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Regional network of magnetic resonance imaging gray matter volume in healthy aging

Alexander, Gene E.a e; Chen, Keweib e; Merkley, Tricia L.a e; Reiman, Eric M.b c e; Caselli, Richard J.d e; Aschenbrenner, Melaneya e; Santerre-Lemmon, Lauraa e; Lewis, Diana J.a e; Pietrini, Pietroh; Teipel, Stefan J.i; Hampel, Haraldi; Rapoport, Stanley I.f; Moeller, James R.g

doi: 10.1097/01.wnr.0000220135.16844.b6

Healthy aging has been associated with brain volume reductions preferentially affecting the frontal cortex, but also involving other regions. We used a network model of regional covariance, the Scaled Subprofile Model, with magnetic resonance imaging voxel-based morphometry to identify the regional distribution of gray matter associated with aging in 26 healthy adults, 22–77 years old. Scaled Subprofile Model analysis identified a pattern that was highly correlated with age (R2=0.66, P≤0.0001). Older age was associated with less gray matter in the bilateral frontal, temporal,thalamic, and right cerebellar regions. Gender differences suggested more advanced brain aging in the men. In this healthy adult sample, aging was associated with a regional pattern of gray matter atrophy most prominently involving the frontal and temporal cortices. Scaled Subprofile Model network analysis may aid in the detection and tracking of brain aging and in the evaluation of putative antiaging therapies.

aNeuroimage Analysis Laboratory, Department of Psychology, Arizona State University, Tempe

bBanner Alzheimer's Institute and Banner Samaritan PET Center, Banner Good Samaritan Medical Center, Phoenix

cDepartment of Psychiatry, University of Arizona Health Sciences Center, Tucson

dDepartment of Neurology, Mayo Clinic – Scottsdale, Scottsdale

eArizona Alzheimer's Disease Consortium, Arizona

fBrain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland

gDepartment of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA

hDepartment of Clinical Biochemistry and Molecular Biology, University of Pisa Medical School, Pisa, Italy

iDementia and Neuroimaging Research Section, Alzheimer's Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig Maximilian University, Munich, Germany

Correspondence and request for reprints to Dr Gene E. Alexander, PhD, Department of Psychology, Arizona State University, Tempe, AZ, 85287-1104, USA

Tel: +1 480 727 7790; fax: +1 480 965 8544; e-mail:

Sponsorship: This work was supported by the NIA Arizona Alzheimer's Disease Center (P30AG19610), the state-supported Arizona Alzheimer's Research Center, the NIMH (R01 MH57899) and the Alzheimer's Association (IIRG 02-3784).

Received 27 February 2006; accepted 9 March 2006

An early version of this work was presented, in part, at the meeting of the International Neuropsychological Society, Baltimore, Maryland, February 6, 2004.

© 2006 Lippincott Williams & Wilkins, Inc.