Mild Cognitive Impairment as an Early Landmark in Huntington's Disease.
Mild Cognitive Impairment as an Early Landmark in Huntington's Disease.
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DOI：
10.3389/fneur.2021.678652
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发表时间：
2021
影响因子：
3.4
通讯作者：
Paulsen JS
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhou J;Gehl CR;Long JD;Johnson H;Magnotta VA;Sewell D;Shannon K;Paulsen JS
作为亨廷顿病（HD）的临床三联征之一，认知障碍在HD文献中尚未被广泛接受为疾病分期指标。这项工作旨在利用一项为期 12 年的观察性研究数据，彻底研究 HD 前驱个体的认知障碍，以确定 HD 基因突变携带者中的轻度认知障碍 (MCI) 是否是早期疾病的可靠指标。 2002 年 9 月至 2014 年 4 月期间，每年在全球 32 个地点之一对前驱 HD 基因突变携带者进行评估，评估其在六个认知领域的 MCI。使用线性混合效应模型来确定 MCI 认知评估中年龄、教育程度和重新测试调整的截止值，然后评估 MCI 的并发有效性和预测有效性。加速失效时间 (AFT) 模型用于确定 MCI（单域、双域和多域）和痴呆的发生时间，痴呆被定义为 MCI 加功能丧失。 768 名前驱 HD 参与者完成了所有六项认知任务，进行了 MRI 扫描，并接受了纵向评估。超过一半（即 54%）的参与者在进入研究时患有 MCI，其中一半患有单域 MCI。与认知能力完整的参与者相比，患有 MCI 的前驱 HD 具有更高的遗传负担、更严重的运动障碍、更大的脑萎缩以及更高的估计 HD 发病的可能性。对基线时没有 MCI 的人进行的前瞻性纵向研究表明，48% 的人在随后的就诊中患有 MCI，数据可视化表明单域 MCI、两域 MCI 和痴呆代表了 HD 基因突变携带者的适当认知障碍分期。研究结果表明，MCI 代表了 HD 的早期里程碑，并且可能是疾病修饰治疗的前驱临床试验的敏感富集变量或终点。
As one of the clinical triad in Huntington's disease (HD), cognitive impairment has not been widely accepted as a disease stage indicator in HD literature. This work aims to study cognitive impairment thoroughly for prodromal HD individuals with the data from a 12-year observational study to determine whether Mild Cognitive Impairment (MCI) in HD gene-mutation carriers is a defensible indicator of early disease. Prodromal HD gene-mutation carriers evaluated annually at one of 32 worldwide sites from September 2002 to April 2014 were evaluated for MCI in six cognitive domains. Linear mixed-effects models were used to determine age-, education-, and retest-adjusted cut-off values in cognitive assessment for MCI, and then the concurrent and predictive validity of MCI was assessed. Accelerated failure time (AFT) models were used to determine the timing of MCI (single-, two-, and multiple-domain), and dementia, which was defined as MCI plus functional loss. Seven hundred and sixty-eight prodromal HD participants had completed all six cognitive tasks, had MRI, and underwent longitudinal assessments. Over half (i.e., 54%) of the participants had MCI at study entry, and half of these had single-domain MCI. Compared to participants with intact cognitive performances, prodromal HD with MCI had higher genetic burden, worsened motor impairment, greater brain atrophy, and a higher likelihood of estimated HD onset. Prospective longitudinal study of those without MCI at baseline showed that 48% had MCI in subsequent visits and data visualization suggested that single-domain MCI, two-domain MCI, and dementia represent appropriate cognitive impairment staging for HD gene-mutation carriers. Findings suggest that MCI represents an early landmark of HD and may be a sensitive enrichment variable or endpoint for prodromal clinical trials of disease modifying therapeutics.
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前驱亨廷顿疾病的认知能力下降：对临床试验的影响。
DOI：
10.1136/jnnp-2013-305114
发表时间：
2013-11
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Paulsen JS;Smith MM;Long JD;PREDICT HD investigators and Coordinators of the Huntington Study Group
通讯作者：
PREDICT HD investigators and Coordinators of the Huntington Study Group
影响因子：
3.1
作者：
Harrington, Deborah L.;Liu, Dawei;Smith, Megan M.;Mills, James A.;Long, Jeffrey D.;Aylward, Elizabeth H.;Paulsen, Jane S.
通讯作者：
Paulsen, Jane S.
影响因子：
158.5
作者：
Petersen, RC;Thomas, RG;Thal, LJ
通讯作者：
Thal, LJ
影响因子：
8.6
作者：
Hogarth, P;Kayson, E;Zhao, HW
通讯作者：
Zhao, HW
影响因子：
3.5
作者：
Kim, Eun Young;Johnson, Hans J.
通讯作者：
Johnson, Hans J.