Current studentsExisting staffContact us
 

Dementia risk across distinct metabolic profiles in the UK Biobank

Simple item page
dc.contributor.authorLumsden, A.L.
dc.contributor.authorMulugeta, A.
dc.contributor.authorHypponen, E.
dc.date.issued2025
dc.description.abstractSub-optimal metabolism is linked to dementia risk, yet metabolic traits rarely occur in isolation. Using data from 308,019 UK Biobank participants, we examined associations of six diverse metabolic subgroups (I-VI) - previously derived via a self-organising map (SOM) that captures patterns of co-occurring metabolic biomarker traits in the population - and 39 individual biomarkers, with incident all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Biomarker associations were assessed using both linear and nonlinear (restricted cubic spline) models. After adjusting for age, sex, socioeconomic, and lifestyle factors, subgroup analyses showed that participants in the two leanest and two most adipose subgroups had higher risk of dementia outcomes compared to others. Subgroups with high adiposity exhibited elevated VaD risk, which was linked to hypertension, hyperglycaemia, and liver stress (Subgroup II); inflammation, microalbuminuria, and low apolipoprotein A1 (III). For AD, the risk was elevated in the lean subgroups (IV, V), characterised by low body mass index (BMI), triglycerides, and urate, and high sex-hormone binding globulin; as well as for adipose Subgroup II. APOE-epsilon 4 allele count had limited influence on dementia associations with metabolic subgroups and biomarkers. This marked metabolic heterogeneity in dementia risk suggests that metabolic profiling could inform targeted prevention strategies. Interpretation of these findings is supported by previously reported MRI profiles of the metabolic subgroups, providing biological context.
dc.identifier.citationGeroScience, online, 2025; online:1-25
dc.identifier.doi10.1007/s11357-025-01970-6
dc.identifier.issn2509-2715
dc.identifier.issn2509-2723
dc.identifier.orcidHypponen, E. [0000-0003-3670-9399]
dc.identifier.urihttps://hdl.handle.net/11541.2/45433
dc.language.isoen
dc.publisherSpringer Charm
dc.relation.fundingMedical Research Future Fund (AU) MRF2007431
dc.relation.fundingNHMRC 2025349
dc.relation.fundingNHMRC 1157281
dc.relation.fundingUniversity of South Australia
dc.rightsCopyright 2025
dc.source.urihttps://doi.org/10.1007/s11357-025-01970-6
dc.subjectBiomarkers
dc.subjectDementia risk
dc.subjectMetabolic profile
dc.subjectMetabolic subgroup
dc.subjectSelf-organising map
dc.titleDementia risk across distinct metabolic profiles in the UK Biobank
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9917087544601831

Files

Collections