Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
Jarkko Johansson, Kristin Nordin, Robin Pedersen, Nina Karalija, Goran Papenberg, Micael Andersson, Saana M. Korkki, Katrine Riklund, Marc Guitart‐Masip, Anna Rieckmann, Lars Bäckman, Lars Nyberg, Alireza Salami
Abstract
Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.