Cardiorespiratory fitness and brain atrophy in early Alzheimer disease
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Abstract
Objective: To examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer disease (AD).
Background: In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known.
Methods: Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO2peak), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance.
Results: Cardiorespiratory fitness (VO2peak) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO2peak was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO2peak was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age.
Conclusions: Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.
GLOSSARY: AD = Alzheimer disease; CDR = Clinical Dementia Rating; MMSE = Mini-Mental State Examination; PASE = Physical Activity Scale in the Elderly.
Footnotes
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jburns2{at}kumc.edu
Supported by grants R03AG026374 and R21 AG029615 from the National Institutes of Aging and K23NS058252 from the National Institute on Neurological Disorders and Stroke and by support from the University of Kansas Endowment Association and the Fraternal Order of Eagles. The University of Kansas General Clinical Research Center (M01RR023940) provided essential space, expertise, and nursing support. The Hoglund Brain Imaging Center is supported by grant C76 HF00201 and Dr. Brooks is supported by NS039123 and AG026482. This study utilized the LONI Pipeline environment (http://pipeline.loni.ucla.edu), which was developed by the Laboratory of Neuro Imaging and partially funded by NIH grants P41 RR013642, R01 MH71940, and U54 RR021813. Also supported by Hal Oppenheimer and the Oppenheimer Foundation.
Disclosure: Dr. Burns has received honoraria for speaking from Pfizer and Novartis and as a consultant from Pfizer. Dr. Swerdlow has received honoraria from Forest, Eisai, Pfizer, and Ortho-McNeil for speaking. There are no disclosures from the other investigators.
Received December 5, 2007. Accepted in final form March 31, 2008.
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