Dopamine D(1) receptors and age differences in brain activation during working memory.
In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.
Bäckman
Lars
L
Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden. lars.backman.1@ki.se
Karlsson
Sari
S
Fischer
Håkan
H
Karlsson
Per
P
Brehmer
Yvonne
Y
Rieckmann
Anna
A
MacDonald
Stuart W S
SW
Farde
Lars
L
Nyberg
Lars
L
D000328:Adult; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D001552:Benzazepines / Q000493:pharmacokinetics; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D055815:Young Adult
D001552:Benzazepines; D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D010100:Oxygen