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In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
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In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease

Published on: July 19, 2024

Metabolic risk and metabolic dysfunction-associated steatotic liver disease and steatohepatitis in cognitive decline:

Ahmad Basil Nasir1, Yassine Kilani2, Mohammad Aldiabat3

  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.

Plos One
|July 9, 2026
PubMed
Abstract

Insights

Metabolic risk factors (MRFs) significantly increase the odds of cognitive decline, including mild cognitive impairment (MCI), vascular dementia (VD), and Alzheimer disease (AD). Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) show a different pattern, with higher MCI odds but lower VD and AD odds.

Area of Science:

  • Neurology
  • Metabolic Disorders
  • Hepatology

Background:

  • Metabolic risk factors (MRFs) are increasingly recognized as contributors to neurological conditions.
  • Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) represent significant metabolic and hepatic comorbidities.
  • The precise relationship between MRFs, MASLD/MASH, and specific neurodegenerative diseases like mild cognitive impairment (MCI), vascular dementia (VD), and Alzheimer disease (AD) requires further elucidation.

Purpose of the Study:

  • To investigate the association between MRFs, MASLD/MASH, and the incidence of MCI, VD, and AD.
  • To compare the cognitive risk profiles associated with MRFs versus MASLD/MASH.

Main Methods:

  • A retrospective cohort study utilizing the TriNetX electronic health record network (2003-2023).
  • Propensity score matching was employed to create comparable cohorts of individuals with MRFs, MASLD/MASH, and healthy controls.
  • Large sample sizes (over 3.5 million per cohort) and a minimum follow-up of 5 years were used to assess incident cognitive outcomes based on ICD-10 codes.

Main Results:

  • Individuals with MRFs exhibited significantly higher odds of developing VD (OR 1.65), MCI (OR 1.45), and AD (OR 1.21) compared to healthy controls.
  • Compared to individuals with MRFs only, those with MASLD/MASH showed increased odds of MCI (OR 1.37) but paradoxically lower odds of VD (OR 0.86) and AD (OR 0.83).

Conclusions:

  • MRFs are independently linked to substantially increased long-term risks of MCI, VD, and AD.
  • MASLD/MASH presents a distinct cognitive risk profile compared to MRFs alone, characterized by elevated MCI risk but reduced VD and AD risk.
  • These findings underscore the need for cautious interpretation due to potential confounding factors and highlight the importance of cognitive surveillance in individuals with MASLD/MASH.

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