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

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.

Author information

1
Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
2
Atherosclerosis Research Unit, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
3
23andMe, Mountain View, CA.
4
Department of Pharmacology and Pharmaceutical Science, School of Pharmacy, University of Southern California, Los Angeles, CA.
5
Departments of Health Research and Policy (Epidemiology), and Neurology and Neurosciences, Stanford University, Stanford, CA.
6
Departments of Pharmacology & Neurology, College of Medicine, Center for Innovation in Brain Science, University of Arizona, Tucson, AZ.
7
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA.

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.

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