Clinical and Pathological Studies in the Oldest Old

最古老的临床和病理学研究

• 批准号: 7463369
• 负责人: CLAUDIA H. KAWAS
• 金额: $ 134.83万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463369
• 关键词: Activities of Daily Living; Age; Aged, 80 and over; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Anemia; Anterior; Autopsy; Biological; Blood Vessels; California; Centenarian; Clinical; Clinical Data; Cognition; Cognitive; Cohort Studies; Collaborations; DNA; Data; Dementia; Development; Diagnosis; Elderly; Exercise; Fiber; Funding; Future; Genetic; Goals; Health; Hippocampus (Brain); Hospitals; Impaired cognition; Incidence; Individual; Intervention; Intervention Studies; Investigation; Laboratory Study; Life; Measures; Memory impairment; Neurons; Nonagenarian; Other Genetics; Oxygen; Oxygen Therapy Care; Participant; Pathology; Pathology, Other; Pathway interactions; Pennsylvania; Performance; Population; Prefrontal Cortex; Principal Investigator; Prospective Studies; Public Health; Range; Rate; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Scientist; Societies; Speed; Standards of Weights and Measures; Surveys; Testing; Universities; Walking; age group; age related; aged; base; brain tissue; cingulate gyrus; density; disability; entorhinal cortex; frailty; functional decline; functional disability; functional loss; functional status; medical schools; member; modifiable risk; neuronal cell body; prevent; programs; prospective; research study; sex; size; synuclein; tau Proteins; tau-1

DESCRIPTION (provided by applicant): Project Summary Initiated in 2003, the goal of The 90+Study is to perform prospective clinical, pathological, and genetic investigations in a population based sample of people aged 90 years and older. With a wealth of cognitive tests, laboratory studies, physical performance measures, genetic and other data in The 90+ Study, plus survey information collected on these individuals since 1981 as part of the Leisure World Cohort Study, we will estimate incidence rates and evaluate risk and protective factors for dementia (Aim 1), functional disability and frailty (Aim 2), as well as cognitive and functional decline in the oldest old (Aim 3). Our studies emphasize potentially modifiable factors (oxygen saturation, anemia, and physical performance) as risk factors for dementia and disability in this age group, and could potentially provide the basis for future intervention studies in the oldest old. Based on our preliminary studies, we hypothesize that poor arterial oxygen saturation is a risk factor for cognitive decline and dementia, while anemia and physical performance measures (such as walk speed and handgrip) are risk factors for the development of disability, frailty, and functional decline in demented and non demented individuals. Half of all demented subjects in this age range do not have significant classical AD or other pathologies to explain cognitive loss. In this application, new collaborations enhance our clinical pathological studies investigating the biological correlates of cognition in the oldest old (Aim 4). Brain tissues from our well characterized subjects will be studied by investigators at the University of California, Irvine, University of Pennsylvania, and Johns Hopkins School of Medicine as we test our hypotheses that soluble, rather than insoluble, oligomeric species of A2, tau and 1 synuclein may be responsible for cognitive loss in 90+ year olds (Aim 4b) and that non AD pathologies, relevant to neuronal integrity and circuits, may contribute to cognitive loss through other age related mechanisms (Aim 4c). Finally, we will develop our clinical data and biological samples (brain tissues and DNA) as a resource to be actively shared with scientists worldwide. Project Narrative Understanding factors that influence the cognitive and functional status of the most senior members of our society is a major goal of this proposal. In our prospective studies of dementia, disability, and frailty in the oldest old, we will investigate the relationship to dementia, disability, and frailty of arterial O2 saturation, anemia, physical performance measures, and other factors that might be amenable to intervention. Ultimately our goal is to find ways to extend life without disability in nonagenarians and centenarians. If low O2 saturation, anemia or poor physical performance is associated with increased risk of dementia or disability in exceptionally long life, it would provide the basis for experimental studies to determine if oxygen therapy, treatment of anemia, or exercise could prevent or delay the loss of cognition and activities of daily living in the oldest old. The potential public health implications are enormous for the fastest growing segment of our population. PUBLIC HEALTH RELEVANCE: Understanding factors that influence the cognitive and functional status of the most senior members of our society is a major goal of this proposal. In our prospective studies of dementia, disability, and frailty in the oldest-old, we will investigate the relationship to dementia, disability, and frailty of arterial O2 saturation, anemia, physical performance measures, and other factors that might be amenable to intervention. Ultimately our goal is to find ways to extend life without disability in nonagenarians and centenarians. If low O2 saturation, anemia or poor physical performance is associated with increased risk of dementia or disability in exceptionally long life, it would provide the basis for experimental studies to determine if oxygen therapy, treatment of anemia, or exercise could prevent or delay the loss of cognition and activities of daily living in the oldest-old. The potential public health implications are enormous for the fastest growing segment of our population.

