Hepatic dysfunction and long-term risk of neurodegenerative diseases: A UK Biobank-based analysis.
Large UK Biobank analysis links multiple liver health measures to risk of several neurodegenerative diseases, with strong associations for vascular and all-cause dementias but only modest, limited associations (3 factors) for Parkinson's disease.
What the AI sees
Large UK Biobank analysis links multiple liver health measures to risk of several neurodegenerative diseases, with strong associations for vascular and all-cause dementias but only modest, limited associations (3 factors) for Parkinson's disease.
Research significance
The study supplies population-level evidence that liver dysfunction modestly correlates with PD risk and highlights liver-related biomarkers that merit mechanistic and translational follow-up, but it is observational and does not provide causal pathways or immediate therapeutic targets for…
Source abstract
OBJECTIVE: Neurodegenerative diseases (NDDs) are incurable disorders with diverse etiologies; emerging evidence links liver health to NDDs' risk, yet no clinical systematic investigation exists. METHODS: We examined liver health (assessed via 6 blood biochemistry, 21 hepatokines, 2 imaging markers, 8 liver diseases) and its link to NDDs. The NDDs encompassed Alzheimer's disease (AD), frontotemporal dementia (FTD), unspecified dementia, vascular dementia (VaD), all-cause dementia (ACD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), all-cause parkinsonism, dystonia (DYT), and motor neuron disease (MND). Cox regression analysis was employed across four models, and distinct discriminative models were further constructed for each NDDs. RESULTS: Analysis of 502,163 participants in the UK Biobank revealed disease-specific associations between the liver health and NDDs. The highest number of significant liver-related factors, across at least three analysis models, was observed for VaD with 13 factors, followed by ACD with 10 factors, unspecified dementia with 9 factors, and AD with 7 factors. For non-dementia related NDDs, fewer associations were detected: 3 factors for PD, 3 for all-cause parkinsonism, 2 for DYT, and single factors for MSA, PSP, and MND. Ten significant-liver-factor-based models (beyond FTD) demonstrated a strong discriminative ability for NDDs incidence, especially dementia-related outcomes. The 5-year and 10-year AUC values were as follows: 0.781/0.834 for AD; 0.907/0.888 for VaD; 0.799/0.857 for unspecified dementia; 0.808/0.834 for ACD. CONCLUSION: These findings firmly establish liver health as a potential target for the evaluation of NDDs' risk and our results suggest that interventions designed to safeguard liver might represent a preventive strategy against neurodegeneration.