Cognitive decline in prodromal Huntington Disease: implications for clinical trials.
Cognitive decline in prodromal Huntington Disease: implications for clinical trials.
复制标题
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
复制
发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
PREDICT HD investigators and Coordinators of the Huntington Study Group
中科院分区：
文献类型：
--
作者：
Paulsen JS;Smith MM;Long JD;PREDICT HD investigators and Coordinators of the Huntington Study Group
对于先兆亨廷顿病(HD)的预防性临床试验的可行性存在争议。一个主要的限制是缺乏对尚未被诊断为HD的基因突变患者的结果衡量标准。许多关于先兆HD患者认知功能下降的纵向研究没有根据疾病进展对样本进行分层，从而掩盖了有症状和无症状个体之间的差异。来自Forecast-HD的前驱受试者根据疾病进展被分成三组之一：那些在接下来的五年内有高、中或低概率运动表现的人。对总共N=1299名参与者的多达5950个数据点的数据进行了29个纵向认知变量的线性混合效应回归，控制了年龄、教育程度、抑郁和性别。随着时间的推移，三个先兆HD组的表现以潜伏的和显著的认知能力下降为特征。来自19个不同认知任务的21个变量显示了疾病进展梯度的证据，这意味着恶化速度作为进展水平的函数而不同，恶化速度越快，疾病进展越快。高水平组有19项指标出现明显的纵向变化，中等水平组有9项指标出现显著变化，低水平组有4项指标出现显著下降。结果表明，临床试验可以在先兆HD中使用指定的结果测量和方法进行。这一发现可能有助于对HD和其他神经退行性疾病进行干预。
Controversy exists regarding the feasibility of preventive clinical trials in prodromal Huntington disease (HD). A primary limitation is a lack of outcome measures for persons with the gene mutation who have not yet been diagnosed with HD. Many longitudinal studies of cognitive decline in prodromal HD have not stratified samples based on disease progression, thereby obscuring differences between symptomatic and nonsymptomatic individuals. Prodromal participants from PREDICT-HD were stratified by disease progression into one of three groups: those having a High, Medium, or Low probability of motor manifestation within the next five years. Data from a total of N = 1299 participants with up to 5950 data points were subjected to linear mixed effects regression on 29 longitudinal cognitive variables, controlling for age, education, depression, and gender. Performance of the three prodromal HD groups was characterized by insidious and significant cognitive decline over time. Twenty-one variables from 19 distinct cognitive tasks revealed evidence of a disease progression gradient, meaning that the rate of deterioration varied as a function of progression level, with faster deterioration associated with greater disease progression. Nineteen measures showed significant longitudinal change in the High group, nine showed significant change in the Medium group and four showed significant cognitive decline in the Low group. Results indicate that clinical trials may be conducted in prodromal HD using the outcome measures and methods specified. The findings may help inform interventions in HD as well as other neurodegenerative disorders.
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影响因子：
14.5
作者：
Lawrence, AD;Sahakian, BJ;Robbins, TW
通讯作者：
Robbins, TW
DOI：
10.1080/13803395.2011.574606
发表时间：
2011-01-01
影响因子：
2.2
作者：
Maroof, David Aaron;Gross, Alden L.;Brandt, Jason
通讯作者：
Brandt, Jason
影响因子：
5.7
作者：
Elsinger, C. L.;Harrington, D. L.;Rao, S. M.
通讯作者：
Rao, S. M.
影响因子：
5.8
作者：
Bostan, Andreea C.;Strick, Peter L.
通讯作者：
Strick, Peter L.
影响因子：
11
作者：
Campodonico, JR;Codori, AM;Brandt, J
通讯作者：
Brandt, J