Bi-phasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan

The dopamine (DA) system, particularly D1-like DA receptors (D1DR), declines across the adult life. The functional consequences of reduced D1DR has been hypothesized to vary across life periods, but the precise timing of these periods is unknown. To examine distinct phases in age-related D1DR reductions, we studied 180 healthy adults (90 females, 20-80 years), who underwent D1DR PET assessment using [11C]SCH23390. A bi-phasic pattern of age-related D1DR differences was revealed, with an inflection point at approximately 40 years of age. Notably, D1DR levels before and after the inflection showed opposing relations to neurocognitive functions, in concordance with distinct consequences of D1DR differences during development and in old age. Furthermore, D1DR reductions in later life were linked to age-related cerebrovascular consequences. These results support a distinction between D1DR reductions in early adulthood from those later in life, and suggest less dramatic and more malleable DA losses in aging than previously suggested.