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Interactions Between Blood Nutritional Biomarkers and Apolipoprotein E ε4 in the Progression of Mild Cognitive Impairment in Alzheimer's Disease.

  • 2026-04-16
  • Nutrients 18(8)
    • Rasheedat Lawal
    • Sanjay Kumar
    • Rosemary Chigevenga
    • Shelly Coe

Study Design

Type
Systematic Review
Population
adults aged ≥55 years with MCI
Methods
Systematic review following PRISMA 2020 guidelines; narrative synthesis of seven studies (three longitudinal, two randomised controlled trials, two cross-sectional); assessed plasma/serum concentrations of vitamins A, D, E, B group, lipids, selenium, and ketogenic medium-chain triglycerides; genetic risk via APOE ε4 status; risk of bias assessed using RoB 2 and ROBINS-I; certainty of evidence using GRADE
  • Rigorous Journal

Background/objectives

Mild cognitive impairment (MCI), the prodromal stage of Alzheimer's disease, may be influenced by nutritional status and genetic susceptibility. This systematic review synthesised evidence on how nutritional biomarkers interact with genetic variants, particularly APOE ε4, to influence cognitive outcomes in individuals with MCI.

Methods

Following PRISMA 2020 guidelines, seven studies were included (three longitudinal, two randomised controlled trials, and two cross-sectional) involving adults aged ≥55 years with MCI. Nutritional exposures comprised plasma or serum concentrations of vitamins A, D, E, the vitamin B group, lipids, selenium, and ketogenic medium-chain triglycerides. Genetic risk was assessed primarily through APOE ε4 status. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Due to heterogeneity in biomarkers, cognitive tools, and study designs, findings were synthesised narratively.

Results

Across nutrient categories, higher concentrations of vitamin D, selenium, and antioxidants were associated with better cognitive outcomes. kMCT supplementation improved episodic memory and brain energy metabolism. Evidence for nutrient-gene interactions was mixed: APOE ε4 modified responses to vitamin B group and selenium but showed limited influence on vitamin D, lipids, or kMCT effects. Heterogeneity in biomarker assays, cognitive tools, and genetic stratification limited comparability across studies.

Conclusions

Nutritional biomarkers appear to influence cognitive trajectories in MCI, and some associations may differ by APOE ε4 status. However, small samples and limited genetic stratification constrain interpretation. Future research should prioritise standardised biomarker measurement, genetically stratified cohorts, and individual participant data meta-analyses to clarify nutrient-gene interactions in MCI.

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