Non-alcoholic fatty liver disease does not increase dementia risk though histology data might improve risk prediction

ABSTRACT Background and aims Non-alcoholic fatty liver disease (NAFLD) is common in the general population, but its association with dementia is unclear. We aimed to assess the risk of dementia related to NAFLD, and to determine whether histological parameters could improve the predictive capacity of dementia over conventional risk factors in patients with biopsy-proven NAFLD. Methods A retrospective matched cohort study of 656 NAFLD patients underwent liver biopsy at two hospitals between 1971 and 2009. Up to 10 individuals (controls) from the general population (n=6,436) were matched for age, sex and municipality to each patient. Dementia was ascertained from National registers until 2014. Using Cox regression, we estimated hazard ratios for dementia with 95% confidence intervals. In the biopsy cohort, the discriminative power of adding histological markers to a conventional risk model was assessed by Harrell’s C-index and compared with a likelihood-ratio test. Results During a mean follow-up of 19.7±8.7 years, 3.3% of the NAFLD patients and 4.9% of the controls developed dementia (p=0.07). Overall, NAFLD was not significantly associated with incident dementia. In the biopsy cohort, the model of conventional risk factors (age, sex, hypertension and cardiovascular diseases) had a C-index of 0.912 to predict incident dementia. Adding individual histological parameters significantly increased the prediction of dementia, with the most pronounced improvement for fibrosis stage (C-index=0.938, p Conclusions Although NAFLD was not associated with the risk of dementia, we found that adding histological markers to conventional risk model for dementia enhanced the predictive capacity, indicating a shared metabolic origin.