Although Huntington's disease (HD) has classically been viewed as an autosomal-dominant inherited neurodegenerative motor disorder, cognitive and/or behavioral changes are predominant and often an early manifestation of disease. About 40% of individuals in the presymptomatic period of HD meet the criteria for mild cognitive impairment, later progressing to dementia. The heterogenous spectrum of cognitive decline is characterized by deficits across multiple domains, particularly executive dysfunctions, but the underlying pathogenic mechanisms are still poorly understood. Investigating the pathophysiology of cognitive changes may give insight into important and early neurodegenerative events. Multimodal imaging revealed circuit-wide gray and white matter degenerative processes in several key brain regions, affecting prefronto-striatal/cortico-basal ganglia circuits and many other functional brain networks. Studies in transgenic animal models indicated early synaptic dysfunction, deficient neurotrophic transport and other molecular changes contributing to neuronal death. Synaptopathy within the cerebral cortex, striatum and hippocampus may be particularly important in mediating cognitive and neuropsychiatric manifestations of HD, although many other neuronal systems are involved. The interaction of mutant huntingtin protein (mHTT) with tau and its implication for cognitive impairment in HD is a matter of discussion. Further neuroimaging and neuropathological studies are warranted to better elucidate early pathophysiological mechanisms and to develop validated biomarkers to detect patients' cognitive status during the early stages of the condition significantly to implement effective preventing or management strategies.

尽管亨廷顿病（HD）传统上被视为一种常染色体显性遗传性神经退行性运动障碍，但认知和/或行为改变是主要的，并且通常是疾病的早期表现。大约 40% 的 HD 症状前期患者符合轻度认知障碍的标准，随后进展为痴呆。认知能力下降的异质谱的特点是跨多个领域的缺陷，特别是执行功能障碍，但其潜在的致病机制仍然知之甚少。研究认知变化的病理生理学可能有助于深入了解重要的早期神经退行性事件。多模态成像揭示了几个关键大脑区域的全回路灰质和白质退化过程，影响前额纹状体/皮质基底神经节回路和许多其他功能性大脑网络。转基因动物模型的研究表明，早期突触功能障碍、神经营养运输缺陷和其他导致神经元死亡的分子变化。尽管许多其他神经系统也参与其中，但大脑皮层、纹状体和海马内的突触病变对于介导 HD 的认知和神经精神表现可能特别重要。突变型亨廷顿蛋白 (mHTT) 与 tau 蛋白的相互作用及其对 HD 认知障碍的影响是一个值得讨论的问题。需要进一步的神经影像学和神经病理学研究，以更好地阐明早期病理生理机制，并开发经过验证的生物标志物来检测患者在疾病早期阶段的认知状态，以实施有效的预防或管理策略。