Association between non‐alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study

Abstract

Background and Aims Little is known about the association between non‐alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. Methods We conducted a nationwide cohort study involving 4 031 948 subjects aged 40–69 years who underwent ≥2 health check‐ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non‐NAFLD (HSI <30 at all check‐ups) and NAFLD (HSI >36 at one or more check‐ups). Dementia defined by ICD‐10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. Results At baseline, 31.3% had NAFLD. During the median follow‐up of 9.5 years, 138 424 in NAFLD group and 69 982 in non‐NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non‐NAFLD group on multivariable‐adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity‐score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non‐obese NAFLD subjects (BMI <25 kg/m2, HR, 1.09; p < .001) than obese NAFLD subjects. Conclusions This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non‐obese NAFLD subjects.

Non‐alcoholic fatty liver disease and the risk of dementia

“…A total of four observational studies were included in the meta-analysis through systematic literature search from PubMed, Embase and Web of science until 20 April 2022. 1,[4][5][6] Pooled analysis showed that NAFLD was not linked with a higher risk of dementia on Random effect model (HR, 1.02; 95% CI, 0.91-1.14; Figure 1A), which was consistent with the results of the 'leave-one-out' sensitivity analysis (Figure 1B).…”

“…With great interest, we read the recent study by Kim and coworkers showing that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of dementia in a nationwide cohort study. 1 We thank them for their significant work for clinical practice, but there exist some potential pitfalls which may affect the credibility of the results. Firstly, the baseline characteristics between NAFLD and non-NAFLD group were severely unbalanced, although multivariable analysis and propensity score matching analysis was performed to reduce confounders.…”

Nonalcoholic Fatty Liver Disease and Altered Neuropsychological Functions in Patients with Subcortical Vascular Dementia

“…By contrast, a recent nationwide study found that NAFLD is associated with an increased risk of dementia [ 101 ]. The association was more pronounced among females and nonobese NAFLD subjects [ 89 ].…”

Non‐alcoholic fatty liver disease and the risk of dementia—Authors' reply

“…We thank Dr. Zhou et al for their thorough review of our article. 1 We agree that the different baseline characteristics in non-alcoholic fatty liver disease (NAFLD) and non-NAFLD groups in investigating the risk of dementia deserve some attention. Yet, we are afraid that the baseline characteristics of these two groups can hardly be comparable in the real-world set.…”