Arrhythmias, dementia risk, and neurodegeneration: a cohort study

BACKGROUND AND AIMS: Evidence linking arrhythmias to dementia predominantly focuses on atrial fibrillation/flutter (AF), leaving non-AF subtypes under-researched. This study investigated associations of multiple incident and accumulated arrhythmia exposures with dementia and brain magnetic resonance imaging (MRI) to address these gaps. METHODS: UK Biobank participants without baseline arrhythmias, dementia, or organic central nervous system diseases were included. Cox models estimated associations of incident arrhythmia (AR), AF, bradyarrhythmia/conduction block (Brady/Block), ventricular arrhythmia (VA), and accumulated arrhythmia exposure (types) with all-cause, vascular and Alzheimer's dementia. Specific subtypes-including atrioventricular block (AVB), sinus node dysfunction (SND), and bundle branch block (BBB)-were also evaluated. Arrhythmia-related brain MRI alterations were analysed. RESULTS: Among 391 078 participants (median follow-up 13.35 years), 50 243 (12.85%) developed incident AR (AF, n = 33 182; Brady/Block, n = 21 244; VA, n = 6296), and 10 564 (2.70%) developed all-cause dementia (vascular, n = 2034; Alzheimer, n = 4329). Incident AR, AF, Brady/Block, and VA were independently associated with increased risk of all dementia outcomes (fully adjusted Model 3). Accumulated arrhythmia exposure exhibited a positive dose-response relationship with dementia risk, driven largely by AF+Brady/Block. Concurrent AF and AVB/SND (or BBB) showed higher dementia risk than either exposure alone, whereas pacemaker implantation related to lower risk than AVB/SND without pacing. These associations remained robust to incident stroke or cardiac arrest, genetic dementia risk, baseline cognition, and sensitivity analyses. Non-AF arrhythmias provided incremental predictive value beyond conventional risk factors, similar to AF. Brain MRI analysis revealed arrhythmia-related neurodegenerative changes, including brain atrophy, choroid-plexus enlargement, and white-matter injury. CONCLUSIONS: Incident arrhythmias (both AF and non-AF) exhibit independent and accumulated associations with dementia risk and consistent neurodegeneration. These findings extend the arrhythmia-dementia association beyond AF and suggest multi-arrhythmic framework for dementia risk assessment.