Abstract：
Cognitive impairment is a central feature of Huntington\'s disease (HD), but it is unclear to what extent more aggressive cognitive phenotypes exist in HD among individuals with the same genetic load and equivalence in other clinical and sociodemographic variables.
We included Enroll-HD study participants in early and early-mid stages of HD at baseline and with three consecutive yearly follow-ups for whom several clinical and sociodemographic as well as cognitive measures were recorded. We excluded participants with low and large CAG repeat length (CAG < 39 & > 55), with juvenile or late onset HD, and with dementia at baseline. We explored the existence of different groups according to the profile of cognitive progression using a two-step k-means cluster analysis model based on the combination of different cognitive outcomes.
We identified a slow cognitive progression group of 293 participants and an aggressive progression group (F-CogHD) of 235 for which there were no differences at the baseline visit in any of the measures explored, with the exception of a slightly higher motor score in the F-CogHD group. This group showed a more pronounced annual loss of functionality and a more marked motor and psychiatric deterioration.
The rate of progression of cognitive deterioration in HD is strongly variable even between patients sharing, among other variables, equivalent CAG repeat length, age, and disease duration. We can recognize at least two phenotypes that differ in terms of rate of progression. Our findings open new avenues to study additional mechanisms contributing to HD heterogeneity.
We included Enroll-HD study participants in early and early-mid stages of HD at baseline and with three consecutive yearly follow-ups for whom several clinical and sociodemographic as well as cognitive measures were recorded. We excluded participants with low and large CAG repeat length (CAG < 39 & > 55), with juvenile or late onset HD, and with dementia at baseline. We explored the existence of different groups according to the profile of cognitive progression using a two-step k-means cluster analysis model based on the combination of different cognitive outcomes.
We identified a slow cognitive progression group of 293 participants and an aggressive progression group (F-CogHD) of 235 for which there were no differences at the baseline visit in any of the measures explored, with the exception of a slightly higher motor score in the F-CogHD group. This group showed a more pronounced annual loss of functionality and a more marked motor and psychiatric deterioration.
The rate of progression of cognitive deterioration in HD is strongly variable even between patients sharing, among other variables, equivalent CAG repeat length, age, and disease duration. We can recognize at least two phenotypes that differ in terms of rate of progression. Our findings open new avenues to study additional mechanisms contributing to HD heterogeneity.
摘要：
目的：认知障碍是亨廷顿病（HD）的主要特征，但尚不清楚在具有相同遗传负荷和其他临床和社会人口统计学变量等效性的个体中，HD中存在多大程度上更具攻击性的认知表型。
方法：我们纳入了Enroll-HD研究参与者，这些参与者在基线时处于HD的早期和早期中期阶段，并且每年连续进行三次随访，记录了一些临床和社会人口统计学以及认知测量。我们排除了CAG重复长度较低和较大（CAG<39&>55）的参与者，患有青少年或迟发性HD，和基线时的痴呆症。我们根据认知进展的概况，使用基于不同认知结果组合的两步k-means聚类分析模型，探索不同群体的存在。
结果：我们确定了293名参与者的缓慢认知进展组和235名积极进展组（F-CogHD），在基线访视时，所探讨的任何指标均无差异。除了F-CogHD组的运动评分略高。该组显示出更明显的年度功能丧失以及更明显的运动和精神恶化。
结论：即使在患者之间，HD的认知恶化的进展速度也存在很大差异，在其他变量中，等效CAG重复长度，年龄,和疾病持续时间。我们可以识别至少两种在进展速率方面不同的表型。我们的发现为研究导致HD异质性的其他机制开辟了新的途径。
方法：我们纳入了Enroll-HD研究参与者，这些参与者在基线时处于HD的早期和早期中期阶段，并且每年连续进行三次随访，记录了一些临床和社会人口统计学以及认知测量。我们排除了CAG重复长度较低和较大（CAG<39&>55）的参与者，患有青少年或迟发性HD，和基线时的痴呆症。我们根据认知进展的概况，使用基于不同认知结果组合的两步k-means聚类分析模型，探索不同群体的存在。
结果：我们确定了293名参与者的缓慢认知进展组和235名积极进展组（F-CogHD），在基线访视时，所探讨的任何指标均无差异。除了F-CogHD组的运动评分略高。该组显示出更明显的年度功能丧失以及更明显的运动和精神恶化。
结论：即使在患者之间，HD的认知恶化的进展速度也存在很大差异，在其他变量中，等效CAG重复长度，年龄,和疾病持续时间。我们可以识别至少两种在进展速率方面不同的表型。我们的发现为研究导致HD异质性的其他机制开辟了新的途径。
