Metabolic dysfunction-associated steatotic liver disease, metabolic alcohol-related liver disease, and incident dementia: a nationwide cohort study : MASLD, MetALD, and dementia risk.

BACKGROUND

The relationship between the newly proposed steatotic liver disease (SLD) subtypes-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic alcohol-associated liver disease (MetALD)-and dementia is understudied. We evaluated the dementia risk associated with these subtypes.

METHODS

This retrospective cohort study included 296,001 participants aged over 60 who underwent health examinations between 2009 and 2010. Participants were categorized into non-SLD (reference), MASLD, and MetALD groups and followed up until dementia onset, death, or December 31, 2019. SLD was defined by a fatty liver index ≥ 30, with (i) MASLD based on cardiometabolic risk factors, and (ii) MetALD as MASLD with moderate alcohol intake. Outcomes included overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Subdistribution hazard ratios (SHRs) was calculated using the Fine-Gray model, treating death as a competing risk.

RESULTS

Over 7,430,253 person-years of follow-up, 11,345 dementia cases occurred (10,863 AD and 2,159 VaD). Adjusted SHRs for MASLD were 1.10 (1.07-1.13) for AD and 1.20 (1.13-1.27) for VaD. For MetALD, SHRs were 0.90 (0.87-0.94) for AD and 1.53 (1.40-1.66) for VaD. Dementia risk in both MASLD and MetALD increased over longer periods, with MetALD initially linked to increased VaD risk and decreased AD risk, which reversed after three years.

CONCLUSIONS

MASLD and MetALD were associated with increased risks of AD and VaD; MetALD showing a stronger association with VaD. Understanding the distinct effects of different SLD subtypes on dementia is crucial for improving risk assessment and management strategies.