Background

Huntington’s disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood. The aim of this study was to investigate the specific structural brain correlates of major cognitive deficits in HD and to explore its association with neuropsychological indicators.

Participants

Thirty-five symptomatic early-to-mild HD patients and 15 healthy controls (HC) with available T1-MRI imaging were included in this study.

Methods

In this cross-sectional study, HD patients were classified as patients with (HD-Dem) and without (HD-ND) major cognitive impairment in the range of dementia. This classification was based on previously validated PD-CRS cutoff scores for HD. Differences in brain atrophy across groups were studied by means of grey-matter volume voxel-based morphometry (GMV-VBM) and cortical thickness (Cth). Voxelwise and vertexwise general linear models were used to assess the group comparisons, controlling for the effects of age, sex, education, CAG repeat length and severity of motor symptoms. Clusters surviving p < 0.05 and family-wise error (FWE) correction were considered statistically significant. In order to characterize the impact on cognitive performance of the observed brain differences across groups, GMV and Cth values in the set of significant regions were computed and correlated with specific neuropsychological tests.

Results

All groups had similar sociodemographic profiles, and the HD groups did not significantly differ in terms of CAG repeat length. Compared to HC, both HD groups exhibited significant atrophy in multiple subcortical and parietal brain regions. However, compared to HC and HD-ND groups, HD-Dem patients showed a more prominent pattern of reduced GMV and cortical thinning. Importantly, this thinning was restricted to regions of the parietal-temporal and occipital cortices. Furthermore, these brain alterations were further associated with poorer cognitive performance in tasks assessing frontal-executive and attention domains as well as memory, language and constructional abilities.

Conclusions

Major cognitive impairment in the range of dementia in HD is associated with brain and cognitive alterations exceeding the prototypical frontal-executive deficits commonly recognized in HD. The observed posterior-cortical damage identified by MRI and its association with memory, language, and visuoconstructive dysfunction suggest a strong involvement of extra-striatal atrophy in the onset of severe cognitive dysfunction in HD patients. Critically, major cognitive impairment in this sample was not associated with CAG repeat length, age or education. This finding could support a possible involvement of additional neuropathological mechanisms aggravating cognitive deterioration in HD.

中文翻译：

---

亨廷顿舞蹈病痴呆的结构性脑相关性

背景

亨廷顿舞蹈病（HD）是一种致命的遗传性神经退行性疾病，目前尚无有效的治疗方法。进行性基底神经节和全脑萎缩以及并发的认知能力下降是HD的典型特征。然而，人们对HD严重程度不同的认知障碍背后的脑萎缩的具体模式了解甚少。这项研究的目的是调查HD中主要认知缺陷的特定结构性脑相关性，并探讨其与神经心理学指标的关系。

参加者

该研究包括35例有症状的早期至轻度HD患者和15例具有可用T1-MRI成像的健康对照（HC）。

方法

在这项横断面研究中，HD患者被分为痴呆症范围内的（HD-Dem）和无（HD-ND）严重认知障碍的患者。此分类基于先前验证的HD PD-CRS截止评分。通过基于灰质体积体素的形态学（GMV-VBM）和皮质厚度（Cth）研究了各组脑萎缩的差异。使用体素和顶点一般线性模型来评估组比较，以控制年龄，性别，教育程度，CAG重复长度和运动症状严重程度的影响。生存率p <0.05的聚类和家庭误差校正（FWE）被认为具有统计学意义。为了表征观察到的各组大脑差异对认知能力的影响，

结果

所有组的社会人口统计学特征相似，HD组的CAG重复长度没有显着差异。与HC相比，两个HD组在多个皮质下和顶叶脑区域均表现出明显的萎缩。但是，与HC和HD-ND组相比，HD-Dem患者表现出更明显的GMV减少和皮质变薄的模式。重要的是，这种变薄仅限于顶颞叶和枕叶皮质区域。此外，这些大脑的改变还与评估额执行区和注意力区以及记忆，语言和建构能力的任务中较差的认知表现有关。

结论

HD痴呆患者的主要认知障碍与脑部和认知改变有关，超出了HD常见的典型额叶执行力缺陷。MRI所观察到的后皮质损伤及其与记忆，语言和内脏功能障碍的关系表明，纹状体外萎缩严重参与了HD患者的严重认知功能障碍。至关重要的是，该样本中的主要认知障碍与CAG重复长度，年龄或受教育程度无关。这一发现可能支持其他神经病理学机制可能加重HD的认知退化。