PloS one · 2026
Metabolic risk and metabolic dysfunction-associated steatotic liver disease and steatohepatitis in cognitive decline: A retrospective cohort study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Nasir Ahmad Basil, Kilani Yassine, Aldiabat Mohammad, Abdelghany Omar, Hafez Youssef, Desai Nitin, Madi Mahmoud Y, Wade Francis G, Qureshi Kamran, Frey Lewis J, Farmer Adam D, Syn Wing-Kin
Аннотация
OBJECTIVE: To determine whether metabolic risk factors (MRFs), metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are associated with incident mild cognitive impairment (MCI), vascular dementia (VD), and Alzheimer disease (AD).
DESIGN: Retrospective cohort study using TriNetX (2003-2023) with Propensity score matching.
SETTING: Multicenter, population-based sample from 69 U.S. healthcare organizations in the TriNetX electronic health record.
PARTICIPANTS: Adults aged ≥50 years with ≥1 outpatient visit and sufficient clinical/laboratory data. Individuals with prior diagnoses of cognitive impairment, cerebrovascular disease, advanced liver disease, malignancy, schizophrenia, or substance use disorders were excluded. Two matched cohorts were constructed: one with 3,546,833 individuals with MRFs and 3,546,833 healthy controls, and another with 525,844 individuals with MASLD/MASH and 525,844 with MRFs only. Matching was based on age, sex, race, and ethnicity.
PRIMARY AND SECONDARY OUTCOME MEASURES: Incident MCI, VD, and AD, identified using ICD-10 codes, assessed at 5-20-year intervals. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Outcomes were prespecified.
RESULTS: Among 7,818,146 participants (mean [SD] age, 64.9 [8.8] years; 52.0% female), individuals with MRFs had higher odds of VD (OR, 1.65; 95% CI, 1.63-1.67), MCI (OR, 1.45; 95% CI, 1.42-1.48), and AD (OR, 1.21; 95% CI, 1.19-1.24) vs healthy controls. Compared to the MRF group, individuals with MASLD/MASH had lower odds of VD (OR, 0.86; 95% CI, 0.83-0.89) and AD (OR, 0.83; 95% CI, 0.78-0.88), but higher odds of MCI (OR, 1.37; 95% CI, 1.30-1.44); all p < .001.
CONCLUSIONS: In this large, propensity-matched retrospective cohort study, MRFs were independently associated with significantly increased long-term odds of MCI, VD, and AD. MASLD/MASH demonstrated a divergent cognitive risk profile relative to MRFs alone-characterized by higher odds of MCI but paradoxically lower odds of VD and AD, a pattern that warrants cautious interpretation given potential competing mortality risk, survivor bias, and residual confounding. These findings suggest that MASLD/MASH is associated with a distinct cognitive trajectory, highlighting the importance of early cognitive surveillance in this population.
DESIGN: Retrospective cohort study using TriNetX (2003-2023) with Propensity score matching.
SETTING: Multicenter, population-based sample from 69 U.S. healthcare organizations in the TriNetX electronic health record.
PARTICIPANTS: Adults aged ≥50 years with ≥1 outpatient visit and sufficient clinical/laboratory data. Individuals with prior diagnoses of cognitive impairment, cerebrovascular disease, advanced liver disease, malignancy, schizophrenia, or substance use disorders were excluded. Two matched cohorts were constructed: one with 3,546,833 individuals with MRFs and 3,546,833 healthy controls, and another with 525,844 individuals with MASLD/MASH and 525,844 with MRFs only. Matching was based on age, sex, race, and ethnicity.
PRIMARY AND SECONDARY OUTCOME MEASURES: Incident MCI, VD, and AD, identified using ICD-10 codes, assessed at 5-20-year intervals. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Outcomes were prespecified.
RESULTS: Among 7,818,146 participants (mean [SD] age, 64.9 [8.8] years; 52.0% female), individuals with MRFs had higher odds of VD (OR, 1.65; 95% CI, 1.63-1.67), MCI (OR, 1.45; 95% CI, 1.42-1.48), and AD (OR, 1.21; 95% CI, 1.19-1.24) vs healthy controls. Compared to the MRF group, individuals with MASLD/MASH had lower odds of VD (OR, 0.86; 95% CI, 0.83-0.89) and AD (OR, 0.83; 95% CI, 0.78-0.88), but higher odds of MCI (OR, 1.37; 95% CI, 1.30-1.44); all p < .001.
CONCLUSIONS: In this large, propensity-matched retrospective cohort study, MRFs were independently associated with significantly increased long-term odds of MCI, VD, and AD. MASLD/MASH demonstrated a divergent cognitive risk profile relative to MRFs alone-characterized by higher odds of MCI but paradoxically lower odds of VD and AD, a pattern that warrants cautious interpretation given potential competing mortality risk, survivor bias, and residual confounding. These findings suggest that MASLD/MASH is associated with a distinct cognitive trajectory, highlighting the importance of early cognitive surveillance in this population.