Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease
Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease
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DOI：
10.1007/8904_2014_315
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Saunders-Pullman, R.
中科院分区：
文献类型：
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作者：
Barrett, M. J.;Shanker, V. L.;Saunders-Pullman, R.
葡糖苷酶β-酸（GBA）突变与帕金森病（PD）和路易体痴呆的认知障碍相关。对于这两种疾病，痴呆和幻觉通常用胆碱酯酶抑制剂和抗精神病药治疗。然而，在某些溶酶体贮积症中，某些抗精神病药物的耐受性较差。本研究探讨胆碱酯酶抑制剂和抗精神病药在单等位基因GBA相关PD中的应用，以探索潜在的药物遗传学关系。将至少接受过两次门诊访视的单等位基因GBA突变PD携带者（GBA-PD）（n = 34）的发病年龄和性别与GBA和富含亮氨酸重复激酶2（LRRK 2）突变阴性的特发性PD受试者（IPD）（n = 60）匹配。获得了关于胆碱酯酶抑制剂和抗精神病药物使用以及认知受损（MRS精神障碍>1）和幻觉（MRS思维障碍>1）的信息。GBAPD更常报告幻觉（HR = 5.0; p - 0.01），他们更可能有认知障碍，但这不具有统计学显著性（HR 2.2，p - 0.07）。抗精神病药物的使用在GBA-PD和IPD之间没有显著差异（HR - 1.9; p - 0.28），但GBA-PD更可能持续使用胆碱酯酶抑制剂（HR = 3.1; p = 0.008），即使在调整认知和幻觉后。与认知能力较差的报告一致，与IPD相比，GBA-PD患者更有可能使用胆碱酯酶抑制剂。虽然IPD和GBA-PD之间的抗精神病药物使用没有差异，但GBA-PD患者持续使用奎替鲁表明其耐受性良好，不太可能发生显著的相互作用。需要在更大样本中进行更广泛的认知评估的进一步前瞻性研究，以更好地了解GBA-PD中的药物遗传学关系。
Mutations in glucosidase, beta, acid (GBA) are associated with cognitive impairment in Parkinson disease (PD) as well as dementia with Lewy bodies. For both of these diseases, dementia and hallucinations are typically treated with cholinesterase inhibitors and antipsychotics. However, in some lysosomal storage disorders certain antipsychotic medications are poorly tolerated. This study examined cholinesterase inhibitor and antipsychotic use in monoallelic GBA-related PD to explore potential pharmacogenetic relationships. Monoallelic GBA mutation carriers with PD (GBA-PD) with at least two clinic visits (n = 34) were matched for age-of-onset and gender to GBA and leucine-rich repeat kinase 2 (LRRK2) mutation negative idiopathic PD subjects (IPD) (n = 60). Information regarding cholinesterase inhibitor and antipsychotic use as well as impaired cognition (UPDRS Mentation >1) and hallucinations (UPDRS Thought Disorder >1) were obtained. GBAPD more frequently reported hallucinations (HR = 5.0; p - 0.01) and they were more likely to have cognitive impairment but this was not statistically significant (HR 2.2, p - 0.07). Antipsychotic use was not significantly different between GBA-PD and IPD (HR - 1.9; p - 0.28), but GBA-PD were more likely to have sustained cholinesterase inhibitor use (HR = 3.1; p = 0.008), even after adjustment for cognition and hallucinations. Consistent with reports of worse cognition, GBA-PD patients are more likely to use cholinesterase inhibitors compared to IPD. While there was no difference in antipsychotic use between IPD and GBA-PD, persistent use of quetiapine in GBA-PD suggests that it is tolerated and that a significant interaction is unlikely. Further prospective study in larger samples with more extensive cognitive assessment is warranted to better understand pharmacogenetic relationships in GBA-PD.