Pharmacogenetics of Non-Motor Symptoms in Parkinson\u27s Disease

Memory deficits are recognized in Parkinson’s disease (PD). The nature of these memory deficits is unclear because few studies have both isolated memory encoding and retrieval processes while testing patients on and off their dopamine replacement medication. Previous work suggests encoding depends upon regions innervated by the ventral tegmental area, which is relatively spared in PD, while retrieval depends upon dorsal striatum, which is dopamine deficient even early in PD. We investigated the impact of a dopamine transporter (DAT1), a dopamine reuptake protein, polymorphism (a 40-base-pair variable repeat affecting expression) on encoding and retrieval in healthy, elderly controls as well as in patients on and off medication. We only found encoding deficits in PD patients who carry a DAT1 polymorphism when on, relative to off, medication, suggesting interactive effects of medication and genotype. We found improvements in memory retrieval in patients who were on, relative to off, medication, but this effect may be independent of DAT1 genotype. This work demonstrates the need for further investigation of interactive effects of medication and genetic profile in PD