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The Journal of Neuroscience, December 24, 2008, 28(52):14320-14328; doi:10.1523/JNEUROSCI.3729-08.2008

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Neurobiology of Disease
Relationship of Striatal Dopamine Synthesis Capacity to Age and Cognition

Meredith N. Braskie,^1,2 Claire E. Wilcox,^1,3 Susan M. Landau,^1,2 James P. O'Neil,² Suzanne L. Baker,² Cindee M. Madison,¹ Jennifer T. Kluth,^1,2 and William J. Jagust^1,2

¹Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California 94720-3192, ²Department of Functional Imaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and ³Department of Psychiatry, University of California, San Francisco, San Francisco, California 94143

Correspondence should be addressed to Dr. Meredith N. Braskie, Helen Wills Neuroscience Institute, 132 Barker Hall, MC#3190, Berkeley, CA 94720-3192. Email: mbraskie{at}berkeley.edu

Past research has demonstrated that performance on frontal lobe-dependent tasks is associated with dopamine system integrity and that various dopamine system deficits occur with aging. The positron emission tomography (PET) radiotracer 6-[¹⁸F]fluoro-L-m-tyrosine (FMT) is a substrate of the dopamine-synthesizing enzyme, aromatic amino acid decarboxylase (AADC). Studies using 6-[¹⁸F]fluorodopa (FDOPA) (another AADC substrate) to measure how striatal PET signal and age relate have had inconsistent outcomes. The varying results occur in part from tracer processing that renders FDOPA signal subject to aspects of postrelease metabolism, which may themselves change with aging. In contrast, FMT remains a purer measure of AADC function. We used partial volume-corrected FMT PET scans to measure age-related striatal dopamine synthesis capacity in 21 older (mean, 66.9) and 16 younger (mean, 22.8) healthy adults. We also investigated how striatal FMT signal related to a cognitive measure of frontal lobe function. Older adults showed significantly greater striatal FMT signal than younger adults. Within the older group, FMT signal in dorsal caudate (DCA) and dorsal putamen was greater with age, suggesting compensation for deficits elsewhere in the dopamine system. In younger adults, FMT signal in DCA was lower with age, likely related to ongoing developmental processes. Younger adults who performed worse on tests of frontal lobe function showed greater FMT signal in right DCA, independent of age effects. Our data suggest that higher striatal FMT signal represents nonoptimal dopamine processing. They further support a relationship between striatal dopamine processing and frontal lobe cognitive function.

Key words: FMT; PET; normal aging; striatum; cognition; aromatic amino acid decarboxylase; DOPA decarboxylase; caudate; putamen; basal ganglia; prefrontal; upregulation

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Received Aug. 6, 2008; revised Sept. 25, 2008; accepted Nov. 13, 2008.

Correspondence should be addressed to Dr. Meredith N. Braskie, Helen Wills Neuroscience Institute, 132 Barker Hall, MC#3190, Berkeley, CA 94720-3192. Email: mbraskie{at}berkeley.edu

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