Clinical and Pathological Studies in the Oldest Old

描述(申请人提供)：在接下来的20年里，90岁及以上的美国人的数量将增加近一倍，达到300多万人。由于之前的研究几乎没有90岁以上的受试者，因此对这些先驱或这一群体中与成功老龄化和健康相关的因素知之甚少。 这个应用程序的目标是调查与极端老年相关的临床、遗传和病理因素。我们将我们的调查与始于1981年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，包括疾病情况、家族史、锻炼、社交活动和药物使用，如抗氧化剂和非类固醇抗炎药(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，而抗氧化剂和非类固醇类药物的摄入将减缓认知衰退，并改善最年长老年人的健康。 我们的具体目标是：(1)在4,682名年满90岁的队列成员中检查与长寿相关的因素，与未达到90岁的6734名成员相比，(2)确定1,644名10岁和11岁的在世队列成员中痴呆症的患病率、发病率和危险因素，(3)进行纵向随访，测量这些年龄最大的受试者的认知和功能衰退率，以及(4)完成与健康和疾病中脑老化的临床病理相关的调查，重点关注大脑氧化损伤、炎症标记物、以及斑块和纠缠病理，因为它与临床状态和以前使用过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高龄老年人长寿和成功老龄化相关的遗传和环境因素提供了一个独特的人口样本。有了大量承诺的受试者和20年的前瞻性数据，我们拟议的调查可以为我们社会中年龄最大的成员对认知、功能能力和脑病理的理解做出很大贡献。

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.