Département d'Études Cognitives, École Normale Supérieure, PSL University, Paris, 75005, France.
Faculté de Médecine, Université Paris-Est Créteil, Créteil, 94000, France.
Ann Clin Transl Neurol. 2024 Jul;11(7):1930-1941. doi: 10.1002/acn3.52120. Epub 2024 Jun 10.
Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. Our aim here was to identify factors that can be modified to slow disease progression even before the first symptoms appear.
We included 2636 presymptomatic individuals (comparison with family controls) drawn from the prospective observational cohort Enroll-HD, with more than 35 CAG repeats and at least two assessments of disease progression measured with the composite Huntington's disease rating Scale (cUHDRS). The association between sociodemographic factors, health behaviors, health history, and cUHDRS trajectory was assessed with a mixed-effects random forest using partial dependence plots and Shapley additive explanation method.
Participants were followed by an average of 3.4 (SD = 1.97) years. We confirmed the negative impact of age and a high number of CAG repeats. We found that a high level of education, a body mass index (BMI) <23 kg/m before the age of 40 and >23 kg/m thereafter, alcohol consumption of <15 units per week, current coffee consumption and no smoking were linked to slow disease progression, as did no previous exposure to antidepressants or anxiolytic, no psychiatric history or comorbidities, and being female. Other comorbidities or marital status showed no major association with HD evolution.
Reducing modifiable risk factors for HD is one way to support the presymptomatic population. A high level of education, low-to-moderate alcohol consumption, no smoking, and BMI control are likely to slow disease progression in this population.
亨廷顿病（HD）是一种神经退行性疾病，其特征为进行性运动、认知和精神症状。我们的目的是确定可以改变的因素，即使在出现第一个症状之前也能减缓疾病的进展。
我们纳入了来自前瞻性观察队列 Enroll-HD 的 2636 名无症状个体（与家族对照比较），这些个体具有超过 35 个 CAG 重复和至少两次使用综合亨廷顿病评定量表（cUHDRS）测量的疾病进展评估。使用混合效应随机森林，结合部分依赖图和 Shapley 加法解释方法，评估了社会人口因素、健康行为、健康史与 cUHDRS 轨迹之间的关联。
参与者平均随访 3.4（SD=1.97）年。我们证实了年龄和 CAG 重复数较多的负面影响。我们发现，较高的教育水平、40 岁前 BMI<23kg/m2 且此后 BMI>23kg/m2、每周饮酒量<15 单位、当前咖啡摄入量和不吸烟与疾病进展缓慢有关，以前未接触过抗抑郁药或抗焦虑药、无精神病史或合并症以及女性也是如此。其他合并症或婚姻状况与 HD 演变无明显关联。
降低 HD 的可改变风险因素是支持无症状人群的一种方法。在该人群中，高教育水平、低至中度饮酒量、不吸烟和 BMI 控制可能会减缓疾病的进展。
