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

中年认知轨迹：对美国阿尔茨海默病和相关痴呆症的影响

• 批准号: 10301111
• 负责人: Rebecca Tyler Brown
• 金额: $ 47.75万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10301111
• 关键词: Address; Adult; Age; Age of Onset; Aging; Alcohol consumption; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Chronic; Cognition; Cognitive; Coupled; Crime; Data; Data Analyses; Data Set; Dementia; Disease; Elderly; Engineering; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Exposure to; Funding; Genetic; Genetic Risk; Health; Health Status; Health and Retirement Study; Health behavior; Health behavior change; Hypertension; Impaired cognition; Incidence; Individual; Intercept; Intervention; Knowledge; Life Cycle Stages; Link; Longitudinal Studies; Measures; Medical; Neighborhoods; Obesity; Outcome; Participant; Physical environment; Play; Policies; Pollution; Population; Predictive Factor; Prevalence; Prevention; Prevention strategy; Public Health; Risk; Risk Factors; Role; Social Environment; Social support; Study models; Subgroup; Surveys; Testing; Time; United States National Academy of Sciences; age group; base; cognitive impairment no dementia; dementia risk; ethnic minority population; food insecurity; genetic risk factor; high risk; improved; interest; low socioeconomic status; middle age; modifiable risk; novel; premature; prevent; racial and ethnic; trend

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.

项目摘要/摘要 患有阿尔茨海默氏病和相关痴呆症（ADRD）的美国人人数预计将达到13.8 到2050年，百万到2050年。鉴于目前缺乏疾病修改治疗ADRD的治疗方法以及证据表明 ADRD发展了数十年，人们对制定预防策略的兴趣越来越大。中年（即 45 - 64年）越来越被认为是关键的生活课程，以针对认知的可改变风险因素。 衰落和adrd。先前的研究已经确定了中年的个人级别危险因素，包括慢性 高血压和肥胖症以及与健康相关的行为（例如过量饮酒）等疾病。 2020年柳叶刀委员会估计，解决这些中期危险因素可能会导致多达15％ 痴呆症被阻止或延迟。但是，最近的数据表明需要超越个体 - 级别因素，以检查环境暴露的潜在作用，以改善中年的健康状况 并减轻整体痴呆症负担。自1990年以来，慢性病的患病率是危险因素 在中年成年人中，ADRD有所增加，特别是在社会经济地位较低（SES）的个体中。 这些趋势的原因尚未完全理解，但是一个主要的假设是中间的SES较低 年龄通过在社会和身体上的暴露导致与衰老相关的状况过早发作 环境（例如，社会支持水平，犯罪，粮食不安全，污染）。越来越多的研究拥有 将这种环境因素与老年人认知下降和ADRD的风险联系起来，这些因素可能 还会影响中年的认知轨迹和ADRD的风险。但是，关键知识差距 保持。首先，尚不清楚认知结果是否在中年成年人中感到遗憾，也不知道环境 暴露会增加中年认知能力下降的风险。此外，认知能力下降和 老年人的ADRD是由于环境和遗传危险因素的相互作用而导致的，目前尚不清楚如何如何 遗传风险有助于中年认知下降。一项对中年成年人的纵向研究 包括环境暴露的措施和遗传数据以解决这些问题。 拟议项目的目的是检查认知结果是否在中年后悔 环境和遗传危险因素导致该年龄段的认知下降。具体目的是 至：（1）研究美国中年成年人认知障碍的流行病学，包括确定 随着时间的流逝，认知轨迹和“认知障碍无痴呆症”（CIND）的发生率； （2）确定是否 环境和遗传因素可以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。我们将使用纵向全国代表性数据来完成这些目标 来自NIA资助的健康和退休研究。调查结果将有助于阐明燃烧和机制 中年的认知能力下降并为政策计划提供信息，以减轻痴呆症的预计燃烧。