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Cognitive and Physiologic Correlates of Subclinical Structural Brain Disease in Elderly Healthy Control Subjects
Ian A. Cook, MD;
Andrew F. Leuchter, MD;
Melinda L. Morgan, PhD;
Elise Witte Conlee, PhD;
Steven David;
Robert Lufkin, MD;
Ashkan Babaie, MD;
Jennifer J. Dunkin, PhD;
Ruth O'Hara, PhD;
Sara Simon, PhD;
Amy Lightner, MD;
Susan Thomas, MD;
David Broumandi, MD;
Neeraj Badjatia, MD;
Laura Mickes;
Rajal K. Mody, MD;
Sanjaya Arora, MD;
Zimu Zheng, MD;
Michelle Abrams, RN;
Susan Rosenberg-Thompson, MSN
Arch Neurol. 2002;59:1612-1620.
Context Healthy elderly persons commonly show 4 types of change in brain structure—cortical
atrophy, central atrophy, deep white-matter hyperintensities, and periventricular
hyperintensities—as forms of subclinical structural brain disease (SSBD).
Objectives To characterize the volumes of SSBD present with aging and to determine
the associations of SSBD, physiology, and cognitive function.
Design Cross-sectional study.
Setting University of California, Los Angeles, Neuropsychiatric Institute.
Subjects Forty-three community-dwelling healthy control subjects, aged 60 through
93 years.
Main Outcome Measures Volumetric magnetic resonance imaging, neuropsychological testing, and
quantitative electroencephalographic coherence (functional connectivity) between
brain regions.
Results Regression models demonstrated significant relationships between SSBD
volumes, age, cognitive performance, and connectivity. Cortical and central
atrophy and periventricular hyperintensities had significant associations
with age while deep white-matter hyperintensities did not. Posterior atrophy
showed stronger associations with age than did anterior atrophy. Only a subset
of subjects at older ages showed large SSBD volumes; older subjects primarily
showed increasing variance of SSBD. Although all subjects scored within the
normal range on cognitive testing, SSBD volume was inversely related to performance,
most notably on the Trail-Making Test part B and the Shipley-Hartford Abstract
Reasoning test. Coherence had significant associations with SSBD. Path analysis
supported mediation of the effects of deep white-matter hyperintensities and
periventricular hyperintensities on cognition by altered connectivity. For
several measures, cognitive performance was best explained by coherence, and
only secondarily by SSBD.
Conclusions Modest volumes of SSBD were associated with decrements in cognitive
performance within the normal range in healthy subjects. Lower coherence was
associated with greater volumes of SSBD and increasing age. Path analysis
models suggest that brain functional connectivity mediates some effects of
SSBD on cognition.
From the University of California, Los Angeles, Neuropsychiatric Institute
and the University of California, Los Angeles, School of Medicine.
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