性别与亨廷顿病胞嘧啶-腺嘌呤-鸟嘌呤-年龄产物评分的相互作用：临床和神经影像学观点

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-09-23 DOI:10.1002/mds.70064

Jingwen Yao,Grayson Feng,Guowen Shao,Zexi Wang,Adys Mendizabal,Donatello Telesca,Kaiying Fang,Lola Ibragimova,Juwairia Shoaib,Melanie A Morrison,Janine M Lupo

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The disease exhibits sex-related differences in symptomatology and disease progression, but the effect on brain structural biomarkers and the interaction between sex and CAG-age product score (CAPS), a widely used index combining the effect of CAG expansion and age, remains underexplored.\r\n\r\nOBJECTIVE\r\nThe aim of this study was to investigate the interplay between sex and CAPS on clinical measures and neuroimaging biomarkers in HD.\r\n\r\nMETHODS\r\nWe retrospectively analyzed data from Enroll-HD, TRACK-HD/ON, PREDICT-HD, and IMAGE-HD studies, including a combined dataset of 19,738 participants with CAG ≥ 40. 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引用次数: 0

摘要

背景：亨廷顿氏病（HD）是一种进行性神经退行性疾病，由亨廷顿蛋白基因中胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复扩增引起。该疾病在症状和疾病进展方面表现出性别差异，但对脑结构生物标志物的影响以及性别与CAG-age product score （CAPS）之间的相互作用（CAPS是一种广泛使用的结合CAG扩展和年龄影响的指标）仍未得到充分研究。目的探讨性别与cap对HD患者临床指标和神经成像生物标志物的相互作用。方法回顾性分析来自Enroll-HD、TRACK-HD/ON、PREDICT-HD和IMAGE-HD研究的数据，包括一个合并的数据集，包括19,738名CAG≥40的参与者。在控制协变量的情况下，采用线性混合模型评估性别和性别- caps相互作用对临床评估的影响，包括统一HD评定量表（UHDRS）、UHDRS和问题行为评估，以及神经成像生物标志物（纹状体体积和皮质厚度）。结果随着CAPS的增加，女性受试者纹状体萎缩和皮质变薄的表现不明显（尾状核：β男性/女性$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -3.449/-2.931, P = 0.05；壳核：β男性/女性$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -4.770/-3.902, P < 0.01）。在临床指标方面，随着CAPS的增加，女性的运动能力下降（运动总分：β男/女$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = 3.008/3.230, P < 0.0001），认知能力下降（符号数字模式测试：β男/女$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -34.52/-38.57, P < 0.0001），功能下降（总功能容量：β男/女$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -6.413/-6.783, P < 0.05；独立量表：β男/女$$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -32.26/-34.85, P < 0.001）更严重。结论性别- caps相互作用显著影响HD的临床和神经影像学生物标志物，强调将性别特异性因素纳入HD的临床分期和管理的重要性。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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Interplay Between Sex and Cytosine-Adenine-Guanine-Age Product Score in Huntington's Disease: Clinical and Neuroimaging Perspectives.

BACKGROUND Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene. The disease exhibits sex-related differences in symptomatology and disease progression, but the effect on brain structural biomarkers and the interaction between sex and CAG-age product score (CAPS), a widely used index combining the effect of CAG expansion and age, remains underexplored. OBJECTIVE The aim of this study was to investigate the interplay between sex and CAPS on clinical measures and neuroimaging biomarkers in HD. METHODS We retrospectively analyzed data from Enroll-HD, TRACK-HD/ON, PREDICT-HD, and IMAGE-HD studies, including a combined dataset of 19,738 participants with CAG ≥ 40. Linear mixed models were employed to evaluate the influence of sex and the sex-CAPS interaction on clinical evaluations, including Unified HD Rating Scale (UHDRS) UHDRS and Problem Behaviors Assessment, and neuroimaging biomarkers (striatal volumes and cortical thickness), while controlling for covariates. RESULTS Female participants exhibited less pronounced striatal atrophy and cortical thinning with increasing CAPS (caudate: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -3.449/-2.931, P = 0.05; putamen: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -4.770/-3.902, P < 0.01). Regarding clinical measures, females experience greater motor decline with increasing CAPS (total motor score: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = 3.008/3.230, P < 0.0001), greater cognitive decline (symbol digit modalities test: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -34.52/-38.57, P < 0.0001), and greater functional decline (total functional capacity: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -6.413/-6.783, p < 0.05; Independence Scale: β male / female $$ {\beta}_{\mathrm{male}/\mathrm{female}} $$ = -32.26/-34.85, P < 0.001). CONCLUSIONS The sex-CAPS interaction significantly impacts both clinical and neuroimaging biomarkers of HD, underscoring the importance of incorporating sex-specific considerations into the clinical staging and management of HD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.