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Neuropathological Associates of Multiple Cognitive Functions in Two Community-Based Cohorts of Older Adults

Published online by Cambridge University Press:  22 November 2010

N. Maritza Dowling ,
Sarah Tomaszewski Farias ,
Bruce R. Reed ,
Joshua A. Sonnen ,
Milton E. Strauss ,
Julie A. Schneider ,
David A. Bennett  and
Dan Mungas
N. Maritza Dowling*
Affiliation:
Department of Biostatistics & Medical Informatics, School of Medicine & Public Health, University of Wisconsin, Madison, Wisconsin
Sarah Tomaszewski Farias
Affiliation:
Department of Neurology, School of Medicine, University of California, Davis, California
Bruce R. Reed
Affiliation:
Department of Neurology, School of Medicine, University of California, Davis, California Veterans Administration Northern California Health Care System, Martinez, California
Joshua A. Sonnen
Affiliation:
Department of Pathology, University of Washington, Seattle, Washington
Milton E. Strauss
Affiliation:
Case Western Reserve University, Cleveland, Ohio
Julie A. Schneider
Affiliation:
Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois
David A. Bennett
Affiliation:
Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois
Dan Mungas
Affiliation:
Department of Neurology, School of Medicine, University of California, Davis, California
*
Correspondence and reprint requests to: N. Maritza Dowling, PhD, Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison, School of Medicine and Public Health, K6/446 – Box 4675, Clinical Science Center, J5/M194, 600 Highland Avenue, Madison, WI 53792-4675. E-mail: nmdowlin@biostat.wisc.edu
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Abstract

Studies of neuropathology-cognition associations are not common and have been limited by small sample sizes, long intervals between autopsy and cognitive testing, and lack of breadth of neuropathology and cognition variables. This study examined domain-specific effects of common neuropathologies on cognition using data (N = 652) from two large cohort studies of older adults. We first identified dimensions of a battery of 17 neuropsychological tests, and regional measures of Alzheimer’s disease (AD) neuropathology. We then evaluated how cognitive factors were related to dimensions of AD and additional measures of cerebrovascular and Lewy Body disease, and also examined independent effects of brain weight. All cognitive domains had multiple neuropathology determinants that differed by domain. Neocortical neurofibrillary tangles were the strongest predictors of most domains, while medial temporal tangles showed a weaker relationship with episodic memory. Neuritic plaques had relatively strong effects on multiple domains. Lewy bodies and macroscopic infarcts were associated with all domains, while microscopic infarcts had more limited associations. Brain weight was related to all domains independent of specific neuropathologies. Results show that cognition is complexly determined by multiple disease substrates. Neuropathological variables and brain weight contributed approximately a third to half of the explained variance in different cognitive domains. (JINS, 2011, 17, 602–614).

Keywords

Latent variable analysisConfirmatory factor analysisNeuropathologyMIMICCerebrovascular diseaseNeuropsychological test battery
Type
Special Series
Information
Journal of the International Neuropsychological Society , Volume 17 , Issue 4 , 21 June 2011 , pp. 602 - 614
Copyright
Copyright © The International Neuropsychological Society 2010

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