Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study
Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study
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DOI：
10.1212/wnl.0b013e318253d54b
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发表时间：
2012-05-01
期刊：
影响因子：
9.9
通讯作者：
Marder, K.
中科院分区：
文献类型：
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作者：
Alcalay, R. N.;Caccappolo, E.;Marder, K.
目的：评估葡萄糖脑苷脂酶（GBA）突变携带者与早发性帕金森病（PD）的认知表型。方法：我们对参与CORE-PD研究的参与者进行了神经心理电池和宾夕法尼亚大学帕金森病识别测试（UPSIT），这些参与者接受了PARKIN，LRRK 2和GBA突变的检测。参与者包括33名GBA突变携带者和60名任何基因突变的非携带者。对26例无其他突变的GBA杂合突变携带者和39例年龄和PD持续时间匹配的非携带者进行了初步分析。五个认知领域，心理速度，注意力，记忆力，视觉空间功能，和执行功能，从个人神经心理测试的转换z分数。临床诊断（正常、轻度认知障碍[MCI]、痴呆）根据神经心理学表现和功能障碍（通过临床痴呆评定（CDR）评分评估）盲分配基因型。GBA突变状态和神经心理性能，CDR和临床诊断之间的关联进行了assessed.Results：人口统计学，UPSIT，和统一帕金森氏病评定量表-III的性能没有GBA运营商和非运营商之间的差异。GBA突变携带者在简易精神状态检查（p = 0.035）、记忆（p = 0.017）和视觉空间（p = 0.028）领域的表现比非携带者差。最显著的差异是在非文字记忆表现（p < 0.001）。携带者CDR评分> 0.5（p < 0.001），临床诊断为MCI或痴呆（p = 0.004）。结论：GBA基因突变可能是PD患者认知功能损害的独立危险因素。神经病学（R）2012;78：1434-1440
Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD).Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed.Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004).Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD. Neurology (R) 2012;78:1434-1440