Cognitively Healthy Nonagenarians in the Cross Cohort Collaboration (CCC)

跨队列合作 (CCC) 中认知健康的九十多岁老人

• 批准号: 9546246
• 负责人: Sudha Seshadri
• 金额: $ 611.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9546246
• 关键词: Affect; Age; Aged, 80 and over; Aging; Albumins; Alzheimer' s Disease; Anisotropy; Argyrophilic Grain Disease; Atherosclerosis Risk in Communities; Atrophic; Autopsy; Biology; Blood Vessels; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Cardiac; Caring; Cities; Clinical; Cognition; Cognitive; Cohort Studies; Collaborations; Country; Coupled; Data; Dementia; Diet; Disease; Elderly; Endocrine system; Enrollment; Etiology; Framingham Heart Study; Functional disorder; Funding; Genes; Grant; Health; Hepatic; Hippocampus (Brain); Hypertension; Immune; Incidence; Income; Individual; Infarction; Inflammatory; Injury; Kidney; Learning; Left Ventricular Ejection Fraction; Life; Life Expectancy; Life Style; Logistic Models; Longitudinal cohort study; Lung; Magnetic Resonance Imaging; Marital Status; Measures; Meta-Analysis; Metabolic; Modeling; Neurologic; Neurology; Nonagenarian; Organ; Outcome; Participant; Pathology; Pattern; Persons; Phenotype; Physical activity; Population; Population Study; Prevalence; Prevention; Probability; Prospective cohort; Protocols documentation; Public Health; Publications; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Pulse Pressure; Risk; Risk Factors; Sample Size; Savings; Sleep; Social Network; Statistical Models; Stroke; Stroke prevention; Survivors; Susceptibility Gene; Thick; Time; age group; aged; aging brain; baby boomer; body system; bone; cardiovascular health; cerebral atrophy; cognitive testing; cohort; cost; follow-up; genomic data; healthy aging; high risk; lifestyle factors; middle age; non-genetic; novel; population based; protective factors; social; white matter; working group

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.

项目概要 面临痴呆症风险和罹患痴呆症的人口增长最快的是年龄最大的老年人，即 80 岁以上的人 到 2030 年，二分之一的阿尔茨海默痴呆症 (AD) 病例可能会发生在这个年龄段。 基础生物学以及血管和生活方式危险因素对痴呆风险的影响似乎是 此外，这些因素可能会相互作用，产生影响。 当个体进入老年时，通过大脑状态（MRI）反映的早期和中年风险暴露 （年龄65±5岁），并伴有随着年龄增长而出现的多种全身性疾病。 对同一个人的纵向有限数据，从 60 多岁到 80 多岁，跟踪了 10-25 年， 我们建议在 8 项大型人群研究中开展跨队列合作 (CCC)（弗雷明汉研究）。 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)、三城市研究 (3C)、鹿特丹研究 (RS)、社区动脉粥样硬化风险 研究 (ARIC)、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 年至 2001 年间获得了脑部 MRI 和认知评估，并继续跟踪 参与者，共有超过 15,000 名参与者接受了初始脑部 MRI 和认知检查 评估是在 70 岁之前以及随后的认知、痴呆状态和/或 MRI 进行的 获得评估直至他们死亡、患上痴呆症或年满 80 岁且无任何症状 这些参与者还对血管、代谢和生活方式进行了详细、反复的评估。 60 岁及以后以及 80 岁以后的危险因素、中风和其他器官系统的健康。 最后，超过 27,000 名参与者拥有 80 岁以上的认知数据（使用 MRI 的数据超过 5000 名）来研究近似的认知数据。 我们提出以下目标： 目标 1： 关联各种测量指标，例如已建立的和新型的脑损伤 MRI 标记（梗死、WMH、 微出血、海马体积、皮质萎缩模式、微梗塞、血管周围空间扩大等） 其他器官系统的功能障碍或疾病，以及血管、代谢、社会和生活方式的测量，收集 60-70 岁时活到 85 (+/- 5) 岁且无痴呆的可能性。 目标 1 中检查的相同 MRI、器官功能和危险因素，记录于 60-70 岁和 70-80 岁 80 岁后患临床痴呆的概率。目标 3：检查是否、如何以及程度如何 全身器官功能障碍和 60 岁以上的危险因素改变了脑损伤之间的关联 目标 4：老年人认知健康老龄化与临床痴呆的标志物和概率。 检查关键的 AD 相关基因（例如 APOE、BDNF、BIN1）是否会改变目标 1 和 2 中看到的关联， 或目标 3 中探讨的相互作用。我们的研究结果将有助于更有效、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。