| Title: | Metabolic Vulnerability Indices and Alzheimer's Disease Risk: A Prospective Analysis of the UK Biobank Cohort |
| Journal: | Journal of Nutrition |
| Published: | 10 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42575373/ |
| DOI: | https://doi.org/10.1016/j.tjnut.2026.101777 |
Publication 21024
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Abstract
BACKGROUND: Metabolic dysfunction is implicated in Alzheimer's disease (AD) pathogenesis. Branched-chain amino acids have been prospectively linked to dementia risk, yet prospective associations of composite metabolic vulnerability indices with incident AD remain untested.</p>
OBJECTIVES: This study aimed to examine associations of the metabolic vulnerability index (MVX), inflammatory vulnerability index (IVX), and metabolic malnutrition index (MMX) with incident AD in the United Kingdom Biobank (UKB).</p>
METHODS: Among 367,715 UKB participants without dementia (mean age 56.93 y, 54.3% female; 2006-2010 baseline), incident AD was ascertained through hospital and death registry linkage. Fully adjusted Cox models (model 3) constituted the prespecified primary analysis; 3 Bonferroni-corrected tests (α = 0.0167) addressed multiple comparisons. Restricted cubic splines characterized the association shape; interaction analyses examined potential effect modification by sex, age group, diabetes status, body mass index, inflammatory status, and polygenic risk.</p>
RESULTS: Over 13.7 y, 2615 participants developed AD. Per 1-SD increase, MMX [hazard ratio (HR) = 1.16, 95% confidence interval (CI): 1.12, 1.21; P = 4.93 × 10-13] and MVX (HR = 1.12, 95% CI: 1.07, 1.17; P = 3.72 × 10-6) were each associated with higher AD risk, both meeting the Bonferroni-corrected threshold; IVX showed no association (P = 0.108). Associations were approximately linear and monotonically increasing. Sex-specific associations were observed for MMX (stronger in males, P-interaction = 0.004) and MVX (stronger in females, P-interaction = 0.003). Sensitivity analyses confirmed robustness.</p>
CONCLUSIONS: MMX and MVX are independently associated with incident AD, supporting the clinical relevance of metabolic health monitoring in neurodegeneration risk stratification.</p>
8 Authors
- Guanran Ding
- Yuting Liu
- Yixin Zhao
- Xinqiao Chen
- Yuwei He
- Yuguang Li
- Naifei Chen
- Jiuwei Cui
1 Application
| Application ID | Title |
|---|---|
| 176493 | Harnessing Multi-Omics and Multimodal Data to Decipher the Interplay Between Diet, Inflammation, Metabolic Dysregulation, and Progression of Chronic Diseases |
Enabling scientific discoveries that improve human health