H54 Investigation of the effects of dopamine antagonist medication on cognition in huntington’s disease

Kate L Harris, S. Mason, R. Barker
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Abstract

Whilst the diagnosis of Huntington’s disease (HD) is reliant on the presence of motor disturbances, progressive cognitive impairments can precede overt motor features by up to 15 years (Paulsen, 2011) and often place the greatest burden on both HD patients and their families (Brandt and Butters, 1986). It has been hypothesised that there is an increase in DA transmission in early stages of HD as drugs that block DA receptors help alleviate the chorea (Cepeda, 2015). However, despite knowing that DA is critical for cognition in a healthy population, little is understood about the consequences of these early changes on cognition in HD. Importantly, it is not known this process if influenced by the DA antagonists used to treat motor features of HD. In this study we use the dataset from Enroll-HD, the world’s largest observational study for Huntington’s disease families, to assess the effects of dopamine antagonist medication on cognitive decline. Participants were grouped into those taking dopamine antagonist medication during the assessment period and a control group who were not taking DA medication but were matched for age, gender and disease stage using propensity score matching. Results showed that participants taking DA antagonists had a significantly greater annual decline in performance on the enrol cognitive task battery than those who were not on DA medication. Furthermore, a group of participants who came off dopamine antagonists during the assessment period did not differ from the control group in rate of cognitive decline during the period they were off the medication. Together these results suggest that dopamine antagonist medication may be detrimental to cognition, which has important implications for the clinical management of cognitive symptoms.
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H54多巴胺拮抗剂对亨廷顿病认知功能影响的研究
虽然亨廷顿舞蹈病(HD)的诊断依赖于运动障碍的存在,但进行性认知障碍可能比明显的运动特征早15年(Paulsen, 2011),并且通常给亨廷顿舞蹈病患者及其家人带来最大的负担(Brandt和Butters, 1986)。据推测,在HD的早期阶段,由于阻断DA受体的药物有助于缓解舞蹈病,DA的传播会增加(Cepeda, 2015)。然而,尽管知道DA对健康人群的认知至关重要,但对这些早期变化对HD患者认知的影响知之甚少。重要的是,尚不清楚这一过程是否受到用于治疗HD运动特征的DA拮抗剂的影响。在这项研究中,我们使用来自世界上最大的亨廷顿病家族观察性研究Enroll-HD的数据集来评估多巴胺拮抗剂药物对认知能力下降的影响。参与者被分为在评估期间服用多巴胺拮抗剂药物的组和不服用多巴胺拮抗剂药物的对照组,但使用倾向评分匹配对年龄、性别和疾病阶段进行匹配。结果显示,服用DA拮抗剂的参与者在认知任务电池上的年度表现下降幅度明显大于未服用DA药物的参与者。此外,在评估期间停用多巴胺拮抗剂的一组参与者在停药期间的认知衰退率与对照组没有差异。总之,这些结果表明多巴胺拮抗剂药物可能对认知有害,这对认知症状的临床管理具有重要意义。
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