The role of the striatal dopamine transporter in cognitive aging.
We examined the relationship of age-related losses of striatal dopamine transporter (DAT) density to age-related deficits in episodic memory and executive functioning in a group of subjects (n = 12) ranging from 34 to 81 years of age. The radioligand [(11)C]beta-CIT-FE was used to determine DAT binding in caudate and putamen. Results showed clear age-related losses of striatal DAT binding from early to late adulthood, and a marked deterioration in episodic memory (word and figure recall, face recognition) and executive functioning (visual working memory, verbal fluency) with advancing age. Most importantly, the age-related cognitive deficits were mediated by reductions in DAT binding, whereas DAT binding added systematic cognitive variance after controlling for age. Further, interindividual differences in DAT binding were related to performance in a test of crystallized intelligence (the Information subtest from the Wechsler Adult Intelligence Scale-Revised) that showed no reliable age variation. These results suggest that DAT binding is a powerful mediator of age-related cognitive changes as well as of cognitive functioning in general. The findings were discussed relative to the view that the frontostriatal network is critically involved in multiple cognitive functions.
Erixon-Lindroth
Nina
N
Department of Psychiatry, Department of Clinical Neuroscience, Karolinska Hospital, Box 6401, S-113 82 Stockholm, Sweden.
Farde
Lars
L
Wahlin
Tarja-Brita Robins
TB
Sovago
Judit
J
Halldin
Christer
C
Bäckman
Lars
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001665:Binding Sites; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D003072:Cognition Disorders / Q000175:diagnosis / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008569:Memory Disorders / Q000175:diagnosis / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009483:Neuropsychological Tests; D009662:Nortropanes; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011877:Radionuclide Imaging / Q000295:instrumentation; D021641:Recognition, Psychology
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C097058:N-(2-fluoroethyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; C493214:SLC6A3 protein, human