A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging

Nina Karalija*, Ylva Köhncke, Sandra Düzel, Lars Bertram, Goran Papenberg, Ilja Demuth, Christina M. Lill, Jarkko Johansson, Katrine Riklund, Martin Lövdén, Lars Bäckman, Lars Nyberg, Ulman Lindenberger, Andreas M. Brandmaier

*Corresponding author for this work
3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number118707
JournalNeuroImage
Volume245
ISSN1053-8119
DOIs
Publication statusPublished - 15.12.2021

Cite this