A blood-based metabolomic “aging clock” developed from mid-life plasma samples was associated with increased risk of several dementia subtypes and earlier disease onset in a large UK Biobank study published in Alzheimer’s & Dementia.
Researchers analyzed data from 223,496 UK Biobank participants who underwent plasma metabolomic profiling at baseline. Over a median follow-up of 13.7 years, 3,976 individuals developed dementia.
The study used a metabolite-based biological aging measure called “MileAge,” which compares a person’s metabolite-predicted age with their chronological age. A higher “MileAge delta” indicated a biologically older metabolic profile. The model was built using 168 plasma metabolites measured by nuclear magnetic resonance (NMR), including lipids, lipoproteins, and amino acids.
Individuals with higher MileAge scores had increased risk of vascular dementia, unspecified dementia, and all-cause dementia.
Higher MileAge scores were also associated with earlier onset of dementia, including Alzheimer’s disease.
Several metabolite groups linked to the MileAge model were also associated with dementia risk. Lipids, lipoproteins, branched-chain amino acids, and inflammatory markers were among the key contributors. The inflammatory biomarker GlycA was associated with higher vascular dementia risk, while several lipid and lipoprotein markers were linked to lower dementia risk.
The investigators also examined how metabolomic aging interacts with genetic risk factors such as APOE genotype. Individuals with both elevated MileAge scores and two APOE ε4 alleles had more than a 10-fold higher risk of all-cause dementia compared with reference groups.
According to the authors, the findings suggest that the MileAge measure could help identify individuals at risk of dementia before symptom onset.
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