Investigation of the Role of the Dopamine Transporter in Susceptibility to Behavioural and Psychological Symptoms of Patients with Probable Alzheimer's Disease

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.