描述（由申请人提供）： 项目摘要 90+ 研究于 2003 年启动，其目标是对 90 岁及以上人群的人群样本进行前瞻性临床、病理和基因调查。凭借《90+ 研究》中丰富的认知测试、实验室研究、身体机能测量、遗传和其他数据，以及自 1981 年以来作为休闲世界队列研究的一部分收集的这些个体的调查信息，我们将估计发病率并评估风险痴呆（目标 1）、功能障碍和虚弱（目标 2）以及老年人认知和功能衰退（目标 3）的保护因素。我们的研究强调潜在的可改变因素（氧饱和度、贫血和身体机能）是该年龄段痴呆和残疾的危险因素，并可能为未来针对老年人的干预研究提供基础。根据我们的初步研究，我们假设动脉血氧饱和度差是认知能力下降和痴呆的危险因素，而贫血和身体表现指标（例如步行速度和握力）是残疾、虚弱和功能障碍发展的危险因素。痴呆和非痴呆个体的减少。这个年龄段的所有痴呆症受试者中有一半没有明显的经典 AD 或其他病理学来解释认知丧失。在此应用中，新的合作增强了我们的临床病理学研究，调查老年人认知的生物相关性（目标 4）。加州大学欧文分校、宾夕法尼亚大学和约翰霍普金斯大学医学院的研究人员将研究来自我们已明确表征的受试者的脑组织，以检验我们的假设：A2、tau 和 1 的寡聚体是可溶性而非不可溶性的。突触核蛋白可能是导致 90 岁以上老年人认知丧失的原因（目标 4b），并且与神经元完整性和回路相关的非 AD 病理可能通过其他年龄相关机制导致认知丧失（目标 4c）。最后，我们将开发我们的临床数据和生物样本（脑组织和 DNA）作为与全世界科学家积极共享的资源。项目叙述 了解影响我们社会最高级成员认知和功能状态的因素是该提案的主要目标。在我们对老年人痴呆、残疾和虚弱的前瞻性研究中，我们将调查动脉氧饱和度、贫血、身体机能测量和其他可能需要干预的因素与痴呆、残疾和虚弱的关系。我们的最终目标是找到延长九十岁和百岁老人寿命且不致残疾的方法。如果低氧饱和度、贫血或身体机能不佳与超长寿命中痴呆或残疾的风险增加有关，那么这将为实验研究提供基础，以确定氧疗、贫血治疗或运动是否可以预防或延缓丧失老年人的认知和日常生活活动。对于我们人口增长最快的部分来说，潜在的公共卫生影响是巨大的。公共卫生相关性：了解影响我们社会最高级成员认知和功能状态的因素是该提案的主要目标。在我们对老年人痴呆、残疾和虚弱的前瞻性研究中，我们将调查动脉氧饱和度、贫血、身体机能测量和其他可能需要干预的因素与痴呆、残疾和虚弱的关系。我们的最终目标是找到延长九十岁和百岁老人寿命且不致残疾的方法。如果低氧饱和度、贫血或身体机能不佳与超长寿命中痴呆或残疾的风险增加有关，那么这将为实验研究提供基础，以确定氧疗、贫血治疗或运动是否可以预防或延缓丧失老年人的认知和日常生活活动。对于我们人口增长最快的部分来说，潜在的公共卫生影响是巨大的。