Cognitively Defined Alzheimer's Subgroups: Natural history, neuropathology, and life course ramifications

认知定义的阿尔茨海默病亚组：自然史、神经病理学和生命历程的影响

• 批准号: 10404979
• 负责人: Paul K Crane
• 金额: $ 72.43万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10404979
• 关键词: 3-Dimensional; Academic Medical Centers; Address; Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Artificial Intelligence; Atrophic; Autopsy; Brain; Brain imaging; Brain region; Caregivers; Clinic; Clinical; Cognition; Cognitive; Communities; Data; Data Analyses; Diagnosis; Economics; Evolution; Family Caregiver; Genetic; Goals; Guidelines; Heterogeneity; Image; Infrastructure; Investigation; Knowledge; Language; Late Onset Alzheimer Disease; Left; Life; Life Cycle Stages; MRI Scans; Malpractice; Measurement; Medical Records; Memory; Modality; Modeling; Natural History; Nerve Degeneration; Outcome; Pathologic; Pattern; Performance; Persons; Process; Research; Research Personnel; Resources; Sampling; Scanning; Scourge; Side; Slice; Slide; Staging; Structure; Subgroup; Supervision; Testing; Time; Visuospatial; Woman; base; cerebral atrophy; clinical heterogeneity; cognitive testing; cohort; deep learning; digital; disorder subtype; economic implication; executive function; hippocampal atrophy; improved; innovation; learning strategy; malignant breast neoplasm; medical specialties; neuroimaging; neuropathology; personalized medicine; precision medicine; programs; regional atrophy; regional difference; success; tau Proteins

Clinical heterogeneity is common in late-onset Alzheimer's disease (AD). This heterogeneity leads to the question of whether there are biologically distinct subsets of people with Alzheimer's disease. Precision medicine strategies can categorize people with a condition into subgroups and treat each subgroup differently to improve overall treatment success. Project 2 addresses whether cognitive data can be used to similarly categorize “Alzheimer's disease.” The investigators use cognitive testing data from the time of Alzheimer's diagnosis to define subgroups. They use scores from memory, executive functioning, language, and visuospatial functioning and compare those scores to each other. The modal pattern has all scores relatively similar to each other (AD-No Domains). There are four groups where scores in one domain are much worse than the other domains – AD-Memory, AD-Executive Functioning, AD-Language, and AD-Visuospatial. There are people who have multiple domains with worse scores (AD-Multiple Domains). The investigators have previously found important genetic, clinical, and imaging differences that correspond to these subgroups. The overall goal of Project 2 is to leverage Adult Changes in Thought (ACT) U19 Research Program resources to further scientific understanding of cognitively defined Alzheimer's disease subgroups. Specific Aims are: Aim 1. Define the evolution of regional brain atrophy across cognitively-defined subgroups. The investigators will leverage clinical MRI scans, research MRI scans including some obtained for this project, ex vivo scans, and 3D brain data derived from digital photographs of brain slices at autopsy. Aim 2. Determine neuropathological change across cognitively-defined subgroups. The investigators will leverage ACT's tremendous neuropathology resources, including extensive new sampling, digital slide scanning, and approaches that robustly quantify neuropathology findings including deep learning methods. Aim 3. Determine the clinical, functional, living situation, caregiver network, and economic ramifications of cognitively defined subgroups. The investigators will leverage ACT's infrastructure to collect data from extensive medical records, collect new data from people with Alzheimer's and their families and caregivers, and perform careful quantitative and qualitative analyses to determine whether there are differences across subgroups in clinical, functional, living situation, caregiver network, or economic implications. Taken together, these investigations will more firmly establish the implications of cognitively defined subgroups, furthering our progress towards personalized medicine approaches to ameliorate the scourge of Alzheimer's disease.

临床异质性在晚期阿尔茨海默氏病（AD）中很常见。这种异质性导致 是否有生物学上不同的阿尔茨海默氏病的人群。精确 医学策略可以将有条件的人分类为子组，并以不同的方式对待每个亚组 改善整体治疗成功。项目2解决了是否可以使用认知数据 分类为“阿尔茨海默氏病”。研究人员从阿尔茨海默氏时代开始使用认知测试数据 诊断以定义亚组。他们使用内存，执行功能，语言和 视觉功能并将这些分数彼此比较。模式模式的所有得分相对较高 彼此相似（AD-NO域）。有四组，一个域中的得分差得多 而不是其他领域 - 广告记忆，ad-dectectection，AD语言和ad-visuospatial。那里 是那些分数较差的人（广告域）。调查人员有 先前发现与这些亚组相对应的重要遗传，临床和成像差异。 项目2的总体目标是利用成人思想变化（ACT）U19研究计划资源 对认知定义的阿尔茨海默氏病亚组的进一步科学理解。具体目的是：目标1。 定义跨认知定义的亚组的区域脑萎缩的演变。调查人员会 利用临床MRI扫描，研究MRI扫描，其中包括该项目获得的一些，离体扫描和 3D大脑数据来自尸检时大脑切片的数字照片。目标2。确定神经病理学 跨认知定义的子组的变化。调查人员将利用行为的巨大 神经病理学资源，包括广泛的新样本，数字滑扫描以及该方法 坚固量化神经病理学的发现，包括深度学习方法。目标3。确定临床， 认知定义的亚组的功能，生活状况，护理人员网络和经济后果。这 调查人员将利用ACT的基础设施从广泛的医疗记录中收集数据，收集新数据 来自阿尔茨海默氏症及其家人和照料者的人，并进行仔细的定量和定性 分析以确定临床，功能，生活状况中亚组之间是否存在差异， 护理人员网络或经济影响。综上所述，这些投资将首先建立 认知定义的子组的含义，将我们迈向个性化医学的进步 改善阿尔茨海默氏病的祸害的方法。