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C957T-mediated Vari...
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Karalija, Nina,1984-Umeå universitet,Diagnostisk radiologi
(author)
C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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MIT Press,2019
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Numbers
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LIBRIS-ID:oai:DiVA.org:su-165644
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-165644URI
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https://doi.org/10.1162/jocn_a_01354DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-155630URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:139902107URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Papenberg, GoranKarolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI)
(author)
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Wåhlin, AndersUmeå universitet,Radiofysik,Umeå centrum för funktionell hjärnavbildning (UFBI)(Swepub:umu)arswan02
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Johansson, JarkkoUmeå universitet(Swepub:umu)jajo0061
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Andersson, MicaelUmeå universitet(Swepub:umu)mian0001
(author)
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Axelsson, Jan,1966-Umeå universitet(Swepub:umu)jaax0004
(author)
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Riklund, KatrineUmeå universitet(Swepub:umu)kaah0001
(author)
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Lövdén, MartinKarolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI)
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Lindenberger, Ulman
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Bäckman, LarsKarolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI)
(author)
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Nyberg, Lars,1966-Umeå universitet(Swepub:umu)lany0001
(author)
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Umeå universitetDiagnostisk radiologi
(creator_code:org_t)
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In:Journal of cognitive neuroscience: MIT Press31:2, s. 314-3250898-929X1530-8898
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Karalija, Nina, ...
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Papenberg, Goran
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Wåhlin, Anders
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Johansson, Jarkk ...
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Andersson, Micae ...
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Axelsson, Jan, 1 ...
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Riklund, Katrine
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Lövdén, Martin
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Nyberg, Lars, 19 ...
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- About the subject
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- SOCIAL SCIENCES
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SOCIAL SCIENCES
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and Psychology
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and Basic Medicine
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and Neurosciences
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Stockholm University
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Umeå University
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Karolinska Institutet