Arrhythmias, dementia risk, and neurodegeneration: a cohort study

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.

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.

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.

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.