Clinical and Pathological Studies in the Oldest Old

最古老的临床和病理学研究

基本信息

批准号：
8230622
负责人：
CLAUDIA H. KAWAS
金额：
$ 136.92万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
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/8230622
关键词：
Activities of Daily Living Age Aged, 80 and over Aging Alzheimer&apos s Disease Amyloid Amyloid beta-Protein Anemia Anterior Autopsy Biological Blood Vessels California Centenarian Clinical Clinical Data Cognition Cognitive Cognitive deficits 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 Pathway interactions Pennsylvania Performance Population Prefrontal Cortex Principal Investigator Prospective Studies Public Health Research Research Personnel Resources Risk Risk Factors Role Sampling Scientist Societies Speed 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 population based prevent programs prospective research study sex synuclein tau Proteins tau-1

项目摘要

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.

描述（由申请人提供）：2003年启动的项目摘要是90+研究的目标是在90岁及以上的人群样本中进行前瞻性临床，病理和遗传研究。 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).我们的研究强调了该年龄段的痴呆症和残疾的危险因素，强调可能改变的因素（氧饱和，贫血和身体性能），并有可能为最古老的老年人的未来干预研究提供基础。基于我们的初步研究，我们假设较差的动脉氧饱和度是认知能力下降和痴呆症的危险因素，而贫血和身体表现措施（例如步行速度和手夹）是残疾，脆弱性和非痴呆症患者功能下降的危险因素。该年龄范围内所有痴呆受试者的一半没有具有明显的经典AD或其他病理来解释认知损失。在此应用中，新的合作增强了我们研究最古老的旧旧的认知生物学相关性的临床病理研究（AIM 4）。加利福尼亚大学，欧文分校，宾夕法尼亚大学和约翰·霍普金斯医学院的研究人员将研究来自我们良好特征学科的脑组织，当我们测试我们的假设，这些假设可溶于A2，TAU和1的syn依者，而不是不溶的，不溶于A2，Synuclein的寡聚物种，可能是对90岁以上的人（与90岁以上的人）相关的人（目标）4B（AIM）4B（AIM）（目标）4B（AIM）4B（AIM）4B）神经元的完整性和回路可能会通过其他与年龄相关的机制导致认知损失（AIM 4C）。最后，我们将开发我们的临床数据和生物样品（脑组织和DNA），作为可以与全球科学家积极共享的资源。影响我们社会中最高级成员的认知和功能状况的项目叙事理解因素是该提议的主要目标。在最古老的痴呆症，残疾和脆弱性的前瞻性研究中，我们将研究与痴呆症，残疾和脆弱的动脉O2饱和度，贫血，身体表现措施以及其他可能适合干预的因素的关系。最终，我们的目标是找到延长无残障人士生活的方法。如果较低的O2饱和度，贫血或身体不良与异常长寿命中痴呆或残疾的风险增加有关，则将为实验研究提供基础，以确定氧气治疗，贫血或运动是否可以防止或延迟在老年历史中丧失或延迟日常生活的认知和活动。潜在的公共卫生影响对于我们人口中增长最快的部分是巨大的。