MASLD and MetALD may increase risks of Alzheimer's and vascular dementia: BMC

A new study published in the journal of BMC Gastroenterology showed that dementia risk was higher in patients with metabolic alcohol-associated liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD).

The following mechanisms may contribute to the development of dementia: increased insulin resistance in the brain, which causes oxidative stress, excessive free fatty acids, and mitochondrial dysfunction; and inflammation caused by liver fat, which activates microglial cells and increases the expression of inflammatory cytokines in the brain. There is mounting evidence linking MASLD to structural brain changes. Thus, this study sought to examine the relationship between MASLD and MetALD and the onset of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD), in this sizable group of elderly Koreans, in comparison to those without steatosis liver disease (SLD).

A total of 2,96,001 people over 60 who had health exams between 2009 and 2010 were included in this retrospective cohort research. The participants were tracked until dementia onset, death, or December 31, 2019, and were divided into three groups: non-SLD (reference), MASLD, and MetALD.

A fatty liver index of 30 or above was considered SLD, whereas (i) MASLD was determined by cardiometabolic risk factors, and (ii) MetALD was defined as MASLD with moderate alcohol use. The results included VaD, Alzheimer's disease (AD), and general dementia. The Fine-Gray model was used to compute subdistribution hazard ratios (SHRs), which treated mortality as a competing risk.

There were 11,345 instances of dementia during 74,30,253 person-years of follow-up (10,863 AD and 2,159 VaD). For MASLD, the adjusted SHRs were 1.20 (1.13–1.27) for VaD and 1.10 (1.07–1.13) for AD.

SHRs for MetALD were 1.53 (1.40–1.66) for VaD and 0.90 (0.87–0.94) for AD. Both MASLD and MetALD had higher dementia risk over longer time periods; initially, MetALD was associated with higher VaD risk and lower AD risk, but this relationship flipped after three years.

Overall, in relation to the study's findings, diagnosing SLD patients according to their metabolic complexity, hepatic steatosis, and alcohol intake may help to clarify how these factors relate to the risk of incident dementia and its subtypes, possibly providing different approaches to preventing dementia in both the MASLD and MetALD groups.

Reference:

Shin, W.-Y., Kang, E. S., Oh, Y. H., Sha, M., Xia, Q., Jeong, S., & Cho, Y. (2025). Metabolic dysfunction-associated steatotic liver disease, metabolic alcohol-related liver disease, and incident dementia: a nationwide cohort study : MASLD, MetALD, and dementia risk: MASLD, MetALD, and dementia risk. BMC Gastroenterology, 25(1), 308. https://doi.org/10.1186/s12876-025-03814-1