Association of Atrial Electrophysiological Abnormalities With Cognitive Decline and Cerebrovascular Disease

J Am Heart Assoc. 2026 Jan 6;15(1):e045054. doi: 10.1161/JAHA.125.045054. Epub 2025 Dec 30.

Abstract

Background: Atrial electrophysiological abnormalities (AEA) are associated with cognitive dysfunction. We evaluated the associations of AEA with longitudinal cognitive decline and incident dementia and investigated underlying mechanisms.

Methods: In subjects without atrial fibrillation followed prospectively for 5 years, 12-lead ECGs were evaluated for AEA, defined as the presence of sinus node dysfunction (SND), frequent premature atrial complexes, advanced interatrial block (a-IAB), or P-terminal force in V1 (>40 mm*ms). Rate of decline in global cognition (Z-score averaged from 6 cognitive domains), Clinical Dementia Rating-Sum of Boxes score, and associations with cerebrovascular disease on neuroimaging and circulating biomarkers of neurodegenerative disease were determined.

Results: Among 358 subjects (age 73.3±7.6 years, 55% female, 47% dementia), 188 (53%) had AEA (94 SND, 6 frequent premature atrial complexes, 52 a-IAB, 92 P-terminal force in V1 >40 mm*ms). Compared with non-AEA, AEA was associated with accelerated decline in both global cognition and Clinical Dementia Rating-Sum of Boxes score (Pinteraction<0.05), 2 times increased risk of dementia in competing risk analyses, and increased burden of cortical infarcts, lacunes, and cerebral microinfarcts (P<0.05). Among AEA subtypes, SND (versus non-SND) and a-IAB (versus non-a-IAB) both associated with accelerated decline in global cognition and Clinical Dementia Rating-Sum of Boxes score (Pinteraction<0.05). a-IAB was associated with 3 times increased risk of incident ischemic stroke and P-terminal force in V1 with increased burden of lacunes. SND was associated with increased burden of cerebral microinfarcts and cerebral microbleeds, incident cerebral microbleeds, higher circulating pTau-181 levels, and increased odds of Alzheimer disease among subjects with preexisting dementia (P<0.05).

Conclusions: AEA is associated with worse cognitive trajectories and increased cerebrovascular disease burden. These associations may be underpinned by AEA-subtype-specific mechanisms.

Keywords: ECG; atrial cardiomyopathy; cognitive decline; dementia; interatrial block; sinus node dysfunction; stroke.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Premature Complexes* / complications
  • Atrial Premature Complexes* / epidemiology
  • Atrial Premature Complexes* / physiopathology
  • Biomarkers / blood
  • Cerebrovascular Disorders* / diagnosis
  • Cerebrovascular Disorders* / epidemiology
  • Cerebrovascular Disorders* / physiopathology
  • Cognition*
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / epidemiology
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Electrocardiography
  • Female
  • Heart Atria* / physiopathology
  • Humans
  • Incidence
  • Male
  • Prospective Studies
  • Risk Factors

Substances

  • Biomarkers