Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
Nina Karalija, Goran Papenberg, Jarkko Johansson, Anders Wåhlin, Alireza Salami, Micael Andersson, Jan Axelsson, Dmitry V. Kuznetsov, Katrine Riklund, Martin Lövdén, Ulman Lindenberger, Lars Bäckman, Lars Nyberg
Abstract
Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n=181, age: 64–68 years; 5-year follow-up: n=129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n=47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n=72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.