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.

临床异质性在晚发性阿尔茨海默病（AD）中很常见。这种异质性导致了 是否存在生物学上不同的阿尔茨海默病患者亚群的问题。精度 医学策略可以将患有某种疾病的人分成不同的小组，并对每个小组进行不同的治疗 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于类似的 归类为“阿尔茨海默病”研究人员使用了阿尔茨海默氏症时期的认知测试数据 诊断以确定亚组。他们使用记忆、执行功能、语言和 视觉空间功能，并将这些分数相互比较。情态模式的得分都是相对的 彼此相似（AD-无域）。有四个组在某个领域的得分更差 AD-记忆、AD-执行功能、AD-语言和AD-视觉空间。那里 有多个领域得分较低的人（AD-多个领域）。调查人员已 以前发现的重要的遗传，临床和影像学差异，对应于这些亚组。的 项目2的总体目标是利用U19研究项目的成人思想变化（ACT）资源， 进一步科学地理解认知定义的阿尔茨海默病亚组。具体目标是：目标1。 在认知定义的亚组中定义局部脑萎缩的演变。调查人员将 利用临床MRI扫描、研究MRI扫描（包括本项目获得的部分扫描）、离体扫描，以及 3D大脑数据来自尸检时大脑切片的数字照片。目标二。确定神经病理学 在认知定义的亚组之间的变化。调查人员将利用ACT的巨大 神经病理学资源，包括广泛的新采样，数字幻灯片扫描，和方法， 强大的量化神经病理学发现，包括深度学习方法。目标3。确定临床， 功能，生活状况，照顾者网络，和认知定义的亚组的经济后果。的 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， 从阿尔茨海默氏症患者及其家人和照顾者，并进行仔细的定量和定性 分析以确定亚组之间在临床、功能、生活状况， 护理人员网络或经济影响。综合起来，这些调查将更牢固地确立 认知定义的亚组的影响，促进我们向个性化医疗的进展 改善阿尔茨海默病的方法。