The Influence of Metabolic Dysfunction-Associated Steatotic Liver Disease and Body Mass Index on the Incidence of Alzheimer Disease: A Nationwide Cohort Study.

Background/aims: This study aimed to investigate the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) and body mass index (BMI) on the incidence of Alzheimer disease (AD) in the general South Korean population.

Methods: The National Screening Program for Transitional Ages collected data from 66-year-old dementia-free Koreans in 2010 and 2011. MASLD was diagnosed based on the fatty liver index (≥30) and the presence of metabolic components, and overweight/obese status was defined as a BMI ≥23 kg/m². The primary outcome was the development of AD up to December 2021. Multivariable Cox analyses were performed to evaluate whether the presence of MASLD or overweight/obese status influenced the risk of developing AD.

Results: A total of 376,902 dementia-free individuals aged 66 years were included in this cohort. The participants were categorized into four groups: overweight/obese non-MASLD (30.4%, n=114,528), overweight/obese MASLD (37.0%, n=139,551), lean non-MASLD (29.9%, n=126,692), and lean MASLD (2.7%, n=10,131). During a mean follow-up period of 10.38±1.90 years, 23,874 individuals (6.3%) were newly diagnosed with AD. Compared to the overweight/obese non-MASLD group, the adjusted hazard ratios (95% confidence interval) for AD in the lean MASLD, lean non-MASLD, and overweight/obese MASLD groups were 1.34 (1.24 to 1.45), 1.08 (1.04 to 1.13), and 1.13 (1.09 to 1.17), respectively.

Conclusions: A normal/underweight BMI and the presence of MASLD synergistically increased the risk of AD. The lean MASLD group had a higher risk of developing AD than the overweight/obese MASLD group, suggesting that the clinical relevance of MASLD for incident AD differs based on the BMI.