title: 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.
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.
authors.affiliation: Neuroscience Department, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jamaica R
authors.initials: JR
authors.lastname: Rettberg
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ha
authors.initials: H
authors.lastname: Dang
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.affiliation: Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, CA, USA; Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Henderson
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jan A
authors.initials: JA
authors.lastname: St John
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.affiliation: Neuroscience Department, University of Southern California, Los Angeles, CA, USA; Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: rbrinton@usc.edu.
authors.forename: Roberta Diaz
authors.initials: RD
authors.lastname: Brinton
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D015415:Biomarkers; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D015331:Cohort Studies; D004958:Estradiol / Q000627:therapeutic use; D056344:Executive Function; D005260:Female; D006801:Humans; D008568:Memory; D008875:Middle Aged; D010641:Phenotype; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D015415:Biomarkers; D004958:Estradiol
keywords: Alzheimer's disease; Biomarker; Cognitive aging; Hormone therapy; Menopause; Metabolism