Apolipoprotein E4 genotype in combination with poor metabolic profile is associated with reduced cognitive performance in healthy postmenopausal women: implications for late onset Alzheimer's disease

Menopause. 2019 Jan;26(1):7-15. doi: 10.1097/GME.0000000000001160.


Objective: We hypothesized the association of metabolic profile on cognition in postmenopausal women will be greater among ApoE4 carriers compared with noncarriers.

Methods: Metabolic biomarkers and measures of global cognition, executive functions, and verbal memory, collected among postmenopausal females, were used in this analysis. Clustering analyses of metabolic biomarkers revealed three phenotypes: healthy, predominantly hypertensive, and poor metabolic with (borderline normal laboratory values). General linear models tested whether an association of metabolic cluster with cognition differed by ApoE4 genotype.

Results: In the total sample of 497 women, verbal memory was lower in the poor metabolic cluster (P = 0.04). Among ApoE4+ women, performance in all cognitive domains was lowest in the poor metabolic cluster. Differences in executive functions among metabolic clusters were detected only in ApoE4+ women (P value for interaction = 0.003).

Conclusions: In a general population of postmenopausal women, association between poor metabolic profile with reduction in cognitive performance is more apparent in women who carry an ApoE4 allele. These data indicate a window of opportunity for interventions to reverse the trajectory of the preclinical phase of Alzheimer's disease.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alleles
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / prevention & control
  • Apolipoprotein E4 / genetics*
  • Biomarkers / blood
  • Cognition / physiology*
  • Double-Blind Method
  • Executive Function
  • Female
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Humans
  • Memory
  • Metabolome / physiology*
  • Middle Aged
  • Neuropsychological Tests
  • Phenotype
  • Postmenopause / blood
  • Postmenopause / genetics*
  • Risk
  • Women's Health


  • Apolipoprotein E4
  • Biomarkers