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)：项目概要始于2003年，90多项研究的目标是在90岁及以上的人群样本中进行前瞻性的临床、病理和遗传学调查。根据90+研究中丰富的认知测试、实验室研究、体能测量、遗传和其他数据，加上自1981年以来作为休闲世界队列研究的一部分收集的关于这些人的调查信息，我们将估计痴呆症(目标1)、功能残疾和虚弱(目标2)以及最年长老年人的认知和功能衰退(目标3)的发病率，并评估风险和保护因素。我们的研究强调潜在的可改变因素(血氧饱和度、贫血和体能)是这一年龄段痴呆和残疾的危险因素，并可能为未来对高龄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低是认知能力下降和痴呆的危险因素，而贫血和体能测量(如行走速度和握手)是痴呆和非痴呆个体残疾、虚弱和功能下降的危险因素。在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阿尔茨海默病或其他病理疾病来解释认知障碍。在这一应用中，新的合作加强了我们的临床病理学研究，调查最年长老年人认知的生物学相关性(目标4)。来自我们特征良好的受试者的脑组织将由加州大学欧文分校、宾夕法尼亚大学和约翰霍普金斯大学医学院的研究人员进行研究，因为我们测试了我们的假设，即可溶而不是不可溶的A2、tau和1突触核蛋白的寡聚体可能导致90岁以上老年人的认知损失(目标4b)，以及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损失(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)，作为一种资源，积极与世界各地的科学家共享。项目叙述了解影响我们社会最高级成员的认知和功能状态的因素是这项提议的主要目标。在我们对高龄老人的痴呆症、残疾和虚弱的前瞻性研究中，我们将调查与痴呆症、残疾和动脉血氧饱和度、贫血、体能测量和其他可能适合干预的因素的关系。归根结底，我们的目标是找到延长非老年和百岁老人无残疾寿命的方法。如果低氧饱和度、贫血或身体表现不佳与超长寿命中患痴呆症或残疾的风险增加有关，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防止或延缓高龄老年人认知和日常生活能力的丧失。对我们人口中增长最快的那部分人来说，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的认知和功能状态的因素是这项提案的主要目标。在我们对最年长老人的痴呆症、残疾和虚弱的前瞻性研究中，我们将调查与痴呆症、残疾和动脉血氧饱和度、贫血、体能测量和其他可能适合干预的因素的关系。归根结底，我们的目标是找到延长非老年和百岁老人无残疾寿命的方法。如果低氧饱和度、贫血或身体表现不佳与超长寿命中患痴呆症或残疾的风险增加有关，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防止或延缓高龄老人认知和日常生活能力的丧失。对我们人口中增长最快的那部分人来说，潜在的公共卫生影响是巨大的。