Epidemiology of Age-related Dementia, Mild Cognitive Impairment and Brain Pathology in a Multiethnic Cohort of Oldest-Old

摘要 尽管美国的预期寿命稳步增长，许多人活到90岁或以上，但健康和 对大多数人来说，生活质量极差。而阿尔茨海默病和相关痴呆症(ADRD)影响了15% 在65岁以上的人中，到90岁以上时，这一数字增长到惊人的40%-50%。年龄最大(OO)的人 90岁以上的老年人是美国老年人口中增长最快的部分，目前占4.7%， 预计到2060年将增加到11.5%。然而，关于流行性感冒的流行病学信息非常匮乏。 OO人群中的轻度认知障碍(MCI)和ADRD，特别是在非白人和低收入人群中 社会经济阶层。这是非常有问题的，因为非白人少数民族的比例很快 不断增加，到2060年将占OO的36%。不同种族的痴呆症和MCI发病率差异很大 然而，OO中的模式是否相同还是完全未知的。脑部成像和 到目前为止，OO的神经病理学研究表明，血管病理而不是AD，在 痴呆症，但这还没有在非白人身上进行检查。超越90多年人口多样性的缺乏 OO的研究，缺乏关于ADRD和ADR的早中年风险和保护因素的信息 OO中的脑病理。OO的终身课程研究势在必行；但成本非常高，在后勤方面具有挑战性 因为需要进行长达数十年的研究。因此，仔细调查生命周期健康和 在这个高危人群中，迫切需要保护机制来梳理哪些因素，在什么情况下 时间点，可以保护一个人。我们提出了一项史无前例的MCI流行病学研究。 老年痴呆症患者我们已经前瞻性收集了30-50年的生活史和健康资料。凯撒 Permanente拥有一个无与伦比的队列，目前有近7121名年龄在90岁以上的人(36%是非白人) 参加了1964-1973年的多相健康研究(MHC)，并进行了基线检查，并对 1991年。这些数据，加上1996年至今的细粒度电子病历，提供了一种特殊的 和综合资源。800名90岁以上的MHC成员(300名黑人，300名亚洲人，200名白人) 没有痴呆症的人将参加一项关于痴呆症和MCI的研究。结构核磁共振和淀粉样蛋白PET将是 从200名个体(75名黑人，75名亚洲人，50名白人)的随机子样本中获得，以表征大脑 淀粉样蛋白负荷、血管损伤和萎缩。将寻求脑部捐献以用于尸检 所有800名参与者。我们的总体目标是评估不同人群中痴呆/MCI的发病率。 OO，识别中老年风险和保护因素，了解大脑和大脑的模式 在这个不同的OO人群中的病理。

Abstract Though life expectancy in the US has steadily increased and many people live to age 90 and beyond, health and quality of life is extremely poor for most. While Alzheimer's disease and related dementias (ADRD) affect 15% of those age 65+, by age 90+, this number increases to a startling 40-50%. The oldest-old (OO), people aged 90+, are the fastest growing segment of the elderly population in the US, currently comprising 4.7% and expected to increase to 11.5% by 2060. Yet there's an enormous dearth of information on the epidemiology of mild cognitive impairment (MCI) and ADRD in the OO, particularly in non-whites and those from lower socioeconomic classes. This is highly problematic as the proportion of non-white minorities is rapidly increasing and by 2060 will represent 36% of the OO. Dementia and MCI rates highly vary between ethnic groups at younger ages yet it is completely unknown if patterns are the same in the OO. Brain imaging and neuropathology studies so far in OO suggest that vascular pathologies, rather than AD, play a larger role in dementia, yet this hasn't been examined in non-Whites. Beyond the lack of demographic diversity in 90+ studies of OO, there is a paucity of information on early and midlife risk and protective factors for ADRD and brain pathology in OO. Lifecourse studies in the OO are imperative; yet very costly and logistically challenging since studies encompassing multiple decades are needed. Thus, careful investigation of lifecourse health and protective mechanisms is strongly needed in this high risk population to tease apart which factors, at what point in time, may protect an individual. We propose an unprecedented epidemiologic study of MCI and Dementia in the OO whom we have 30-50 years of prospectively collected life history and health data. Kaiser Permanente has an unparalleled cohort of almost 7121 individuals currently aged 90+ (36% Non-White) who participated in the Multiphasic Health Study (MHC) with baseline exams from 1964-1973, and follow-ups to 1991. These data, joined with granular electronic medical records from 1996–present provide an exceptional and comprehensive resource. Eight hundred MHC members aged 90+ (300 Black, 300 Asian, and 200 White) without dementia will enroll in a study of incident dementia and MCI. Structural MRI and Amyloid PET will be obtained on a random subsample of 200 individuals (75 Black, 75 Asian, 50 White) to characterize cerebral amyloid burden, vascular lesions, and atrophy. Brain donation for postmortem pathology will be sought from all 800 participants. Our overall objectives are to estimate incidence of dementia/MCI in a diverse cohort of OO, identify midlife and late-life risk and protective factors, and understand the pattern of cerebral and brain pathologies in this diverse OO population.