had a significantly higher crude incidence of dementia (17.4 vs 5.5 cases per 1000 person-years), and AF was a strong predictor of dementia at univariate analysis (HR 3.39, p<0.001). In multivariable analyses adjusting for potential confounders, AF remained a statistically significant but weak predictor (HR 1.04, p<0.001). Age significantly interacted in the association between AF and dementia. In pre-specified analyses stratified by age, the strength of the association progressively weakened with increasing age: the HR declined from 3.29 in patients aged 45–50 to 0.99 in those over 90. The association lost statistical significance from age 70 onwards. By contrast, in patients under 70, AF independently increased the risk of dementia by 21% (adjusted HR 1.21, p<0.001). The strongest association was observed for EOD (adjusted HR 1.36, p<0.001). Sensitivity analyses that censored prevalent cases of stroke at baseline and incident stroke during follow-up yielded similar results, with the highest association once again observed with EOD (adjusted HR 1.52, p<0.001). Conclusions This is the largest European population-based study evaluating the association between AF and dementia. In the overall population, AF was an independent but relatively weak predictor of dementia. The association between AF and dementia was stronger in patients under 70 and was maximal for EOD. These results remained qualitatively unchanged censoring for prevalent and incident stroke.Study flowchart Analysis of AF-dementia association