Mechanisms of Risk and Resilience to Age-Related Cognitive Decline: A 60-Year Prospective Prenatal Cohort

与年龄相关的认知衰退的风险和恢复力机制：60 年预期产前队列

基本信息

批准号：
10063316
负责人：
STEPHEN L BUKA
金额：
$ 104.98万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10063316
关键词：
7 year old Address Adolescence Adult Affect Age Age-associated memory impairment Alzheimer&apos s Disease Alzheimer&apos s disease pathology Amyloid beta-42 Amyloid beta-Protein Anatomy Apolipoprotein E Birth Brain Brain Pathology Child Childhood Clinical Cognition Cognitive Cognitive aging Cohort Studies Data Collection Development Economic Burden Economics Education Elderly Equilibrium Etiology Failure Family Functional Magnetic Resonance Imaging Genotype Health Status Healthcare Systems Impaired cognition Incidence Income Individual Individual Differences Investigation Lead Life Life Experience Link Longevity Longitudinal cohort Measures Neurocognitive Neuropsychology Occupational Onset of illness Outcome Participant Pathology Pathway interactions Pattern Perinatal Phase Physical activity Plasma Population Pregnancy Prevention strategy Race Research Risk Saliva Sampling Studies Social Behavior Structure System Therapeutic Time age related childhood adversity cognitive ability cognitive control cognitive function cognitive neuroscience cognitive testing cohort early childhood effective therapy ethnic diversity indexing insight lifestyle factors member middle age neural network neuroimaging novel novel strategies pre-clinical prenatal prevent programs prospective racial and ethnic resilience social

项目摘要

PROJECT SUMMARY/ABSTRACT The failure to find any effective treatment for Alzheimer’s disease (AD) despite over four decades of research underscores the critical need for new strategies to prevent or delay disease onset. The proposed investigation aims to examine mechanisms of risk and resilience to age-related cognitive decline by leveraging recent advances in cognitive neuroscience and a unique 60-year longitudinal prenatal cohort. The concept of reserve has been developed to account for the large individual differences in cognitive aging trajectories, with nascent understanding of potential modifiable determinants of reserve. However, fundamental questions remain regarding, for instance, the impact of education, cognitively stimulating activities in adulthood, or early childhood enrichment on reserve mechanisms and cognitive decline. Previous investigations have been hampered by a number of limitations, including the lack of: 1) prospective measures of early childhood cognition, needed to address critical issues of reverse causation plaguing this field; 2) indices of adult cognitive decline over a large time window; 3) measures of relevant sociobehavioral factors across the entire lifespan; and 4) economic and racial/ethnic diversity of study samples. This proposal addresses these limitations by extending our continued study of the Providence RI cohort of the US Collaborative Perinatal Project (CPP). The original CPP involved systematic data collection from pregnancy through age 7 years, including measures of three key early life factors thought to influence cognitive trajectories in later life: early childhood IQ, family SES, and childhood adversity. We conducted a comprehensive cognitive assessment of 720 members of this cohort at age 35. We propose to reassess these participants (now approaching age 60) with a detailed neuropsychological battery to examine cognitive decline over a 25-year period. We will also assess engagement in cognitively stimulating activities, physical activity, occupational complexity, income, and health status. Participants will provide biosamples for plasma beta-amyloid (Aβ) 42/40 ratio and apolipoprotein E (APOE) genotype, and will undergo structural and functional MRI, providing operationally-defined brain measures of reserve. Finally, we propose a novel conceptual framework linking lifespan factors to cognitive outcomes through distinct brain mechanisms. This framework drives our aims which are: (1) Determine the relative influence of educational attainment, early life, and adult lifestyle factors on cognitive level and decline in late middle-aged adults; (2) Determine the relative contributions of specific brain reserve mechanisms to cognitive decline; and (3) Identify major determinants of brain reserve mechanisms in later life. A projected doubling of the elderly population by 2050 will place tremendous AD-related burden on the U.S. healthcare system. By providing novel insights into mechanisms of risk and resilience, findings may lead to new strategies to significantly reduce this burden by delaying cognitive decline and the onset of Alzheimer’s Disease.

项目摘要/摘要在四十年的研究强调了对预防或延迟疾病发作的新策略的关键需求。提议调查旨在检查风险和韧性机制，从而对年龄相关的认知能力下降利用最新的认知神经科学和独特的60年纵向产前队列的进步。储备的概念已经开发出来，以说明认知衰老的巨大个体差异轨迹，对潜在可修改的储备决定剂的新生理解。然而，关于教育的影响，认知刺激的影响仍然存在基本问题成年或幼儿期在储备机制和认知能力下降上的活动。先前的调查受到许多局限性的阻碍，包括缺乏：1）幼儿认知的前瞻性措施，需要解决反向发生的关键问题困扰这个领域； 2）在较大的时间窗口内成人认知下降的指标； 3）相关的度量整个生命周期中的社会行为因素； 4）研究的经济和种族/种族多样性样品。该提案通过扩展我们对普罗维登斯RI的持续研究来解决这些局限性美国协作围产期项目（CPP）的队列。原始CPP涉及系统数据收集从怀孕到7岁，包括三个关键的早期生命因素的措施后来的认知轨迹：幼儿智商，家庭SES和童年广告。我们进行了一个对35岁的该队列的720名成员的全面认知评估。我们建议放松这些参与者（现已接近60岁），带有详细的神经心理电池来检查在25年期间的认知能力下降。我们还将评估参与认知刺激活动，体育活动，职业复杂性，收入和健康状况。参与者将提供生物样本对于血浆β-淀粉样蛋白（Aβ）42/40的比例和载脂蛋白E（APOE）基因型，将经历结构性和功能性MRI，可提供操作定义的大脑储备指标。最后，我们提出了一本小说通过不同的大脑机制将寿命因素与认知结果联系起来的概念框架。该框架推动了我们的目标：（1）确定教育程度的相对影响，早期生活以及后期成年人认知水平和下降的成人生活方式因素；（2）确定特定的大脑储备机制对认知能力下降的相对贡献；（3）确定专业后来生活中大脑储备机制的决定因素。预计老年人口的两倍 2050年将在美国医疗保健系统上施加巨大的广告相关烧伤。通过提供新颖的见解进入风险和弹性机制，发现可能导致新的策略大大减少这一点通过延迟认知能力下降和阿尔茨海默氏病的发作来负担。