Clinical and Pathological Studies in the Oldest Old

高龄老人的临床与病理研究 在接下来的20年里，美国90岁及以上的老年人数量将翻一番，达到300多万人。 因为以前的研究很少有，如果有的话，超过90岁的受试者，对这些先驱者或对他们的研究知之甚少。 与成功老龄化和健康相关的因素。 这项计划的目的是调查与极端老年相关的临床，遗传和病理因素。 我们回顾了1981年发起的休闲世界队列研究的调查。20多年来， 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、 病史、运动、社会活动和药物使用，如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导致衰老、疾病和死亡， 摄入抗氧化剂和非甾体类抗炎药将减缓认知能力的下降，改善老年人的健康。 我们的具体目标是：（1）在4，682名达到年龄的队列成员中检查与长寿相关的因素 90人与6734人相比，（2）确定1，644人中痴呆的患病率，发病率和危险因素 生活在他们的第十和第十一个十年的队列成员，（3）进行纵向随访，以衡量率 认知和功能下降，这些最古老的老年人，（4）完成我们的调查与临床 健康和疾病中脑老化的病理相关性，重点是脑功能指标的相关性， 氧化损伤、炎症标志物、斑块和缠结病理学，因为它与临床状态和既往使用有关 of antioxidant抗氧化剂and anti-inflammatory抗炎compounds化合物. 休闲世界队列研究为遗传和环境的研究提供了一个独特的人口样本 与长寿和高龄老人成功老龄化相关的因素。有一大批致力于 受试者和20年的前瞻性数据，我们提出的调查可以大大有助于了解 认知，功能能力和大脑病理学在我们社会中最古老的成员。

CLINICAL ANDPATHOLOGICAL STUDIES IN THE OLDEST OLD In the next two decades, the numberof 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 proposal 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-inflammatorydrugs (NSAIDS). Our central hypothesis is that oxidative damage and inflammationin the brain results in aging, disease and death and that intake of antioxidants and NSAIDS will slow cognitive decline and improvethe 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, inflammatorymarkers, and plaqueand tangle pathology as it relates to clinical status and previous use of antioxidant and anti-inflammatorycompounds. 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.