Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion.

Introduction: Genetic variants in DAT1, the gene encoding the dopamine transporter (DAT) protein, have been implicated in many brain disorders. In a recent case-control study of Alzheimer's disease (AD), a regulatory polymorphism in DAT1 showed a significant association with the clinical stages of dementia.

Methods: We tested whether this variant was associated with increased AD risk, and with measures of cognitive decline and longitudinal ventricular expansion, in a large sample of elderly participants with genetic, neurocognitive, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative.

Results: The minor allele-previously linked with increased DAT expression in vitro-was more common in AD patients than in both individuals with mild cognitive impairment and healthy elderly controls. The same allele was also associated with poorer cognitive performance and faster ventricular expansion, independently of diagnosis.

Discussion: These results may be due to reduced dopaminergic transmission in carriers of the DAT1 mutation.