Clinical and Pathological Studies in the Oldest Old

最古老的临床和病理学研究

• 批准号: 6934497
• 负责人: CLAUDIA H. KAWAS
• 金额: $ 119.18万
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934497
• 关键词: aging; antioxidants; brain; clinical research; cognition; dementia; disease /disorder prevention /control; disease /disorder proneness /risk; epidemiology; functional ability; gene environment interaction; human mortality; human subject; human very old age (85+); inflammation; longevity; longitudinal human study; mental health epidemiology; neuropathology; nonsteroidal antiinflammatory agent; oxidative stress; postmortem; psychological aspect of aging; questionnaires

DESCRIPTION (provided by applicant): In the next two decades, the number of Americans aged 90 years and older will nearly double to over 3 million people. Because previous studies have few, if any, subjects over 90 years of age, little is known about these pioneers or about factors associated with successful aging and health in this group. The goals of this application are to investigate clinical, genetic, and pathological factors associated with extreme old age. We superimpose our investigations on the Leisure World Cohort Study, initiated in 1981. For over 20 years, cohort members (N=13,979) have provided medical history and lifestyle information including morbid conditions, family history, exercise, social activities, and medication use such as antioxidants and non-steroidal anti-inflammatory drugs(NSAIDS). Our central hypothesis is that oxidative damage and inflammation in the brain results in aging, disease and death and that intake of antioxidants and NSAIDS will slow cognitive decline and improve the health of the oldest old. Our Specific Aims are: (1) to examine factors associated with longevity in the 4,682 cohort members who reached age 90 compared to the 6734 who did not, (2) to determine the prevalence, incidence, and risk factors for dementia in 1,644 living cohort members in their tenth and eleventh decades, (3) to conduct longitudinal follow-up to measure rates of cognitive and functional decline in these oldest old subjects, and (4) to complete our investigations with clinical pathological correlates of brain aging in health and disease, focusing on the association of cerebral measures of oxidative injury, inflammatory markers, and plaque and tangle pathology as it relates to clinical status and previous use of antioxidant and anti-inflammatory compounds. The Leisure World Cohort Study provides a unique population sample for the study of genetic and environmental factors associated with longevity and successful aging in the oldest old. With a substantial cohort of committed subjects and 20 years of prospective data, our proposed investigations can contribute much to the understanding of cognition, functional abilities, and cerebral pathology in the oldest members of our society.

描述（由申请人提供）：在未来二十年中，90 岁及以上的美国人数量将几乎翻倍，达到 300 万人以上。由于之前的研究很少（如果有的话）年龄超过 90 岁的受试者，因此对这些先驱者或与该群体成功老龄化和健康相关的因素知之甚少。 该应用的目标是调查与高龄相关的临床、遗传和病理因素。我们将我们的调查与 1981 年启动的休闲世界队列研究相结合。20 多年来，队列成员 (N=13,979) 提供了病史和生活方式信息，包括疾病状况、家族史、锻炼、社交活动和药物使用情况，例如作为抗氧化剂和非甾体抗炎药（NSAIDS）。 我们的中心假设是，大脑中的氧化损伤和炎症会导致衰老、疾病和死亡，而摄入抗氧化剂和非甾体抗炎药将减缓认知能力下降并改善老年人的健康。 我们的具体目标是：(1) 检查 4,682 名年满 90 岁的队列成员与 6734 名未年满 90 岁的队列成员的长寿相关因素，(2) 确定 1,644 名活着的队列中痴呆症的患病率、发病率和危险因素成员在十岁和十一岁的时候，（3）进行纵向随访，以测量这些最年长的老年受试者的认知和功能下降率，以及（4）完成我们的临床调查健康和疾病中大脑衰老的病理相关性，重点关注氧化损伤、炎症标记物以及斑块和缠结病理学的大脑测量的关联，因为它与临床状态和先前使用的抗氧化剂和抗炎化合物有关。 休闲世界队列研究为研究与老年人的长寿和成功老龄化相关的遗传和环境因素提供了独特的人群样本。凭借大量坚定的受试者群体和 20 年的前瞻性数据，我们提出的研究可以为了解我们社会最年长成员的认知、功能能力和脑病理学做出很大贡献。