Association of Atrial Electrophysiological Abnormalities With Cognitive Decline and Cerebrovascular Disease

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 ( P interaction <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 ( P interaction <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.