Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
The LonDownS Consortium, London, UK.
Alzheimers Dement. 2021 Apr;17(4):595-604. doi: 10.1002/alz.12222. Epub 2020 Nov 23.
People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).
Cohort study. Event-based and dose-response E models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease-modifying treatments that reduced decline by 35% or 75%.
Seventy-five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50-200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.
Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose-response models could help tailor future RCTs.
唐氏综合征（DS）患者通常在 40 岁之前就会出现阿尔茨海默病（AD）的神经病理学改变，但由于缺乏结局指标和纵向数据，他们无法被纳入随机对照试验（RCT）。
队列研究。基于事件的 E 模型和剂量反应 E 模型被用于纵向认知数据，以对 AD 进行分期并确定衰退的最早年龄。研究结果为假设性的、针对疾病修饰治疗的 RCT 提供了样本量估算依据，这些治疗可使衰退减少 35%或 75%。
75%的参与者在 AD 分期模型中进展或保持稳定；效应大小因年龄组和测试而异。使用敏感的认知结局指标，并针对 36 至 45 岁年龄段进行招募，那么在每只手臂招募 50-200 人时，就可以检测到不同的治疗效果。
使用敏感的结局指标来监测早期衰退，可在 DS 人群中进行有效的 AD 预防治疗 RCT。剂量反应模型可以帮助定制未来的 RCT。
