journal of Neurology, Neurosurgery & Psychiatry:有症状和临床症状出现前遗传性颞颞叶变性的早期症状

2020-08-11 MedSci原创 MedSci原创

额颞叶痴呆(FTD)的临床异质性使用于临床试验的生物标志物的鉴定变得复杂,这些生物标志物在预诊断阶段可能很敏感。目前尚不清楚临床前时期的认知或行为变化是否可预测遗传状态或转换为临床FTD。第一个目标是

额颞叶痴呆(FTD)的临床异质性使用于临床试验的生物标志物的鉴定变得复杂,这些生物标志物在预诊断阶段可能很敏感。目前尚不清楚临床前时期的认知或行为变化是否可预测遗传状态或转换为临床FTD。第一个目标是评估遗传性FTD患者最常见的初始症状。第二个目的是评估临床前突变携带者相对于家族突变非携带者是否表现出独特的FTD相关症状。

方法:本研究使用了2012年至2018年间的遗传额颞叶研究数据。参与者包括9号染色体(C9orf72)的致病突变的症状携带者(n = 185),前颗粒蛋白(GRN)或微管相关蛋白tau(MAPT)及其一级生物学家族成员(n = 588)。使用线人和临床医师评定的量表记录症状数据。

                                                                                            不同病因症出现的症状比例

 

结果:在有症状患者中,最常见的初始症状是冷漠(23%),抑制力(18%),记忆力减退(12%),流利度降低(8%)和关节运动受损(5%)。主要的最初症状通常在家庭成员之间不一致。相对于生物学相关的非携带者,临床前的MAPT携带者认可了较差的情绪和睡眠症状,而C9orf72携带者认可了略微更大的异常行为。与非携带者相比,临床前GRN携带者认可的情绪症状更少,并且日常技能也较差。

结论:临床前突变携带者表现出神经精神症状,而非携带者则被认为是未来的临床试验结果。考虑到症状的异质性,可以通过综合每个基因组最常见的初始症状的综合指标来最好地捕获对症状性FTD的临床过渡检测。

参考文献:Tavares TPMitchell DGVColeman KK, et al Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration

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    2020-09-25 chg121
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    2021-04-11 yinhl1978
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    2020-08-13 lsndxfj
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    2020-08-13 huangdf

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