Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: Potential for detecting an at-Alzheimer's risk metabolic phenotype

Jamaica R. Rettberg, Ha Dang, Howard N. Hodis, Victor W. Henderson, Jan A. St. John, Wendy J. Mack, Roberta Diaz Brinton

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Detecting at-risk individuals within a healthy population is critical for preventing or delaying Alzheimer's disease. Systems biology integration of brain and body metabolism enables peripheral metabolic biomarkers to serve as reporters of brain bioenergetic status. Using clinical metabolic data derived from healthy postmenopausal women in the Early versus Late Intervention Trial with Estradiol (ELITE), we conducted principal components and k-means clustering analyses of 9 biomarkers to define metabolic phenotypes. Metabolic clusters were correlated with cognitive performance and analyzed for change over 5 years. Metabolic biomarkers at baseline generated 3 clusters, representing women with healthy, high blood pressure, and poor metabolic phenotypes. Compared with healthy women, poor metabolic women had significantly lower executive, global and memory cognitive performance. Hormone therapy provided metabolic benefit to women in high blood pressure and poor metabolic phenotypes. This panel of well-established clinical peripheral biomarkers represents an initial step toward developing an affordable, rapidly deployable, and clinically relevant strategy to detect an at-risk phenotype of late-onset Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalNeurobiology of Aging
Volume40
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Biomarker
  • Cognitive aging
  • Hormone therapy
  • Menopause
  • Metabolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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