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

专利授权摘要 尽管美国人的预期寿命稳步增长，许多人活到90岁或更高， 大多数人的健康和生活质量极差。虽然阿尔茨海默病和相关痴呆症（ADRD） 影响15%的65岁以上的人，到90岁以上，这个数字增加到惊人的40- 50%。最年长的人 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，关于流行病学的信息非常缺乏， 最年长者的轻度认知障碍（MCI）和ADRD，特别是在非白人和来自较低年龄段的人中， 社会经济阶层。这是一个很大的问题，因为非白人少数民族的比例正在迅速增加。 到2060年将占最年长者的36%。痴呆症和MCI的发病率在以下人群之间差异很大： 族裔群体在较年轻的年龄，但完全不知道的模式是否是相同的最年长的老人。大脑 到目前为止，在最年长的老年人中进行的成像和神经病理学研究表明，血管病变而不是AD， 在痴呆症中起着更大的作用，但这还没有在非白人中进行过研究。除了缺乏人口统计学 在90多项针对高龄老人的研究中，缺乏关于早期和中年风险以及保护措施的信息。 老年期ADRD和脑病理学因素。对最年长者的生命历程研究势在必行;然而， 由于需要进行涵盖数十年的研究，因此成本高且在后勤方面具有挑战性。因此，小心 在这一高危人群中，迫切需要对生命周期健康和保护机制进行调查， 梳理出哪些因素，在什么时间点，可以保护一个人。我们提出了一个前所未有的 对30-50岁高龄老年人MCI和痴呆的流行病学研究 收集生活史和健康数据。Kaiser Permanente拥有无与伦比的近7121名员工 目前年龄在90岁以上（36%非白人），参与多相健康研究（MHC），基线 从1964年到1973年的检查，以及1991年的随访。这些数据，加上精细的电子医疗记录， 从1996年至今提供了一个特殊的和全面的资源。800名MHC成员年龄 90+（600名非白色和200名白色）无痴呆症的患者将入组痴呆症和MCI的研究。 将对200名个体（150名非白色）的随机子样本进行结构MRI和淀粉样蛋白PET检查 和50白色）以表征脑淀粉样蛋白负荷、血管病变和萎缩。捐赠大脑给 将对所有800名参与者进行尸检病理学检查。我们的总体目标是估计发病率 在一个不同年龄组的老年痴呆症/MCI，确定中年和晚年的风险和保护因素， 了解这个多样化的最年长人群的大脑和大脑病理模式。

ABSTRACT OF PARENT GRANT 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, 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 oldest-old, 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 oldest-old. Dementia and MCI rates highly vary between ethnic groups at younger ages yet it is completely unknown if patterns are the same in the oldest-old. Brain imaging and neuropathology studies so far in oldest-old 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 oldest-old, there is a paucity of information on early and midlife risk and protective factors for ADRD and brain pathology in oldest-old. Lifecourse studies in the oldest-old 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 oldest-old 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+ (600 Non-White 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 (150 Non White and 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 oldest-old, identify midlife and late-life risk and protective factors, and understand the pattern of cerebral and brain pathologies in this diverse oldest-old population.