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

Roksana Karim, Melissa Koc, Jamaica R. Rettberg, Howard N. Hodis, Victor W. Henderson, Jan A.S. John, Hooman Allayee, Roberta D. Brinton, Wendy J. Mack

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalMenopause
Volume26
Issue number1
DOIs
StatePublished - 2019

Keywords

  • Alzheimer disease
  • Biomarker
  • Cognitive impairment
  • Menopause
  • Metabolic profile

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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