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 bloodbrain 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-I tem 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.