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 Bäckman

Aging Research Center, Karolinska Institutet and Stockholm University, Tomtebodavägen 18 A, SE-171 65 Solna, Sweden.Aging Research Center, Karolinska Institutet and Stockholm University, Tomtebodavägen 18 A, SE-171 65 Solna, Sweden. · pubmed

Paper

Abstract

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.

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Research summary

The paper investigates the relationship between dopamine D2/3 receptor availability and working memory decline in aging, contributing to the understanding of cognitive aging mechanisms. While it provides valuable longitudinal data, its findings are somewhat incremental and primarily focus on correlational aspects rather than addressing root causes of aging or proposing interventions for lifespan extension. Thus, it has solid research value but limited broader impact on the field of longevity.

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