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）：人口人群表明，随着年龄相关痴呆症的预期急剧增加，公共卫生危机正在迫在眉睫。当前的重点是预防疾病，重点是表达某些认知障碍的老年人。我们建议识别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定义这些受损状态，如何考虑反向过渡，如何通过使用独特的统计（Markov）模型来区分发生率和发生率。但是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。没有单一的阿尔茨海默氏病中心（ADC）或合作研究具有足够的样本量，可以可靠地跟踪到痴呆症的过渡，并将阿尔茨海默氏病（AD）与包括血管痴呆（VAD）和Lewy身体病（LBD）的其他普遍脑疾病区分开。该项目将汇集来自六个良好建立的纵向人群的数据，以确定（1）符合不同类型痴呆症和MCI神经病理学标准的人（1）保存完整认知的风险因素，以及（2）特定形式的痴呆症（临床和神经病理学）。尽管存在神经病理学，但这将提高我们对中间受损状态和促进临床症状抗性的因素的理解。这些考虑因素导致以下具体目标。具体目的1：合并六个大型项目的数据库，这些项目遵循群体的痴呆症患者的群体，以进行严格的，统计，生物学上的分析，这些分析强调了纵向随访：肯塔基大学（肯塔基大学），修女研究（Nununnunnun of Mines of Minnesota University of Minnesota of Agania of Aganii nonii nonii nonii nonii ogiai og ogiai ogiai nii ogaakini ogiai og u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u u） （ROS，Rush医科大学）和OHSC ADC（俄勒冈州健康与科学大学）。该数据库将被公开访问。具体目的2：根据对这些中心收集的数据的认知和功能技能的定期评估，确定完整认知和痴呆之间的适当中间状态。特定目的3：研究使用新型统计方法研究过渡和相关的风险因素（例如，遗传，医学，在状态下处于受损状态的时间）。特定目的4：标准化数据库之间的神经病理学发现（包括定量神经病理评估），以实现对结局的新型致病决定因素的分析。这个目的使我们能够评估实际的脑病理学（例如，微吸收，路易尸体，海马硬化症和混合病理学）与参加尸检的参与者子集中的反典型状态有关。该目标可以支持痴呆症和临床前痴呆疾病中当前神经病理和临床研究诊断标准的拟议修订。