Aging-related losses in dopamine D2/3 receptor availability are linked to working-memory decline across five years
Goran Papenberg, Nina Karalija, Alireza Salami, Jarkko Johansson, Anders Wåhlin, Micael Andersson, Jan Axelsson, Douglas D Garrett, Katrine Riklund, Ulman Lindenberger, Lars Nyberg, Lars BäckmanAbstract
Although age differences in the dopamine system have been suggested to contribute to age-related cognitive decline based on cross-sectional data, recent large-scale cross-sectional studies reported only weak evidence for a correlation among aging, dopamine receptor availability, and cognition. Regardless, longitudinal data remain essential to make robust statements about dopamine losses as a basis for cognitive aging. We present correlations between changes in D2/3 dopamine receptor availability and changes in working memory measured over 5 yr in healthy, older adults (n = 128, ages 64 to 68 yr at baseline). Greater decline in D2/3 dopamine receptor availability in working memory-relevant regions (caudate, middle frontal cortex, hippocampus) was related to greater decline in working memory performance in individuals who exhibited working memory reductions across time (n = 43; caudate: rs = 0.494; middle frontal cortex: rs = 0.506; hippocampus; rs = 0.423), but not in individuals who maintained performance (n = 41; caudate: rs = 0.052; middle frontal cortex: rs = 0.198; hippocampus; rs = 0.076). The dopamine–working memory link in decliners was not observed in the orbitofrontal cortex, which does not belong to the core working memory network. Our longitudinal analyses support the notion that aging-related changes in the dopamine system contribute to working memory decline in aging.