10-year longitudinal dopamine D2-receptor losses are associated with cognitive decline in healthy aging

Abstract

Aging-related dopamine decline has been suggested as a key factor behind individual differences in cognitive decline at older ages. Thus far, the hypothesized age-dopamine-cognition triad has been extrapolated from cross-sectional studies, which cannot uncover change associations. Using data from the longitudinal Cognition, Brain, and Aging (COBRA) study, we examined whether dopamine D2-receptor availability changes are correlated with cognitive changes across individuals in old age. At the first wave, 181 healthy adults aged 64 to 68 years underwent positron emission tomography with 11C-raclopride, magnetic resonance imaging, multiple cognitive tests assessing episodic memory, working memory, and perceptual speed, and mapping of health-related factors. The returnees (n = 129 after 5 years; n = 93 after 10 years) were representative of the parent sample regarding gender composition, educational attainment, cognitive performance, and dopamine D2-receptor status at baseline. Bayesian structural equation modeling revealed mean decline and individual differences in decline for striatal dopamine D2-receptor availability (approximately-5% per decade) and for all three cognitive abilities. Changes in dopamine D2-receptor and a factor of general cognition were positively correlated (r = 0.31, P(r > 0.00) > 0.95). Taken together, these longitudinal findings support that striatal dopamine decline is associated with cognitive aging, possibly reflecting dopamine influences via striato-Thalamo-cortical loops on general cognitive functions.