title: Influences of a DRD2 polymorphism on updating of long-term memory representations and caudate BOLD activity: magnification in aging.
abstract: A number of genetic polymorphisms are related to individual differences in cognitive performance. Striatal dopamine (DA) functions, associated with cognitive performance, are linked to the TaqIA polymorphism of the DRD2/ANKK1 gene. In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. The resource-modulation hypothesis assumes that aging-related losses of neurochemical and structural brain resources modulate the extent to which genetic variations affect cognitive functioning. Here, we tested this hypothesis using functional MRI during long-term memory (LTM) updating in younger and older carriers and noncarriers of the A1-allele of the TaqIa polymorphism. We demonstrate that older A1-carriers have worse memory performance, specifically during LTM updating, compared to noncarriers. Moreover, A1-carriers exhibited less blood oxygen level-dependent (BOLD) activation in left caudate nucleus, a region critical to updating. This effect was only seen in older adults, suggesting magnification of genetic effects on functional brain activity in aging. Further, a positive relationship between caudate BOLD activation and updating performance among non-A1 carriers indicated that caudate activation was behaviorally relevant. These results demonstrate a link between the DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM updating, and provide novel evidence that this effect is magnified in aging.
authors.affiliation: Aging Research Center (ARC), Karolinska Institute and Stockholm University, Gävlegatan 16, Stockholm, Sweden; Department of Psychology, Stockholm University, Stockholm, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Persson
authors.forename: Anna
authors.initials: A
authors.lastname: Rieckmann
authors.forename: Grégoria
authors.initials: G
authors.lastname: Kalpouzos
authors.forename: Håkan
authors.initials: H
authors.lastname: Fischer
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology / Q000502:physiology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000473:pathology / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000235:genetics / Q000502:physiology; D005260:Female; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D010100:Oxygen
keywords: DRD2; aging; dopamine; functional magnetic resonance imaging (fMRI); memory; striatum; updating