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.

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.