Baksh R Asaad, Strydom André, Carter Ben, Carriere Isabelle, Ritchie Karen
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, and Neuroscience King's College London Denmark Hill London UK.
The LonDownS Consortium Denmark Hill London UK.
Alzheimers Dement (Amst). 2024 Mar 7;16(1):e12563. doi: 10.1002/dad2.12563. eCollection 2024 Jan-Mar.
Age is the greatest risk factor for Alzheimer's disease (AD). A limitation of randomized control trials in AD is a lack of specificity in the age ranges of participants who are enrolled in studies of disease-modifying therapies. We aimed to apply Emax (i.e., maximum effect) modeling as a novel approach to identity ideal treatment windows.
Emax curves were fitted to longitudinal cognitive data of 101 participants with AD and 1392 healthy controls. We included the Mini-Mental State Examination (MMSE) and tests of verbal fluency and executive functioning.
In people with AD, the earliest decline in the MMSE could be detected in the 67-71 age band while verbal fluency declined from the 41-45 age band. In healthy controls, changes in cognition showed a later trajectory of decline.
Emax modeling could be used to design more efficient trials which has implications for randomized control trials targeting the earlier stages of AD.
年龄是阿尔茨海默病（AD）最大的风险因素。AD随机对照试验的一个局限性在于，参与疾病修饰疗法研究的参与者年龄范围缺乏特异性。我们旨在应用Emax（即最大效应）模型作为一种新方法来确定理想的治疗窗口。
将Emax曲线拟合到101名AD患者和1392名健康对照者的纵向认知数据。我们纳入了简易精神状态检查表（MMSE）以及语言流畅性和执行功能测试。
在AD患者中，MMSE最早的下降可在67 - 71岁年龄组中检测到，而语言流畅性从41 - 45岁年龄组开始下降。在健康对照者中，认知变化显示出较晚的下降轨迹。
Emax模型可用于设计更有效的试验，这对针对AD早期阶段的随机对照试验具有重要意义。
