Movement disorders : official journal of the Movement Disorder Society · 2025
Interplay Between Sex and Cytosine-Adenine-Guanine-Age Product Score in Huntington's Disease: Clinical and Neuroimaging Perspectives.
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Yao Jingwen, Feng Grayson, Shao Guowen, Wang Zexi, Mendizabal Adys, Telesca Donatello, Fang Kaiying, Ibragimova Lola, Shoaib Juwairia, Morrison Melanie A, Lupo Janine M
Аннотация
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 = -3.449/-2.931, P = 0.05; putamen: β male / 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 = 3.008/3.230, P < 0.0001), greater cognitive decline (symbol digit modalities test: β male / female = -34.52/-38.57, P < 0.0001), and greater functional decline (total functional capacity: β male / female = -6.413/-6.783, p < 0.05; Independence Scale: β male / 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.
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 = -3.449/-2.931, P = 0.05; putamen: β male / 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 = 3.008/3.230, P < 0.0001), greater cognitive decline (symbol digit modalities test: β male / female = -34.52/-38.57, P < 0.0001), and greater functional decline (total functional capacity: β male / female = -6.413/-6.783, p < 0.05; Independence Scale: β male / 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.