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Molecular Neuropsychology: Creation of Test-Specific Blood Biomarker Algorithms

O'Bryant S.E.a · Xiao G.d · Barber R.c · Cullum C.M.e, g · Weiner M.e, f · Hall J.b · Edwards M.h · Grammas P.i · Wilhelmsen K.j · Doody R.k · Diaz-Arrastia R.l · Texas Alzheimer’s Research and Care Consortium
Departments of aInternal Medicine, bPsychiatry and cPharmacology and Neuroscience, and Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Tex., Departments of dClinical Sciences, ePsychiatry, fNeurology and Neurotherapeutics and gNeurology, University of Texas Southwestern Medical Center, Dallas, Tex., hDepartment of Psychology, University of North Texas, Denton, Tex., iTexas Tech University Health Sciences Center, Garrison Institute on Aging, Lubbock, Tex., jDepartment of Genetics, University of North Carolina School of Medicine, Chapel Hill, N.C., kDepartment of Neurology, Baylor College of Medicine, Houston, Tex., and lCenter for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Rockville, Md., USA Dement Geriatr Cogn Disord 2014;37:45-57 (DOI:10.1159/000345605)

Abstract

Background: Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance. Methods: A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients and 198 controls) from the Texas Alzheimer's Research and Care Consortium. Results: The biomarker risk scores were significant predictors (p < 0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores and demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms. Conclusions: Our findings provide proof of concept for a novel area of scientific discovery, which we term ‘molecular neuropsychology'.

 

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