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. PROSPERO CRD42018109185.