Trajectories of Cognition in Middle Age: Implications for Alzheimer's Disease and Related Dementias in the U.S.

项目总结/摘要 美国阿尔茨海默病和相关痴呆症（ADRD）患者人数预计将达到13.8 到2050年，亿。鉴于目前缺乏ADRD的疾病改善治疗方法， ADRD发展了几十年，人们对制定预防策略的兴趣越来越大。中年（即， 45-64岁）越来越多地被认为是一个关键的生命过程时期，以针对认知障碍的可改变的风险因素。 下降和ADRD。先前的研究已经确定了中年的个人水平的风险因素，包括慢性 高血压和肥胖等疾病以及过度饮酒等健康相关行为。的 2020年柳叶刀委员会估计，解决这些中年风险因素可能导致高达15%的 预防或延缓痴呆症。然而，最近的数据表明，需要超越个人- 水平因素，以检查环境暴露对改善中年健康结果的潜在作用 并减轻痴呆症的总体负担。自1990年以来，作为艾滋病毒/艾滋病风险因素的慢性病的流行率 ADRD在中年人中有所增加，特别是在社会经济地位较低的人中。 造成这些趋势的原因尚不完全清楚，但一个主要的假设是， 年龄是导致过早发病的老化有关的条件，通过暴露在社会和身体 环境（例如，社会支助水平、犯罪、粮食不安全、污染）。越来越多的研究 将这些环境因素与老年人认知能力下降和ADRD的风险联系起来，这些因素可能 也会影响中年人的认知轨迹和ADRD风险。然而，关键的知识差距 保持。首先，目前尚不清楚中年人的认知结果是否正在恶化，也不清楚环境因素是否正在恶化。 暴露于辐射会增加中年认知能力下降的风险。此外，尽管认知能力下降， 老年人的ADRD是环境和遗传风险因素相互作用的结果，目前尚不清楚如何影响ADRD。 遗传风险导致中年认知能力下降。一项针对中年人的纵向研究， 包括对环境暴露的测量，需要遗传数据来解决这些问题。的 该项目的目的是研究中年人的认知结果是否会恶化，以及如何恶化。 环境和遗传风险因素导致这一年龄组的认知能力下降。具体目标是 目的：（1）研究美国中年人认知障碍的流行病学，包括查明 随着时间的推移，认知轨迹和“无痴呆的认知障碍”（CIND）的发生率;（2）确定 环境和遗传因素预测认知轨迹和事件CIND;（3）复制我们的 在第二个数据集中进行分析。我们将使用具有全国代表性的纵向数据来完成这些目标 健康与退休研究的报告。研究结果将有助于阐明 研究人员发现，老年痴呆症患者的认知能力下降，并为政策规划提供信息，以减轻预计的痴呆症负担。

PROJECT SUMMARY/ABSTRACT The number of Americans with Alzheimer's disease and related dementias (ADRD) is projected to reach 13.8 million by 2050. Given the current lack of disease-modifying treatments for ADRD coupled with evidence that ADRD develops over decades, there is growing interest in developing prevention strategies. Middle age (i.e., 45-64 years) is increasingly recognized as a key life course period to target modifiable risk factors for cognitive decline and ADRD. Prior studies have identified individual-level risk factors in middle age, including chronic conditions such as hypertension and obesity and health-related behaviors such as excessive alcohol use. The 2020 Lancet Commission estimated that addressing these mid-life risk factors could result in up to 15% of dementias being prevented or delayed. However, recent data suggests the need to look beyond individual- level factors to examine the potential role of environmental exposures to improve health outcomes in mid-life and reduce overall dementia burden. Since 1990, the prevalence of chronic conditions that are risk factors for ADRD has increased in middle-aged adults, particularly in individuals with lower socioeconomic status (SES). The reasons for these trends are not yet fully understood, but a leading hypothesis is that lower SES in middle age is leading to premature onset of aging-related conditions through exposures in the social and physical environment (e.g., levels of social support, crime, food insecurity, pollution). A growing number of studies have linked such environmental factors to risk of cognitive decline and ADRD in older adults, and these factors could also be impacting cognitive trajectories and risk of ADRD in middle age. However, key knowledge gaps remain. First, it is unknown if cognitive outcomes are worsening in middle-aged adults, nor if environmental exposures increase the risk of cognitive decline in middle age. Additionally, whereas cognitive decline and ADRD in older adults result from the interplay of environmental and genetic risk factors, it is unclear how genetic risk contributes to cognitive decline in middle age. A longitudinal study of middle-aged adults that includes measures of environmental exposures and genetic data is needed to address these questions. The objective of the proposed project is to examine if cognitive outcomes are worsening in middle age and how environmental and genetic risk factors contribute to cognitive decline in this age group. The specific aims are to: (1) examine the epidemiology of cognitive impairment in middle-aged adults in the U.S., including identifying cognitive trajectories and incidence of “cognitive impairment no dementia” (CIND) over time; (2) determine if environmental and genetic factors predict cognitive trajectories and incident CIND; and (3) replicate our analyses in a second dataset. We will complete these aims using longitudinal nationally representative data from the NIA-funded Health and Retirement Study. Findings will help elucidate the burden and mechanisms of cognitive decline in middle age and inform policy planning to mitigate the projected burden of dementia.