Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatient Department 2, Western General Hospital, University of Edinburgh, Edinburgh, UK.
Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatient Department 2, Western General Hospital, University of Edinburgh, Edinburgh, UK.
Lancet Healthy Longev. 2022 Nov;3(11):e797-e803. doi: 10.1016/S2666-7568(22)00219-7.
Both research and clinical practice have traditionally centred on the dementia syndrome of Alzheimer's disease rather than its preclinical and prodromal stages. However, there is a strong scientific and ethical impetus to shift focus to earlier disease stages to improve brain health outcomes and help to keep affected individuals symptom-free (dementia-free) for as long as possible. We provide an overview of recent advancements in early detection, drug development, and trial methodology that should be utilised in the development of new therapies for use in brain health clinics. We propose a triad approach to Alzheimer's disease clinical trials, encompassing (1) experimental medicine studies to gather greater knowledge of disease mechanisms, (2) a more comprehensive platform of phase 2 learning trials to inform phase 3 confirmatory trials, and (3) precision medicine involving smaller subgroups of patients with shared characteristics. This triad would ensure that treatment targets are identified accurately, trial methodology focuses on at-risk populations, and sensitive outcome measures capture potential treatment effects. Clinical services around the world must embrace the brain health clinic model so that neurodegenerative diseases can be detected in their earliest phase to quicken drug development pipelines and potentially improve prognosis.
传统上，研究和临床实践都集中在阿尔茨海默病的痴呆综合征上，而不是其临床前和前驱阶段。然而，将重点转移到早期疾病阶段以改善大脑健康结果并帮助受影响的个体尽可能长时间保持无症状（无痴呆），具有强烈的科学和伦理推动力。我们提供了对早期检测、药物开发和试验方法学的最新进展的概述，这些进展应在开发用于大脑健康诊所的新疗法中得到利用。我们提出了阿尔茨海默病临床试验的三联方法，包括（1）实验医学研究以更深入地了解疾病机制，（2）更全面的 2 期学习试验平台，为 3 期确证试验提供信息，以及（3）涉及具有共同特征的较小亚组患者的精准医学。这种三联方法将确保准确识别治疗靶点，试验方法侧重于高危人群，并使用敏感的结果测量来捕捉潜在的治疗效果。世界各地的临床服务必须采用大脑健康诊所模式，以便在疾病的最早阶段发现神经退行性疾病，从而加快药物开发管道，并有可能改善预后。
