Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals

Objective: Although it is documented that brain dopamine activity declines with age, the functional significance of this is not known. This study assessed the relation between measures of brain dopamine activity and indexes of motor and cognitive function in healthy individuals. Method: Thirty healthy volunteers aged 24-86 years were studied with positron emission tomography and [¹¹C] raclopride to assess dopamine D₂ receptors. All subjects underwent a neuropsychological test battery that included tasks found to be sensitive to dopamine alterations in patients with neurodegenerative disease and control tasks. Results: Transfer of [¹¹C]- raclopride from plasma to brain in the striatum and cerebellum was not affected by age. In contrast, D₂ receptor availability in the caudate and putamen declined with age. Correlations between D₂ receptors and neuropsychological test performance were strongest for the motor task (Finger Tapping Test) and were also significant for most tasks involving frontal brain regions, including measures of abstraction and mental flexibility (Wisconsin Card Sorting Test) and attention and response inhibition (Stroop Color-Word Test, interference score). These relationships remained significant after control for age effects. Conclusions: Age-related decreases in brain dopamine activity are associated with a decline in motor function and may also contribute to impaired performance on tasks that involve frontal brain regions. Interventions that enhance dopamine activity may improve performance and quality of life for the elderly. The fact that correlations remained significant after age effects were partialed out suggests that dopamine activity may influence motor and cognitive performance irrespective of age.