Niroshan Jeyakumar, Sarah N Hilmer, Armando Teixeira-Pinto, Clement T Loy
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We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and \"residual\" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects.</p><p><strong>Results: </strong>Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03).</p><p><strong>Conclusions: </strong>The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"355-361"},"PeriodicalIF":2.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.\",\"authors\":\"Niroshan Jeyakumar, Sarah N Hilmer, Armando Teixeira-Pinto, Clement T Loy\",\"doi\":\"10.3233/JHD-230572\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia.</p><p><strong>Objective: </strong>We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset.</p><p><strong>Methods: </strong>We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and \\\"residual\\\" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects.</p><p><strong>Results: </strong>Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). 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引用次数: 0
摘要
背景:超过三分之一的亨廷顿舞蹈病发病年龄变异是由CAG重复序列长度无法解释的。在阿尔茨海默病中,虚弱在一定程度上调节了神经病理学和痴呆之间的关系。目的:我们研究反映亨廷顿病非遗传因素的多结构域脆性指数是否同样调节CAG重复序列长度与发病年龄之间的关系。方法:我们创建了一个评估合并症、药物滥用、多种用药和教育程度的脆弱指数。我们应用多元线性回归模型对2,741例明显亨廷顿舞蹈病患者进行研究,其中包括729例迟发性(60岁后)疾病患者,使用衰弱指数或组成项目评分和CAG重复序列长度作为自变量。我们使用实际发病年龄和“剩余”发病年龄(实际发病年龄和基于cag的预测发病年龄之间的差异)作为因变量,后者抵消了老年受试者累积合并症的可用时间增加。结果:在晚发亚组中,较高的衰弱指数评分与较低的剩余发病年龄显著相关(p = 0.03),尽管影响很小(以衰弱为预测因子的R2 = 0.27,而不以衰弱为预测因子的R2 = 0.26)。在晚发亚组中,合并症的数量也与较低的剩余发病年龄相关(p = 0.04)。药物滥用和吸烟与全队列早发年龄(p < 0.01, p = 0.02)和晚发亚组(p < 0.01, p = 0.03)显著相关。结论:在亨廷顿舞蹈病中,非遗传因素对发病年龄的影响,使用衰弱指数或单独评估是有限的。
Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.
Background: Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia.
Objective: We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset.
Methods: We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and "residual" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects.
Results: Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03).
Conclusions: The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.