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Cerebral Cortex Advance Access published online on January 29, 2008
Cerebral Cortex, doi:10.1093/cercor/bhm250
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Low Striatal Glutamate Levels Underlie Cognitive Decline in the Elderly: Evidence from In Vivo Molecular Spectroscopy

Natalie M. Zahr1,2, Dirk Mayer2,3, Adolf Pfefferbaum1,2 and Edith V. Sullivan1

1 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305-5723, USA, 2 Neuroscience Program, SRI International, Menlo Park, CA 94025, USA, 3 Radiology Department, Lucas MRS/I Center, Stanford University, 1201 Welch Road, P-273, Stanford, CA 94305-5488, USA

Address correspondence to email: edie{at}stanford.edu.

Glutamate (Glu), the principal excitatory neurotransmitter of prefrontal cortical efferents, potentially mediates higher order cognitive processes, and its altered availability may underlie mechanisms of age-related decline in frontally based functions. Although animal studies support a role for Glu in age-related cognitive deterioration, human studies, which require magnetic resonance spectroscopy for in vivo measurement of this neurotransmitter, have been impeded because of the similarity of Glu's spectroscopic signature to those of neighboring spectral brain metabolites. Here, we used a spectroscopic protocol, optimized for Glu detection, to examine the effect of age in 3 brain regions targeted by cortical efferents—the striatum, cerebellum, and pons—and to test whether performance on frontally based cognitive tests would be predicted by regional Glu levels. Healthy elderly men and women had lower Glu in the striatum but not pons or cerebellum than young adults. In the combined age groups, levels of striatal Glu (but no other proton metabolite also measured) correlated selectively with performance on cognitive tests showing age-related decline. The selective relations between performance and striatal Glu provide initial and novel, human in vivo support for age-related modification of Glu levels as contributing to cognitive decline in normal aging.

Key Words: aging • cognition • frontostriatal circuitry • glutamate • human • imaging


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