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: 10672371
• 负责人: Paul K Crane
• 金额: $ 76.16万
• 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/10672371
• 关键词: 3-Dimensional; Academic Medical Centers; Address; Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Artificial Intelligence; Atrophic; Autopsy; Braak' s hypothesis; Brain; Brain imaging; Brain region; Caregivers; Categories; Clinic; Clinical; Cognition; Cognitive; Communities; Data; Diagnosis; Economics; Evolution; Family; 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; Testing; Time; Visuospatial; Woman; 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.

临床异质性在晚发性阿尔茨海默病(AD)中很常见。这种异质性导致了 关于阿尔茨海默病患者是否存在生物学上不同的亚群的问题。精密度 医学策略可以将患有某种疾病的人分成不同的亚组，并对每个亚组进行不同的治疗 以提高整体治疗成功率。项目2解决了认知数据是否可以用来类似地 归类为“阿尔茨海默氏症”。研究人员使用的是阿尔茨海默氏症时期的认知测试数据 诊断以定义子组。他们使用记忆、执行功能、语言和 并将这些分数相互比较。情态模式的所有分数都是相对的 彼此相似(AD-没有域)。有四组人在一个领域的分数要差得多 而不是其他领域--AD-记忆、AD-执行功能、AD-语言和AD-视觉空间。那里 是拥有多个域名但得分较低的人(AD-多个域名)。调查人员已经 以前发现了与这些亚组相对应的重要的遗传、临床和影像差异。这个 项目2的总体目标是利用成人思维变化(ACT)U19研究计划资源来 对认知定义的阿尔茨海默病亚型的进一步科学理解。具体目标有：目标1. 定义跨认知定义的亚组的区域性脑萎缩的演变。调查人员将 利用临床核磁共振扫描，研究核磁共振扫描，包括为该项目获得的一些，体外扫描，以及 3D大脑数据来自尸检时脑片的数字照片。目的2.确定神经病理 跨认知定义的子组进行更改。调查人员将利用ACT的巨大优势 神经病理学资源，包括广泛的新采样、数字幻灯片扫描和 强有力地量化神经病理结果，包括深度学习方法。目的3.确定临床， 认知定义的亚群的功能、生活状况、照顾者网络和经济影响。这个 调查人员将利用ACT的基础设施从大量的医疗记录中收集数据，收集新的数据 从阿尔茨海默氏症患者及其家人和照顾者那里获得，并进行仔细的定量和定性 分析以确定不同亚组在临床、功能、生活状况、 照顾者网络，或经济影响。综上所述，这些调查将更坚定地确立 认知定义的亚群的含义，进一步推动我们向个性化医学的进展 改善阿尔茨海默氏症祸害的方法。