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.