Investigation of the role of the dopamine transporter in susceptibility to behavioural and psychological symptoms of patients with probable Alzheimer's disease

Dement Geriatr Cogn Disord. 2008;26(3):257-60. doi: 10.1159/000160958. Epub 2008 Oct 8.

Abstract

Background/aims: Alzheimer's disease patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD); a genetic component to the development of BPSD has been demonstrated. Genetic risk factors for other psychiatric disorders have been implicated in BPSD; however, this is the first known investigation of the dopamine transporter (DAT1) gene in BPSD.

Methods: Our large cohort of 395 patients with probable Alzheimer's disease was dichotomised into whether they had ever suffered from a given symptom over the study period or not, based on longitudinal data using the BPSD (Neuropsychiatric Inventory). These measures were related to the DAT1 3'-untranslated region (UTR) variable number tandem repeat (VNTR) polymorphism.

Results: Potential associations were revealed between the 9-repeat allele and presence of irritability and between the 10-repeat allele and aberrant motor behaviour (AMB); however, these do not remain significant after correction for multiple testing. No associations were observed with delusions, hallucinations, depression, agitation/aggression or elation.

Conclusion: Our data suggest that the DAT1 3'-UTR VNTR could play a role in susceptibility to irritability and AMB. The findings presented here require replication in large well-characterised cohorts.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aged
  • Aged, 80 and over
  • Aggression / physiology
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology*
  • Cohort Studies
  • Depression / genetics
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Humans
  • Irritable Mood / physiology
  • Longitudinal Studies
  • Male
  • Mental Disorders / epidemiology
  • Mental Disorders / genetics*
  • Mental Disorders / psychology*
  • Phenotype
  • Risk Factors
  • Tandem Repeat Sequences

Substances

  • 3' Untranslated Regions
  • Dopamine Plasma Membrane Transport Proteins