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.