We thank Dr. Mahla for his interest in our work and for highlighting some of the important details of our analysis. While the high risk of developing Alzheimer’s disease (AD) in those with Down syndrome (DS) is well known [1], resulting in DS being the most common genetic cause of AD, those with DS have largely been excluded from clinical treatment trials for AD to date [2]. This is in part because of uncertainties regarding the time course of cognitive decline in AD in DS. Such trials are vitally important for the population with DS, given that the majority of adults with DS who die over the age of 36 have a diagnosis of dementia [3]. Our study aimed to address these uncertainties using a validated cognitive test battery [4], and we used our results to estimate sample sizes required to detect significant treatment effects for randomized controlled trials (RCTs) to delay dementia-related decline [5]. First, regarding the issue of how many of our participants already hadAD, our total sample included 56 individuals with a clinical diagnosis of dementia. As would be expected, the prevalence of clinically diagnosed dementia increased with age, and so the number of individuals with clinical dementia increased as the age groups became older (see Table 1 in [5] for the breakdown of age groups by dementia status). For the sample size calculations, individuals with a clinical diagnosis of dementia were excluded from the younger age groups (i.e., 36–40 years and 46–50 years) because such individuals would be ineligible for an RCT to assess decline before dementia diagnosis. The older age groups included individuals with dementia where relevant; these totals were 2 in the 41–45 year age group and 16 in the 51–55 year age group. Second, we used two different outcome measures for the sample size calculations as we had aimed to estimate sample sizes needed for two separate RCTs: firstly to delay decline 10–15 years before the mean age of dementia diagnosis (i.e., with a trial entry age of 36–40 years), and secondly to delay decline around the mean age of dementia diagnosis (i.e.,

中文翻译：

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回复“唐氏综合症认知标志物在阿尔茨海默病和痴呆症管理中的意义”

我们感谢 Mahla 博士对我们的工作感兴趣并强调了我们分析的一些重要细节。虽然唐氏综合症 (DS) 患者患阿尔茨海默病 (AD) 的高风险众所周知 [1]，导致 DS 是 AD 最常见的遗传原因，但 DS 患者在很大程度上已被排除在临床治疗试验之外公元至今[2]。这部分是因为 DS 中 AD 认知能力下降的时间过程存在不确定性。鉴于大多数 36 岁以上死亡的 DS 成人诊断为痴呆 [3]，此类试验对于 DS 人群至关重要。我们的研究旨在使用经过验证的认知测试组合来解决这些不确定性 [4]，我们使用我们的结果来估计检测随机对照试验 (RCT) 的显着治疗效果所需的样本量，以延迟痴呆相关的衰退 [5]。首先，关于我们有多少参与者已经患有 AD 的问题，我们的总样本包括 56 名临床诊断为痴呆症的人。正如预期的那样，临床诊断出的痴呆症的患病率随着年龄的增长而增加，因此患有临床痴呆症的人数随着年龄组的增长而增加（参见 [5] 中的表 1，了解按痴呆症状态划分的年龄组）。对于样本量计算，临床诊断为痴呆的个体被排除在较年轻的年龄组（即 36-40 岁和 46-50 岁）之外，因为这些个体没有资格进行 RCT 以评估痴呆诊断前的衰退。老年组包括相关的痴呆症患者；这些总数在 41-45 岁年龄组中为 2 人，在 51-55 岁年龄组中为 16 人。其次，我们使用两种不同的结果测量来计算样本量，因为我们的目的是估计两个独立 RCT 所需的样本量：首先，在痴呆症诊断的平均年龄之前 10-15 年延迟下降（即试验进入年龄36-40 岁），其次延迟痴呆诊断平均年龄的下降（即，