Achenbach Jannis, Stodt Benjamin, Saft Carsten
Department of Neurology, Huntington Center North Rhine-Westphalia, St. Josef-Hospital Bochum, Ruhr-University Bochum, Gudrunstraße 56, 44791 Bochum, Germany.
Leibniz Research Center for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Ardeystraße 67, 44139 Dortmund, Germany.
Biomedicines. 2023 Dec 17;11(12):3336. doi: 10.3390/biomedicines11123336.
: The Total Functional Capacity (TFC) score is commonly used in Huntington's disease (HD) research. The classification separates each disease stage (1-5), e.g., as an inclusion criterion or endpoint in clinical trials accepted by the Food and Drug Administration (FDA). In addition to the quantification of age- and CAG-repeat-dependent effects as well as interacting effects of both on the TFC, we aimed to investigate factors influencing the TFC, such as neuropsychiatric, educational, and cognitive disease burden using data from the largest HD observational study to date. In addition, we analyzed data from pre-manifest stages to investigate the influence of the above-mentioned factors on the TFC in that stage. A moderated regression analysis was conducted to analyze the interaction effects of age and CAG-repeat length on the TFC in HD patients. A simple slope analysis was calculated to illustrate the effects. Depending on TFC results, motor-manifest patients were grouped into five stages. Data from pre-manifest participants were analyzed with regard to years to onset and CAP scores. We identified = 10,314 participants as manifest HD. A significant part of variance on the TFC was explained by age ( = 0.029, (1;10,281) = 308.02, < 0.001), CAG-repeat length (∆ = 0.132, ∆ (1;10,280) = 1611.22, < 0.001), and their interaction (∆ = 0.049, ∆ (1;10,279) = 634.12, < 0.001). The model explained altogether 20.9% of the TFC score's variance ( = 907.60, < 0.001). Variance of psychiatric and cognitive symptoms significantly differed between stages. Exploratory analysis of median data in pre-manifest participants revealed the highest scores for neuropsychiatric changes between 5 to <20 years from the disease onset. TFC is mainly explained by the neurobiological factors, CAG-repeat length, and age, with subjects having more CAG-repeats showing a faster decline in function. Our study confirms TFC as a robust measure of progression in manifest HD.
总功能能力（TFC）评分常用于亨廷顿舞蹈病（HD）研究。该分类将每个疾病阶段（1 - 5期）区分开来，例如，作为美国食品药品监督管理局（FDA）认可的临床试验中的纳入标准或终点。除了量化年龄和CAG重复序列依赖性效应以及两者对TFC的相互作用效应外，我们旨在利用来自迄今为止最大规模的HD观察性研究的数据，调查影响TFC的因素，如神经精神、教育和认知疾病负担。此外，我们分析了症状前阶段的数据，以研究上述因素在该阶段对TFC的影响。进行了调节回归分析，以分析年龄和CAG重复序列长度对HD患者TFC的相互作用效应。计算了简单斜率分析以说明效应。根据TFC结果，有运动症状的患者被分为五个阶段。对症状前参与者的数据按发病年限和CAP评分进行了分析。我们确定了10314名参与者为显性HD患者。TFC的显著部分变异可由年龄（β = 0.029，F(1;10281) = 308.02，p < 0.001）、CAG重复序列长度（ΔR² = 0.132，ΔF(1;10280) = 1611.22，p < 0.001）及其相互作用（ΔR² = 0.049，ΔF(1;10279) = 634.12，p < 0.001）来解释。该模型总共解释了TFC评分变异的20.9%（F = 907.60，p < 0.001）。精神和认知症状的变异在各阶段间存在显著差异。对症状前参与者中位数数据的探索性分析显示，从疾病发病起5至<20年期间神经精神变化得分最高。TFC主要由神经生物学因素、CAG重复序列长度和年龄来解释，CAG重复序列更多的受试者功能下降更快。我们的研究证实TFC是显性HD病情进展的可靠指标。
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