Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK.
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK.
Alzheimers Dement. 2019 Feb;15(2):245-257. doi: 10.1016/j.jalz.2018.08.009. Epub 2018 Nov 28.
Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes.
We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia.
Changes in memory and attention measures were most sensitive to early decline. Resulting sample size calculations for randomized controlled trials to detect significant treatment effects to delay decline were modest.
Our findings address uncertainties around the development of randomized controlled trials to delay cognitive decline in DS. Such trials are essential to reduce the high burden of dementia in people with DS and could serve as proof-of-principle trials for some drug targets.
唐氏综合征（DS）几乎普遍伴有阿尔茨海默病。因此，对于预防或延缓认知能力下降的随机对照试验来说，DS 患者是一个重要的群体，不过，了解认知早期变化的时间进程至关重要。
我们对 312 名 DS 成年人进行了迄今为止最大规模的认知研究，以评估从临床前期到前驱期痴呆，以及前驱期到临床期痴呆的进展过程中与年龄相关和与阿尔茨海默病相关的认知变化。
记忆和注意力测量的变化对早期下降最敏感。为了检测到延缓下降的显著治疗效果，针对随机对照试验进行的样本量计算适中。
我们的研究结果解决了有关延迟 DS 认知能力下降的随机对照试验发展的不确定性。此类试验对于降低 DS 患者的痴呆高负担至关重要，并且可以作为一些药物靶点的原理验证试验。
