Influences of a DRD2 polymorphism on updating of long-term memory representations and caudate BOLD activity: magnification in aging

Hum Brain Mapp. 2015 Apr;36(4):1325-34. doi: 10.1002/hbm.22704. Epub 2014 Dec 9.

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.

Keywords: DRD2; aging; dopamine; functional magnetic resonance imaging (fMRI); memory; striatum; updating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / genetics*
  • Aging / pathology
  • Aging / physiology*
  • Brain Mapping
  • Caudate Nucleus / pathology
  • Caudate Nucleus / physiology*
  • Cerebrovascular Circulation / genetics
  • Cerebrovascular Circulation / physiology
  • Female
  • Genotyping Techniques
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Long-Term / physiology*
  • Neuropsychological Tests
  • Organ Size
  • Oxygen / blood
  • Polymorphism, Single Nucleotide*
  • Protein-Serine-Threonine Kinases / genetics
  • Receptors, Dopamine D2 / genetics*
  • Young Adult

Substances

  • DRD2 protein, human
  • Receptors, Dopamine D2
  • ANKK1 protein, human
  • Protein-Serine-Threonine Kinases
  • Oxygen