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
Affiliations
Nina Karalija
Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Umeå center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden; Corresponding author at: Diagnostic Radiology, Department of Radiation Sciences, Umeå University, SE 901 87 Umeå, Sweden
Ylva Köhncke
Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
Sandra Düzel
Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
Lars Bertram
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway
Goran Papenberg
Aging Research Center, Karolinska Institutet & Stockholm University, Solna, Sweden
Ilja Demuth
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, Berlin, Germany; Charité – Universitätsmedizin Berlin, BCRT - Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Christina M. Lill
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK
Jarkko Johansson
Umeå center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden
Katrine Riklund
Umeå center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden
Martin Lövdén
Department of psychology, University of Gothenburg, Gothenburg, Sweden
Lars Bäckman
Aging Research Center, Karolinska Institutet & Stockholm University, Solna, Sweden
Lars Nyberg
Umeå center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
Ulman Lindenberger
Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany, and London, UK
Andreas M. Brandmaier
Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany, and London, UK
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.
