NAFLD does not increase the risk of incident dementia: A prospective study and meta-analysis

The association between nonalcoholic fatty liver disease (NAFLD) and incident dementia remains unclear. This study aimed to explore whether NAFLD was associated with the risk of incident dementia. We conducted a prospective analysis of 179,222 UK Biobank participants. NAFLD was diagnosed based on the fatty liver index. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of NAFLD for incident dementia. The results from this and six previous prospective studies were combined in meta-analyses. During a median follow-up of 12.4 years (2,149,839 person-years), 4950 incident dementia cases, including 2318 Alzheimer's disease (AD) cases and 1135 vascular dementia (VD) cases, were identified. There was no significant association between NAFLD and the risks of all-cause dementia (HR: 0.97, 95% CI: 0.90-1.06; P = 0.528). NAFLD was also not significantly associated with AD or VD (HR: 0.95, 95% CI: 0.84-1.07, P = 0.401; HR: 1.03, 95% CI: 0.88-1.22, P = 0.689, respectively). Our meta-analyses of prospective studies included 879,749 subjects. The pooled HR of NAFLD for all-cause dementia was 1.01 (95% CI: 0.94-1.08), and that for VD was 0.99 (95% CI: 0.86-1.13). All included cohort studies were of high quality as assessed by the Newcastle‒Ottawa scale. We found no evidence of an association between NAFLD and incident dementia.