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C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
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Number of Authors: 112019 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed) Published
Abstract [en]

The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.

Place, publisher, year, edition, pages
2019. Vol. 31, no 2, p. 314-325
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Psychology Neurosciences
Identifiers
URN: urn:nbn:se:su:diva-165644DOI: 10.1162/jocn_a_01354ISI: 000454429400011PubMedID: 30407135OAI: oai:DiVA.org:su-165644DiVA, id: diva2:1286962
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved

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