| Title: | Metabolomic ageing (MileAge) in mid-life predicts incident vascular, unspecified and all-cause dementia |
| Journal: | Alzheimer's & Dementia |
| Published: | 13 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42126002/ |
| DOI: | https://doi.org/10.1002/alz.71280 |
Publication 20065
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Abstract
INTRODUCTION: Identifying individuals at risk of dementia is essential for prevention and targeted disease-modifying strategies. We investigated whether mid-life metabolomic ageing is associated with incident dementia and its age of onset and assessed joint associations and interactions with APOE genotype and dementia polygenic scores.</p>
METHODS: In the UK Biobank, plasma metabolites were quantified at baseline. Metabolomic age (MileAge) delta reflects the difference between metabolite-predicted and chronological age. Dementia was identified via health records.</p>
RESULTS: Amongst 223,496 participants, 3976 developed dementia. A higher MileAge delta was associated with higher hazards of all-cause, unspecified and vascular dementia (HR = 1.61, 95% CI 1.28-2.02, p = 0.001) and earlier onset. Key metabolites were lipids, lipoproteins and amino acids. MileAge delta and genetic risk were jointly associated with dementia. Individuals with a high MileAge delta and two APOE ε4 alleles had a 10.30-fold higher all-cause dementia risk (95% CI 7.95-13.34, p < 0.001).</p>
DISCUSSION: Metabolomic ageing and genetic risk likely represent independent biological pathways contributing to dementia risk.</p>
14 Keywords
- Aged
- Aging
- Apolipoproteins E
- Dementia
- Dementia, Vascular
- Female
- Genotype
- Humans
- Incidence
- Male
- Metabolomics
- Middle Aged
- Risk Factors
- United Kingdom
5 Authors
- Julian Mutz
- Lachlan Gilchrist
- Oliver Pain
- Petroula Proitsi
- Cathryn M. Lewis
1 Application
| Application ID | Title |
|---|---|
| 45514 | Exploring predictors of healthy ageing in UK Biobank |
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