J16 The Effect Of Dopamine Blockade On Cognition In Huntington’s Disease

Background Huntington’s disease (HD) is an autosomal dominant condition which leads to progressive neurodegeneration and presents with a combination of motor, cognitive, affective and metabolic problems. Diagnosis of manifest HD currently relies solely on the motor features but in recent years increasing evidence has shown that the cognitive abnormalities begin before the motor features. In the brain, the HD pathology is known to affect the dopaminergic system with an early decrease in dopamine receptor 2 expression in the striatum but also other regions including the hippocampus. Interestingly, one of the most commonly used treatments for many of the features of HD block these same dopamine receptors. Aims This study therefore aims to investigate the effect of an acute dose of a commonly used dopamine receptor blocker, sulpiride, on the cognition of HD gene carriers compared to healthy controls. Methods 15 early manifest HD patients and 15 healthy controls received one dose of 200 mg of sulpiride and placebo in identical capsules in a randomised fashion. 90 min following the administration of the drug or placebo, participants were tested on a number of cognitive tasks from the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as a novel hippocampal-dependent test and a risk taking task. This study has a within-subjects double-blind placebo-controlled cross-over design to minimise confounding drug effects and to allow for increased statistical power. Outcome Previous data from a pilot study in our clinic found that a similar study in a small group of manifest HD patients showed an improvement in their cognitive performance in two hippocampal tasks after taking the sulpiride. This study is therefore aiming to extend this work to investigate the effect of this drug on cognition in patient at an earlier stage of the disease process and compare it to matched controls. The study is ongoing at the moment, but hope to have preliminary results by the end of August, ready to be presented at the conference.