Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain activity during working memory.
BACKGROUND
Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity.


METHODS
We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults.


RESULTS
An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response.


CONCLUSIONS
These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.
Fischer
Håkan
H
Aging Research Center, Karolinska Institute, Stockholm, Sweden. hakan.fischer@ki.se
Nyberg
Lars
L
Karlsson
Sari
S
Karlsson
Per
P
Brehmer
Yvonne
Y
Rieckmann
Anna
A
MacDonald
Stuart W S
SW
Farde
Lars
L
Bäckman
Lars
L
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000494:pharmacology*; 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 / Q000379:methods; D016037:Single-Blind Method; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D001552:Benzazepines; D018492:Dopamine Antagonists; C534628:SCH 23390; D010100:Oxygen