Sex differences in atrial fibrillation and progression to dementia
Authors: Wood K A , Han F , Ko Y A , Wharton W 
Published: July 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The National Institute of Aging (NIA) is a division of the U.S. National Institutes of Health (NIH)

Background
Atrial fibrillation (AF) is recognized as an independent risk factor for cognitive disease such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Women with AF experience more symptoms and worse outcomes of AF and stroke than men. Greater understanding is needed about whether sex differences exist in AF-related dementia incidence and prevalence.

Purpose
To address sex differences in AF-related cognitive disease, we examined disease prevalence and progression among adults with and without AF in the U.S. National Alzheimer’s Coordinating Center (NACC) cohort.

Methods
Data freeze/extraction of NACC data (N= 43,630) took place March 2021. Participants with ≥ 3 annual visits, diagnostic data, and AF status (self-reported or clinically diagnosed) were included. Cognition status was determined at each visit as normal, MCI, or dementia. Five domains evaluated by neuropsychological testing included attention, language, memory, executive functioning, and global cognition. Multinomial logistic regression and Cox proportional hazard model were used to examine association between AF and baseline cognitive diagnosis and time to progression in cognitive diagnosis, respectively. Covariates included age, sex, race, education, BMI, smoking, depression, hypertension, diabetes, hypercholesterolemia, heart failure, stroke, and sleep apnea. Interactions with sex were examined in all models.

Results
4,593 participants had AF at baseline. AF participants were 46% female, mean age 78.5, 81% White, 8% Black, 11% other ethnicities. There were significant declines in 3 of 5 cognitive domains (executive function, verbal ability, and memory) among participants with AF compared to those without AF. AF is associated with higher odds of having MCI (OR 3.43 [1.55, 7.55] in females; OR 1.73 [0.81, 3.71] in males) and dementia (OR 3.00 [1.22, 7.38] in females; OR 1.60 [0.87, 2.97] and in males). Among the 13,683 subjects included in the survival analysis, 4066 (30%) progressed from normal cognition to MCI or dementia and 2895 (21%) developed dementia with median follow-up of 3.98 years. Women with AF had higher risk of more rapid disease progression (HR 1.21 [1.04, 1.40]) compared to women without AF, but the association was not significant in men (HR 0.96 [0.83, 1.11]). AF was significantly associated with faster transition from normal cognition to MCI (HR 1.17 [1.03, 1.33]) and from MCI to vascular dementia (HR 2.57 [1.63, 3.95]) but not MCI to AD.

Conclusions
Women with AF are at higher risk of MCI and dementia with faster transition from normal cognition to MCI and dementia than women without AF or men with and without AF. Future research should focus on early identification of those individuals with AF at highest risk of cognitive disease and development of interventions to prevent or slow AF-related MCI and vascular dementia.