Dopaminergic gene polymorphisms affect long-term forgetting in old age: further support for the magnification hypothesis

J Cogn Neurosci. 2013 Apr;25(4):571-9. doi: 10.1162/jocn_a_00359. Epub 2013 Jan 30.

Abstract

Emerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger (n = 433, 20-31 years) and older (n = 690, 59-71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Analysis of Variance
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Memory Disorders / genetics*
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Recognition, Psychology / physiology
  • Young Adult

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • SLC6A3 protein, human