New research shows a significant link between accelerated brain aging and metabolic dysfunction-associated steatotic liver disease (MASLD), regardless of age and apolipoprotein E4 (APOE ɛ4) carrier status, which has been associated with elevated risk for Alzheimer’s disease.
For the study, recently published in Liver International, researchers reviewed data (including brain MRI scans) for 19,351 participants with no MASLD/related steatotic liver disease (SLD) and 7,360 participants with MASLD/related SLD. They also assessed brain aging with different subtypes of MASLD/related SLD, including MASLD (5,227 participants), MASLD with increased alcohol intake (MetALD) (2,104 participants) and MASLD with other combined etiologies (29 participants), according to the study.
The study authors found that people with MASLD/associated SLD had a brain age that was 1.07 years older than chronological age in contrast to 0.19 years older for study participants with no MASLD/associated SLD. More specifically, the brain age for participants with MASLD was 0.75 years older than chronological age and those with MetALD had a brain age that was 1.87 years older, according to the researchers.
Even after subsequent stratification by factors such as age and APOE ɛ4 carrier status, the researchers continued to see consistent associations between MASLD/related SLD, MASLD and MetALD, and brain aging.
“The present study provides evidence that MASLD/related SLD (including MASLD and MetALD) may contribute to accelerated brain aging, even in middle-aged adults and APOE ɛ4 non-carriers,” wrote lead study author Jiao Wang, M.D., who is affiliated with the Center of Gerontology and Geriatrics and the National Clinical Research Center for Geriatrics at West China Hospital and Sichuan University in Chengdu, China, and colleagues.
For study participants with MetALD < 60 years of age, the study authors found that the brain age gap (BAG) was 1.8 years in contrast to 1.13 years for participants > 60 years of age.
“Notably, our results showed that people with MetALD had a significantly larger BAG than other subtypes of MASLD/related SLD, which might be attributed to the detrimental impacts of excessive alcohol consumption on the brain. Heavy alcohol consumption has been associated with brain atrophy, loss of neurons and decline in white matter (fiber) integrity, and even moderate alcohol intake has an adverse association with global brain volume measures, regional grey matter volumes and white matter microstructure,” posited Wang and colleagues.
Three Key Takeaways
1. MASLD and accelerated brain aging. Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), including its subtype MetALD, exhibit significantly accelerated brain aging, even in middle-aged adults and those without the apolipoprotein E4 (APOE ɛ4) allele.
2. MetALD shows greatest brain aging effect. Among MASLD subtypes, MetALD (associated with alcohol intake) shows the largest brain age gap (BAG), suggesting alcohol’s compounding neurotoxic effects on brain structure and aging.
3. Inflammation as a modifiable target, Approximately 13.5 percent of the MASLD–brain aging link may be preventable by addressing low-grade systemic inflammation, highlighting a potential intervention point for mitigating brain aging risk.
The study authors also suggested that appropriate interventions to target low-grade inflammation (INFLA) may have a significant proactive impact in reducing accelerated brain aging with MASLD.
“Our study findings identified that about 13.53% of the MASLD-brain (aging) association may be potentially prevented by addressing the low-grade systemic inflammation,” added Wang and colleagues.
(Editor’s note: For related content, see “Skeletal Muscle Loss and Dementia: What Emerging MRI Research Reveals,” “New PET and MRI Research Suggests that Visceral Fat Reduction May Prevent or Delay Alzheimer’s Disease” and “Can Photon-Counting CT Facilitate a Viable Alternative to MRI for Liver Fat Quantification in Patients with MASLD?”)
In regard to study limitations, the authors noted possible underestimation of the association between MASLD, and brain imaging given that the cohort was comprised of volunteers who had no chronic brain disorders. The researchers also noted a lack of neuroimaging at baseline prohibited longitudinal evaluation of the trajectory between MASLD and brain aging.
