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Amyloid Burden, Neuronal Function, and Cognitive Decline in Middle-Aged Adults at Risk for Alzheimer's Disease

Published online by Cambridge University Press:  11 March 2014

Ozioma C. Okonkwo ,
Jennifer M. Oh ,
Rebecca Koscik ,
Erin Jonaitis ,
Caitlin A. Cleary ,
N. Maritza Dowling ,
Barbara B. Bendlin ,
Asenath LaRue ,
Bruce P. Hermann  and
Todd E. Barnhart
...Show all authors
Ozioma C. Okonkwo*
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Jennifer M. Oh
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Rebecca Koscik
Affiliation:
Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Erin Jonaitis
Affiliation:
Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Caitlin A. Cleary
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
N. Maritza Dowling
Affiliation:
Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Biostatistics & Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Barbara B. Bendlin
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Asenath LaRue
Affiliation:
Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Bruce P. Hermann
Affiliation:
Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Todd E. Barnhart
Affiliation:
Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Dhanabalan Murali
Affiliation:
Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Howard A. Rowley
Affiliation:
Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Cynthia M. Carlsson
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Catherine L. Gallagher
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Sanjay Asthana
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Mark A. Sager
Affiliation:
Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Brad T. Christian
Affiliation:
Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Sterling C. Johnson
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
*
Correspondence and reprint requests to: Ozioma C. Okonkwo, Department of Medicine and Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792. E-mail: ozioma@medicine.wisc.edu.
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Abstract

The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed. (JINS, 2014, 20, 1–12)

Keywords

Longitudinal cognitive declineAmyloidFDGfMRIFamily history of ADPreclinical AD
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 20 , Issue 4 , April 2014 , pp. 422 - 433
Copyright
Copyright © The International Neuropsychological Society 2014 

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