Higher plasma omega-6 fatty acids are associated with lower dementia risk: evidence from NMR metabolomics and Alzheimer's disease polygenic risk in the UK Biobank
Abstract
BACKGROUND: Circulating polyunsaturated fatty acids (PUFAs) have been implicated in neurodegenerative processes, yet epidemiological evidence remains inconsistent. Genetic susceptibility to Alzheimer's disease (AD), commonly indexed by a polygenic risk score (PRS), is a major determinant of dementia risk. However, few large-scale prospective studies have jointly examined plasma fatty acid profiles and genetic liability to AD in relation to incident dementia.
OBJECTIVES: To investigate the independent and combined associations of plasma omega-3 PUFAs, omega-6 PUFAs, and the omega-6/omega-3 ratio with incident dementia, and to determine whether these associations vary according to AD-PRS.
METHODS: We analyzed data from 81,827 UK Biobank participants with baseline nuclear magnetic resonance (NMR) metabolomics and genetic information. Plasma fatty acids were quantified using standardized NMR spectroscopy, and genetic risk for AD was assessed using the Enhanced AD-PRS. Incident dementia was identified through linked hospital admission and death registry records. Multivariable-adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models. Dose-response relationships and both additive and multiplicative interactions with AD-PRS were evaluated, alongside subgroup and sensitivity analyses.
RESULTS: Over a median follow-up of 12.1 years, 1,335 participants developed dementia. Higher plasma omega-6 concentrations were consistently associated with a lower risk of…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 81,827 participants or records.
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