Volume 10, Issue 6 p. 666-674
Featured Article

An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease

Jessica B. Langbaum

Corresponding Author

Jessica B. Langbaum

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

Corresponding author. Tel.: 602-839-2548; Fax: 602-839-6936.

E-mail address: [email protected]

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Suzanne B. Hendrix

Suzanne B. Hendrix

Pentara Corporation, Salt Lake City, UT, USA

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Napatkamon Ayutyanont

Napatkamon Ayutyanont

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

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Kewei Chen

Kewei Chen

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

Department of Mathematics and Statistics, Arizona State University, Tempe, AZ, USA

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Adam S. Fleisher

Adam S. Fleisher

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

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Raj C. Shah

Raj C. Shah

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA

Department of Family Medicine, Rush University Medical Center, Chicago, IL, USA

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Lisa L. Barnes

Lisa L. Barnes

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA

Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA

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David A. Bennett

David A. Bennett

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA

Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

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Pierre N. Tariot

Pierre N. Tariot

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

Department of Psychiatry, University of Arizona, Tucson, AZ, USA

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Eric M. Reiman

Eric M. Reiman

Banner Alzheimer's Institute, Phoenix, AZ, USA

Arizona Alzheimer's Consortium, Phoenix, AZ, USA

Department of Psychiatry, University of Arizona, Tucson, AZ, USA

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA

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First published: 21 April 2014
Citations: 89

Abstract

Background

There is growing interest in the evaluation of preclinical Alzheimer's disease (AD) treatments. As a result, there is a need to identify a cognitive composite that is sensitive to track preclinical AD decline to be used as a primary endpoint in treatment trials.

Methods

Longitudinal data from initially cognitively normal, 70- to 85-year-old participants in three cohort studies of aging and dementia from the Rush Alzheimer's Disease Center were examined to empirically define a composite cognitive endpoint that is sensitive to detect and track cognitive decline before the onset of cognitive impairment. The mean-to-standard deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of cognitive tests/subtests drawn from the neuropsychological battery in cognitively normal participants who subsequently progressed to clinical stages of AD during 2- and 5-year periods, using data from those who remained unimpaired during the same period to correct for aging and practice effects. Combinations that performed well were then evaluated for representation of relevant cognitive domains, robustness across individual years before diagnosis, and occurrence of selected items within top performing combinations.

Results

The optimal composite cognitive test score comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the most sensitive individual test score was Logical Memory Delayed Recall with an MSDR = 0.64.

Conclusions

We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD.