Research Question:
Does adherence to a healthy diet and favorable metabolic profiles influence long-term cognitive decline in stroke survivors? We aim to determine whether diet quality and metabolic control are associated with post-stroke cognitive trajectories, and whether blood biomarkers mediate these effects.
Objectives:
(1) Quantify longitudinal associations between diet (e.g., Healthy Diet Score, MIND adherence), glycemic markers (HbA1c), lipids (LDL-C, HDL-C, triglycerides), and cognitive function in stroke survivors;
(2) Assess whether traditional biomarkers (glucose, lipids) and metabolomic profiles (e.g., branched-chain amino acids, fatty acids) mediate the diet-cognition relationship;
(3) Evaluate causal effects of dietary and metabolic traits on cognition using Mendelian Randomization (MR), with genetic instruments from GWAS. Prior MR suggests genetically lower HDL-C increases dementia risk (OR!2.15).
Scientific Rationale:
Stroke increases dementia risk, but modifiable factors remain unclear. Emerging UK Biobank evidence shows healthy lifestyles reduce cognitive decline risk, potentially via improved metabolic signatures. The UKB cohort provides repeat cognitive measures, dietary data, biomarkers, and genetic and metabolomic (NMR lipidomics) profiles, uniquely enabling mechanistic analyses. Advanced metabolic traits may better capture biological pathways than traditional measures. By integrating longitudinal modeling, mediation (including metabolomics), and MR, this study will reveal actionable targets for cognitive protection in stroke survivors.