Clinical, Imaging, and Pathological Studies in the Oldest Old: The 90+ Study

项目摘要 这项90岁以上的研究于2003年1月1日开始，是一项以人口为基础的样本，对象是休闲娱乐活动中最年长的幸存者。 世界队列研究（LWCS，1981 - 1984年入组）。超过1，800名参与者，90+研究是其中之一， 世界上规模最大、时间最长的老年痴呆症、认知能力下降、残疾和虚弱的研究。以上的人 90岁是人口中增长最快的部分，对公共卫生的影响最大，因为痴呆症的风险是 在这些人中异常高，在百岁老人中达到惊人的40%。然而，许多年龄最大的老人 保持上级的认知表现，直到他们的第十个十年及以后（认知弹性），通常在 存在神经病理学变化（存在病理学的认知恢复力）。生活方式，共病 条件、遗传和其他因素与这种认知弹性有关，但尚未得到充分研究。在 这个应用程序，我们扩展我们的研究，以调查这些显着的个人认知弹性。目标1： 考虑早期（在LWCS中提前30岁）和晚期（90岁以上）的生活方式以及与认知功能相关的其他因素。 resilience.研究了在病理情况下与保持上级认知能力相关的因素 目标2在我们的成像研究中，利用我们90岁以上的大型队列，我们前瞻性地随访了 无痴呆的个体，以估计与MRI和PET相关的痴呆发病率和认知下降率 目标3中的生物标志物。我们分析了低水平的多种神经病理学改变在表达中的作用， 目标4中的痴呆症。最后，通过这项申请，我们将招募最后一位有资格参加我们研究的LWCS参与者， 并完全确定所有先前在90+研究中确定的结果（痴呆，CIND，MCI，虚弱， 残疾和死亡）。我们将使这个跨越近四十年的数据集可用于研究 目标5（Aim 5） 凭借我们广泛的数据库，独特的大型群体特征良好的个人，广泛和 多学科纵向随访，创新的神经病理学和神经影像学研究，我们是 非常适合做老年痴呆症和恢复力的研究。识别与认知相关的因素 恢复力和痴呆症，包括可改变的生活方式因素和成像生物标志物，将有助于我们 了解健康和疾病中的老龄化，并为促进成功老龄化的干预措施提供潜在目标。

Project Summary The 90+ Study was initiated January 1, 2003 as a population-based sample of oldest-old survivors of the Leisure World Cohort Study (LWCS, enrollment 1981-1984). With more than 1,800 participants, The 90+ Study is one of the largest and longest studies in the world of dementia, cognitive decline, disability, and frailty in the oldest-old. People over 90 are the fastest segment of the population and have the greatest public health impact as the risk of dementia is extraordinarily high in these individuals, reaching a staggering 40% per year in centenarians. However, many oldest old maintain superior cognitive performance well into their tenth decade and beyond (cognitive resilience), often in the presence of neuropathological changes (cognitive resilience in the presence of pathology). Lifestyle, co-morbid conditions, genetics, and other factors have been implicated in this cognitive resilience, but have not been well studied. In this application, we extend our studies to investigate cognitive resilience in these remarkable individuals. In Aim 1, we consider early (30 years earlier in the LWCS) and late (at age 90+) lifestyle and other factors in relation to cognitive resilience. Factors related to the maintenance of superior cognitive abilities in the presence of pathology are investigated in Aim 2. Taking advantage of our large cohort of 90+ year-olds in our imaging studies, we prospectively follow individuals without dementia to estimate incidence of dementia and rates of cognitive decline in relation to MRI and PET biomarkers in Aim 3. We analyze the role of low levels of multiple neuropathologic changes in the expression of dementia in Aim 4. Finally, with this application, we will recruit the last living LWCS participants eligible for our study, and complete ascertainment of all previously established outcomes in The 90+ Study (dementia, CIND, MCI, frailty, disability, and mortality). We will make this dataset spanning almost four decades publically available to the research community (Aim5). With our extensive database, unique large cohort of well-characterized individuals, extensive and multidisciplinary longitudinal follow-up, and innovative neuropathological and neuroimaging investigations, we are ideally positioned to do studies of dementia and resilience in the oldest-old. Identifying factors related to cognitive resilience and dementia, including modifiable lifestyle factors and imaging biomarkers, would contribute to our understanding of aging in health and disease and provide potential targets for interventions to promote successful aging.