Predictive analytics for cognitive decline and Alzheimer’s disease

项目总结/摘要 阿尔茨海默病（AD）是老年人痴呆症的最常见原因，是全球主要的疾病之一。 医疗负担。然而，对于AD仍然没有有效的疾病改善疗法， 旨在预防或稳定认知损害的临床试验基本上失败了。 临床实践和研究中的决策高度依赖于实际预测 工具，可以有效地预测个人的认知或功能结果。这样的模型 可以潜在地用于临床研究，通过招募 在试验期间最有可能显示疾病进展的参与者。 或者，这些模型可以用来识别那些从 一级或二级预防，一旦有有效的治疗AD。本课题 目的是提供一个框架，用于实际预测认知衰退与衰老和前驱期 AD，通过将新的ML框架应用于多个维度的数据（人口统计学，遗传风险 评分、神经心理学测量、结构MRI和淀粉样蛋白成像）。我们的最终目标是 为了达到一个新的“衰老和AD的机器学习预测框架”（ML4AD），包括 每一个维度都将为预测模型增加增量值，因此 提高预测模型的性能，同时保持研究的成本和负担 至少是这样这个指导病人导向职业发展奖的候选人 (K23)Ali Ezzati博士是一名神经学家，他的职业目标是开发预测工具， 认知老化和痴呆症的研究和临床决策。拟议研究 将利用从几个正在进行的国际研究中获得的丰富的临床和生物标志物数据集， 研究，但也将为候选人提供一个独特的调查途径。候选人的 职业发展将受益于优秀人才的密切指导和科学指导 衰老/AD神经生物学研究人员（Lipton博士），机器学习和计算 神经科学（Davatzikos博士）和生物统计学（Hall博士）。这项研究的结果将告知 未来的二级预防试验，其中早期AD的敏感指标将是必要的， 识别高风险受试者并跟踪早期临床衰退。这项工作将作为基础 推进独立研究，重点是开发AD的预测工具， 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，认知神经病学， 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