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

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. 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. 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. 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.