Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals

Aims
To systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment.

Methods and results
PubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25–1.53, I² = 90.3%; follow-up 3.8–25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66–3.74, I² = 0.0%; follow-up 0.25–3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11–1.73, I² = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58–2.64, I² = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke.

Conclusion
Atrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke.