Cognitively Healthy Nonagenarians in the Cross Cohort Collaboration (CCC)

项目摘要 患痴呆症风险和罹患痴呆症的人口增长最快的是80岁以上的高龄老人。 或者90年。到2030年，每2例阿尔茨海默病(AD)病例中就有1例可能发生在这个年龄段。这个 基础生物学和血管和生活方式风险因素对痴呆症风险的影响似乎是 不同之处在于年轻人和最年长的人。此外，这些因素可能相互作用，其影响是 个人进入老年时大脑状态(在MRI上)反映的早中期风险暴露 (65±5岁)，以及随着年龄增长而表现出来的多种全身性疾病。然而，有这样一种情况， 相同个体的有限纵向数据，从60多岁到80多岁跟踪了10-25年 更远一点。我们建议对8项大规模人群研究(Framingham)进行跨队列协作(CCC 心脏研究(FHS)，心血管健康研究(CHS)，年龄，基因/易感性研究-雷克雅未克， (AGES-RS)，三个城市研究(3C)，鹿特丹研究(RS)，社区中的动脉粥样硬化风险 奥地利中风预防研究(ASPS)和波美拉尼亚健康研究(SHIP)。 这些研究在1990-2001年间进行了脑部核磁共振检查和认知评估，目前仍在继续。 参与者，总共有超过15,000名参与者，在这些参与者中，初始的脑MRI和认知 评估是在70岁之前以及随后的认知、痴呆症状态和/或MRI获得的 进行评估，直到他们死亡、患上痴呆症或达到80岁以上。 痴呆症。这些参与者还对血管、新陈代谢和生活方式进行了详细、重复的评估 60岁及以上和80岁以后的危险因素、中风和其他器官系统的健康状况。 最后，超过27,000名参与者有超过80岁的认知数据(&gt；5000通过核磁共振)来研究近端 以及老年痴呆和阿尔茨海默病事件的远程决定因素。我们提出以下目标：目标1： 联系各种措施，如已建立的和新的脑损伤的MRI标志物(脑梗塞，WMH， 微出血、海马体体积、皮质萎缩、微梗塞、血管周围间隙扩大等。) 收集其他器官系统的功能障碍或疾病，以及血管、代谢、社会和生活方式指标 在60-70岁时，有可能达到85岁(+/-5岁)，并且没有痴呆。目标2(a-c)：将 目标1中检查的相同MRI、器官功能和风险因素，记录在60-70岁和70-80岁至 80岁后发展为临床痴呆的概率。目标3：检查是否、如何以及达到何种程度 全身性器官功能障碍和60岁以上的危险因素改变了脑损伤之间的联系 高龄老人认知健康老龄化与临床痴呆的标记物和概率。目标4：实现 检查关键的AD相关基因(如APOE、BDNF、BIN1)是否修改AIMS 1和2中的关联， 或AIM 3中探讨的相互作用。我们的发现将有助于更有效、更有针对性地预防 老年痴呆症是任何减少AD负担和成本的公共卫生战略的关键组成部分。

Project Summary The fastest growing demographic at risk of, and suffering from dementia, is the oldest-old, persons over age 80 or 90 years. By 2030, 1 in 2 incident cases of Alzheimer dementia (AD) will likely occur in this age group. The underlying biology and the impact of vascular and lifestyle risk factors on risk of dementia appear to be different in the young-old and oldest-old. Further, these factors likely interact with each other, with the impact of early and midlife risk exposure as reflected by the state of the brain (on MRI) when individuals enter old age (age 65±5 years), and with the multiple systemic illnesses that also manifest with aging. There is however, limited longitudinal data on the same individuals, followed for over 10-25 years from their 60s to their 80s and beyond. We propose a Cross-Cohort collaboration (CCC) across 8 large population studies (the Framingham Heart Study (FHS), The Cardiovascular Health Study (CHS), the Age, Genes/ Susceptibility study- Reykjavik, (AGES-RS), the Three Cities study (3C), the Rotterdam Study (RS), the Atherosclerosis Risk in Communities study (ARIC), the Austrian Study of Stroke Prevention (ASPS) and the Study of Health in Pomerania (SHIP). These studies, which obtained brain MRI and cognitive assessments between 1990-2001, continue to follow participants, and collectively have over 15,000 participants in whom initial brain MRI and cognitive assessments were obtained prior to age 70 and subsequent cognitive, dementia status and/or MRI assessments have been obtained until they died, developed dementia, or reached an age of 80+ free of dementia. These participants also have detailed, repeated assessments of vascular, metabolic and lifestyle risk factors, stroke, and the health of other organ systems at and after age 60 years, and after age 80 yrs. Finally, over 27,000 participants have cognition data beyond age 80 (>5000 with MRI) to study the proximate and remote determinants of incident dementia and AD in the oldest-old. We propose the following aims: Aim 1: To relate various measures such as established and novel MRI markers of brain injury (infarcts, WMH, microbleeds, hippocampal volumes, cortical atrophy patterns, microinfarcts, enlarged perivascular spaces etc.) dysfunction or disease in other organ system, and vascular, metabolic, social and lifestyle measures, gathered at age 60-70 to probability of reaching age 85 (+/- 5) years alive and dementia free. Aim 2 (a-c): To relate the same MRI, organ function and risk factors examined in Aim 1, as recorded at ages 60-70 and 70-80 to probability of developing clinical dementia after age 80. Aim 3: To examine if, how, and to what extent systemic organ dysfunction and risk factors beyond age 60 modified the association between brain injury markers and probabilities of cognitively healthy aging versus clinical dementia in the oldest-old. Aim 4: To examine if key AD related genes (such as APOE, BDNF, BIN1) modify the associations seen in Aims 1 and 2, or the interactions explored in Aim 3. Our findings will facilitate more effective, targeted efforts at prevention of dementia in the oldest-old, a key component of any public health strategy to reduce AD burden and costs.