Inflammation and Cognitive Decline: A Population‐Based Cohort Study Among Aging Adults With Atrial Fibrillation

BACKGROUND: Despite associations between atrial fibrillation (AF) and cognitive decline independent of stroke, pathways underlying this relationship remain unclear. Inflammatory markers, such as CRP (C-reactive protein), are associated with blood-brain barrier (BBB) permeability, potentially leading to neuroinflammation and neurodegeneration. We estimated associations of CRP with cognitive impairment and death in aging adults with AF. METHODS: Adults aged ≥45 years with prevalent AF and no cognitive impairment were identified from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (N=30 239). Plasma CRP was measured at baseline and cognitive status measured annually using the Six-Item Screener. Competing risks Cox proportional hazards regression was used to estimate cause-specific hazard for cognitive impairment (Six-Item Screener score ≤3). Cognitive trajectories were identified using latent class growth models and adjusted binomial logistic regression used to estimate associations between CRP and cognitive trajectories, with interactions by sex. RESULTS: Among 2109 participants, 285 developed cognitive impairment and 786 died over a median 9-year follow-up. A doubling of baseline CRP levels was associated with increased death (hazard ratio HR, 1.13 95% CI, 1.08-1.19) but not incident cognitive impairment (HR, 0.98 95% CI, 0.91-1.04). Latent class analyses identified 2 unique cognitive trajectories: 91% had a stable trajectory, while 9% showed progressive decline. Sex-specific models showed a 9% increased odds of progressive cognitive decline in men (odds ratio, 1.09 95% CI, 1.01-1.17) but not women (odds ratio, 1.04 95% CI, 0.97-1.12). CONCLUSIONS: Higher CRP was associated with cognitive impairment in aging men with AF, highlighting inflammation-mediated blood-brain barrier dysfunction as a potential pathway linking AF to cognitive decline.