TY - JOUR
T1 - A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging
AU - Karalija, Nina
AU - Köhncke, Ylva
AU - Düzel, Sandra
AU - Bertram, Lars
AU - Papenberg, Goran
AU - Demuth, Ilja
AU - Lill, Christina M.
AU - Johansson, Jarkko
AU - Riklund, Katrine
AU - Lövdén, Martin
AU - Bäckman, Lars
AU - Nyberg, Lars
AU - Lindenberger, Ulman
AU - Brandmaier, Andreas M.
N1 - Funding Information:
The COBRA study was funded by the Swedish Research Council, Umeå University, the Swedish Brain Foundation, Umeå University–Karolinska Institute Strategic Neuroscience Program, the Knut and Alice Wallenberg Foundation, the Torsten and Ragnar Söderberg Foundation, an Alexander von Humboldt Research award, a donation from the Jochnick Foundation, Swedish Brain Power, Västerbotten County Council, Innovation Fund of the Max Planck Society, and the and Gottfried Wilhelm Leibniz Research Award 2010 of the German Research Foundation (DFG). The Freesurfer analyses were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at HPC2N in Umeå, partially funded by the Swedish Research Council through grant agreement no. 2018-05973.
Funding Information:
This work reports data from the BASE-II project, which was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under grant numbers #01UW0808; #16SV5536K, #16SV5537, #16SV5538, #16SV5837; #01GL1716A; and #01GL1716B). Another sources of funding are the Max Planck Institute for Human Development, Berlin, Germany, and the European Commission as part of the Lifebrain Consortium (grant number 732592) within the Horizon 2020 program. Additional contributions (e.g. equipment, logistics, and personnel) are made from each of the other participating sites. Further details about the study can be obtained at www.base2.mpg.de . C.M. Lill was supported by the German Research Foundation (DFG, GZ LI 2654/2-1).
Publisher Copyright:
© 2021
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
AB - Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
UR - http://www.scopus.com/inward/record.url?scp=85118554159&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2021.118707
DO - 10.1016/j.neuroimage.2021.118707
M3 - Journal articles
C2 - 34742942
AN - SCOPUS:85118554159
SN - 1053-8119
VL - 245
JO - NeuroImage
JF - NeuroImage
M1 - 118707
ER -
