Role of impaired cognitive states & risk factors in conversion to mixed dementias

认知状态受损的作用

• 批准号: 8890026
• 负责人: JEFFREY A KAYE
• 金额: $ 51.99万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8890026
• 关键词: Accounting; Age; Aging; Alzheimer' s Disease; Americas; Asia; Autopsy; Biological Markers; Biological Preservation; Brain Diseases; Brain Pathology; Caring; Clinical; Clinical Data; Clinical Research; Clinical assessments; Cognition; Cognitive; Cohort Studies; Communities; Complement; Complex; Consensus; Data; Databases; Dementia; Diagnostic; Disease; Elderly; Epidemiology; Evaluation; Funding; Gray unit of radiation dose; Health Care Costs; Health Sciences; Hippocampus (Brain); Impaired cognition; Incidence; Individual; Investigation; Kentucky; Lead; Lewy Bodies; Lewy Body Disease; Magnetic Resonance Imaging; Measures; Medical; Medical Genetics; Memory; Meta-Analysis; Minnesota; Modeling; Multicenter Studies; National Institute on Aging; Oregon; Outcome; Participant; Pathology; Patients; Population; Prevalence; Prevention strategy; Public Health; Registries; Religion and Spirituality; Research; Research Personnel; Resistance; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Sclerosis; Series; Statistical Methods; Statistical Models; Symptoms; Time; United States National Institutes of Health; Universities; Validation; Vascular Dementia; Washington; aging brain; base; cohort; cooperative study; cost; demographics; design; disorder prevention; experience; follow-up; improved; innovation; insight; markov model; meetings; mild cognitive impairment; mixed dementia; neuropathology; novel; pre-clinical; prevent; prevention clinical trial; skills; treatment strategy

DESCRIPTION (provided by applicant): Population demographics suggest that with the expected dramatic increase in age-associated dementias a public health crisis is looming. Current emphasis is on disease prevention with a focus on elderly individuals who express some cognitive impairment. We propose to identify authoritatively the risk and protective factors for cognitive decline in older persons. We have shown how to define these impaired states retrospectively, how to account for reverse transitions, how to distinguish prevalence from incidence, and how to account for competing risks by using a unique statistical (Markov) model. But sufficient longitudinal and neuropathological data is currently not available to distinguish among different types of dementia. No single Alzheimer's Disease Center (ADC) or cooperative study has an adequate sample size to reliably track transitions to dementia and differentiate Alzheimer's disease (AD) from other prevalent brain diseases that include vascular dementia (VaD) and Lewy body disease (LBD). This project will pool data from six well established longitudinal cohorts to identify risk factors for (1) preservation of intact cognition in those meeting neuropathological criteria for varying types of dementia and MCI and (2) specific forms of dementia (clinical and neuropathological). This will improve our understanding of intervening impaired states and factors that promote resistance to clinical symptoms despite the presence of neuropathology. These considerations lead to the specific aims below. Specific Aim 1: To merge databases from six large projects that follow cohorts of cognitively intact subjects to dementia, for the purpose of rigorous, statistical, biologically-informed analyses that accentuate longitudinal follow-up: BRAiNS (University of Kentucky), Nun Study (University of Minnesota), Memory and Aging Project (Washington U), Kuakini Honolulu-Asia Aging Study, Religious Orders Study (ROS, Rush Medical University), and the OHSC ADC (Oregon Health & Science University). The database would be made publicly accessible. Specific Aim 2: To identify appropriate intervening states between intact cognition and dementia based on periodic assessments of cognition and functional skills from data collected at these centers. Specific Aim 3: To study transitions and associated risk factors (e.g., genetic, medical, time in an impaired state) using novel statistical methods. Specific Aim 4: To standardize the neuropathological findings across databases (including quantitative neuropathological assessments) to enable the analysis of novel pathogenetic determinants of outcomes. This aim allows us to evaluate how actual brain pathology (e.g., microinfarcts, Lewy bodies, hippocampal sclerosis, and mixed pathologies) relates to antemortem states in the subset of participants coming to autopsy. This aim could support proposed revisions of current neuropathological and clinical research diagnostic criteria in dementia and preclinical dementia conditions.

描述（由申请人提供）：人口统计数据表明，随着与年龄相关的痴呆症的预期急剧增加，公共卫生危机迫在眉睫。目前的重点是疾病预防，重点是表现出一定认知障碍的老年人。我们建议权威地确定老年人认知能力下降的风险和保护因素。我们已经展示了如何回顾性地定义这些受损状态，如何解释反向转变，如何区分患病率和发病率，以及如何通过使用独特的统计（马尔可夫）模型来解释竞争风险。但目前尚无足够的纵向和神经病理学数据来区分不同类型的痴呆症。没有哪个阿尔茨海默病中心 (ADC) 或合作研究拥有足够的样本量来可靠地追踪痴呆症的转变，并将阿尔茨海默病 (AD) 与其他流行的脑部疾病（包括血管性痴呆 (VaD) 和路易体病 (LBD)）区分开来。该项目将汇集来自六个完善的纵向队列的数据，以确定以下风险因素：(1) 满足不同类型痴呆和 MCI 的神经病理学标准的人保留完整的认知；(2) 特定形式的痴呆（临床和神经病理学）。这将提高我们对干预性受损状态和促进对临床症状抵抗力的因素的理解，尽管存在神经病理学。这些考虑导致了以下具体目标。具体目标 1：合并来自六个大型项目的数据库，这些项目追踪认知完整的受试者群体至痴呆症，以进行严格的、统计的、生物学分析，强调纵向随访：BRAiNS（肯塔基大学）、Nun 研究（明尼苏达大学）、记忆与衰老项目（华盛顿大学）、Kuakini 檀香山亚洲老龄化研究、宗教秩序研究（ROS、拉什医科大学）以及OHSC ADC（俄勒冈健康与科学大学）。该数据库将可供公众访问。具体目标 2：根据这些中心收集的数据对认知和功能技能进行定期评估，确定完整认知和痴呆之间适当的干预状态。具体目标 3：使用新颖的统计方法研究转变和相关风险因素（例如遗传、医疗、受损状态的时间）。具体目标 4：标准化数据库中的神经病理学发现（包括定量神经病理学评估），以便能够分析结果的新发病决定因素。这一目标使我们能够评估实际的大脑病理学（例如，微梗死、路易体、海马硬化和混合病理学）与进行尸检的参与者的生前状态之间的关系。这一目标可以支持对当前痴呆症和临床前痴呆症神经病理学和临床研究诊断标准的拟议修订。