Incident cognitive impairment in nonobese versus obese adults aged 50 years or older with metabolic dysfunction-associated steatotic liver disease: A propensity score-matched cohort study

Authors

• Akram Alnounou, Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA, wmich.edu.
• Mohammad Alabbas, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA, clevelandclinic.org.
• Riddhi Machchhar, Department of Medicine, Saint Peter's University Hospital/Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA, duhs.edu.pk.
• EzzEIDien A. Ibrahim, Department of Internal Medicine, University of Missouri-Columbia, Columbia, Missouri, USA, missouri.edu.
• Mohammad Alali, Department of Internal Medicine, Henry Ford Macomb Hospital, Clinton Township, Michigan, USA, henryford.com.
• Ahmad Alhusen, Advocate Health - MidwestFollow
• Syed-Mohammed Jafri, Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan, USA, henryford.com.
• Basile Njei, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA, yale.edu.

Recommended Citation

Alnounou A, Alabbas M, Machchhar R, et al. Incident Cognitive Impairment in Nonobese Versus Obese Adults Aged 50 Years or Older With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Propensity Score-Matched Cohort Study. Int J Hepatol. 2026;2026:7550224. Published 2026 Aug 26. doi:10.1155/ijh/7550224

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Aims: Nonobese metabolic dysfunction-associated steatotic liver disease (MASLD) may carry disproportionate neurodegenerative risk, but whether body habitus modifies cognitive risk within MASLD remains unresolved. We compared cognitive impairment between nonobese and obese adults aged 50 years or older with MASLD.

Methods and results: Retrospective cohort study with 1:1 propensity score matching in the TriNetX Research Network, a federated electronic health record network. Adults with a first MASLD diagnosis (2016-2022) meeting a metabolic-risk criterion were classified by index body mass index as nonobese (18.50-29.99 kg/m²) or obese (≥ 30.00 kg/m²); underweight patients were excluded. The primary outcome was a composite of incident cognitive impairment (mild cognitive impairment [MCI] through dementia) over Days 366-1825. Hazard ratios (HRs) were estimated with Kaplan-Meier and log-rank methods; a negative control (acute appendicitis) and an E-value assessed bias. Matching yielded 36,021 patients per group (mean age 64.3 years; 57% women; all standardized mean differences < 0.10). Nonobese MASLD was associated with a higher risk of the composite cognitive outcome (2.9% vs 2.6%; HR 1.126, 95% confidence interval [CI] 1.031-1.230; p = 0.008; E-value 1.50), driven by MCI (HR 1.221, 95% CI 1.078-1.384; p = 0.002). Estimates were null for incident Alzheimer disease, all-cause dementia, vascular dementia, all-cause mortality, and the negative control.

Conclusion: Among adults aged 50 years or older with MASLD, nonobese status was associated with a modestly higher risk of incident cognitive impairment. Prospective validation in imaging- or biomarker-confirmed MASLD cohorts is warranted.

Type

Article

PubMed ID

42657128