Age-dependent decline of dopamine D1 receptors in human brain: a PET study.
Radioligand binding studies in animals have demonstrated age-related loss of dopamine receptors in the caudate and putamen. In humans, while age-related declines in dopamine D2 receptors have been consistently reported, the effects of ageing on D1 receptors have been controversial. We used positron emission tomography (PET) with [11C]SCH 23390 to investigate dopamine D1 receptor binding in 21 normal volunteers aged 22-74 years. We also assessed their motor function with a Modified Columbia Score (MCS) and the Purdue Pegboard Test (PPBT). D1 binding potentials were derived using a graphical analysis with a cerebellar tissue input function. Standard linear regression techniques were used to determine the age-related rate of decline of D1 binding. We found an age-dependent decrease of D1 receptor binding in the caudate (6.9% per decade) and putamen (7.4% per decade). There was also a significant inverse correlation between [11C]SCH 23390 binding in the occipital cortex and age (8.6% decline per decade). PPBT score also decreased with age (P = 0.007). There was a direct correlation between PPBT score and D1 binding potential. We conclude that dopamine D1 receptor density declines with age and that the effects of physiological ageing may play a role in the expression of extrapyramidal disorders in the elderly.
Neurodegenerative Disorders Centre and UBC-TRIUMF PET Group, Vancouver Hospital, UBC site, British Columbia, Canada.
Y
Y
Wang
G L
GL
Chan
J E
JE
Holden
T
T
Dobko
E
E
Mak
M
M
Schulzer
J M
JM
Huser
B J
BJ
Snow
T J
TJ
Ruth
D B
DB
Calne
A J
AJ
Stoessl
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001552:Benzazepines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002421:Caudate Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009778:Occipital Lobe / Q000378:metabolism; D011597:Psychomotor Performance; D011699:Putamen / Q000378:metabolism; D011859:Radiography; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000378:metabolism*; D012044:Regression Analysis; D014055:Tomography, Emission-Computed / Q000379:methods
D001552:Benzazepines; D002250:Carbon Radioisotopes; D017447:Receptors, Dopamine D1