Increased risk of Alzheimer’s Disease-associated mortality in non-obese vs. obese Metabolic dysfunction Associated Steatotic Liver Disease: a 30-year national cohort study

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized for its extrahepatic consequences, including emerging links to neurodegenerative disorders such as Alzheimer disease (AD). Whether AD mortality risk differs across MASLD phenotypes, remains unclear. Methods: We analyzed adults from the Third National Health and Nutrition Examination Survey (1988-1994) with mortality follow-up through 2019 via the National Death Index. Participants were followed for AD mortality. Cumulative incidence was estimated using Kaplan-Meier methods. Cox proportional hazards models evaluated MASLD phenotypes and AD mortality, adjusting for age, sex, race/ethnicity, poverty-income ratio, body mass index, and smoking status. Results: = .034). Conclusion: Nonobese MASLD emerged as distinct high-risk metabolic phenotype associated with significantly higher AD mortality, independent of demographic, socioeconomic, and behavioral factors. These findings suggest that nonobese MASLD may reflect unique neuro-metabolic vulnerability and warrant further mechanistic investigation into pathways such as differential adiposity patterns, inflammation, and metabolic signaling. Targeted screening, improved risk stratification, and prospective studies are needed to better define and mitigate long-term cognitive risks in this understudied subgroup.