Predictive analytics for cognitive decline and Alzheimer’s disease

项目摘要/摘要 阿尔茨海默病(AD)是导致老年人痴呆的最常见原因，是全球主要的 医疗负担。然而，目前仍没有有效的疾病调节疗法来治疗AD和 旨在预防或稳定认知障碍的临床试验在很大程度上失败了。 临床实践和研究的决策都高度依赖于实际预测 工具，它可以有效地预测个体的认知或功能结果。这样的模型 可以潜在地用于临床研究，通过登记来提高试验的力量 在试验的时间范围内最有可能表现出疾病进展的参与者。 或者，这些模型可以用来确定哪些人将受益于 一旦AD有了有效的治疗方法，就可以进行一级或二级预防。在这个项目中，我们 目的为认知功能衰退随年龄增长和前驱症状的预测提供一个实用的框架 AD，通过将新的ML框架应用于多维数据(人口统计学、遗传风险 评分、神经心理测量、结构核磁共振和淀粉样蛋白成像)。我们的最终目标是 为达到一个新的“机器学习衰老和AD预测框架”(ML4AD)，包括 每个维度都将为预测模型增加增量价值，因此 在保持研究成本和负担的同时提高预测模型的性能 至少是这样。以病人为导向的职业发展指导奖候选人 (K23)，Ali Ezzati博士是一位神经学家，他的职业目标是开发预测工具来帮助 认知老化和痴呆的研究和临床决策。拟议的研究 将利用几个正在进行的国际组织提供的丰富的临床和生物标记物数据集 学习，但也将为候选人提供一个独特的调查途径。候选人的 职业发展将受益于杰出人才的密切指导和科学指导 衰老/阿尔茨海默病神经生物学(利普顿博士)、机器学习和计算领域的研究人员 神经科学(达瓦茨科斯博士)和生物统计学(霍尔博士)。这项研究的发现将告诉我们 未来的二级预防试验，其中早期AD的敏感指标将是必要的 确定高危受试者并跟踪早期临床下降。这项工作将作为基础 在专注于AD和AD预测工具开发的独立研究中取得进展 相关的神经退行性疾病。 关键词：阿尔茨海默病，痴呆，轻度认知障碍，认知神经学 人工智能、机器学习、预测分析、纵向队列、大数据

Project Summary/Abstract Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a major global healthcare burden. However, there is still no effective disease modifying therapy for AD and clinical trials with the aim of preventing or stabilizing cognitive impairment have largely failed. Decision making in both clinical practice and research is highly dependent on practical predictive tools, which can effectively predict cognitive or functional outcomes in individuals. Such models could be potentially used in clinical research to boost the power of trials by enrollment of participants who are most likely to show disease progression during the trial’s timeframe. Alternatively, these models could be used to identifying individuals who would benefit from primary or secondary prevention once there are effective treatments for AD. In this project, we aim to provide a framework for practical prediction of cognitive decline with aging and prodromal AD, by applying a novel ML framework to multiple dimensions of data (demographics, genetic risk scores, neuropsychological measures, structural MRI, and amyloid imaging). Our ultimate goal is to arrive at a new “Machine Learning predictive framework for aging and AD” (ML4AD), comprised of dimensions each of which each will add incremental value to the predictive models, hence increasing the performance of predictive models while keeping the costs and burden of research at a minimum. The candidate for this Mentored Patient-Oriented Career Development Award (K23), Dr. Ali Ezzati, is a Neurologist whose career goal is to develop predictive tools to help research and clinical decision making in cognitive aging and dementia. The proposed research will leverage the rich clinical and biomarker dataset available from several ongoing international studies, but will also provide a unique avenue of investigation for the candidate. The candidate's career development will benefit from close mentorship and scientific guidance of outstanding investigators in aging/AD neurobiology (Dr. Lipton), machine learning and computational neuroscience (Dr. Davatzikos), and biostatistics (Dr. Hall). The findings from this study will inform future secondary prevention trials, in which sensitive indicators of early AD will be necessary to identify high-risk subjects and track early clinical decline. This work will serve as the foundation to move forward in independent research focusing on development of predictive tools in AD and related neurodegenerative disorders. Key words: Alzheimer’s Disease, Dementia, Mild Cognitive Impairment, Cognitive neurology, Artificial Intelligence, Machine Learning, Predictive Analytics, Longitudinal Cohort, Big Data