The Role of Executive Functions in Cognitive Aging and Risk for Mild Cognitive Impairment

执行功能在认知衰老和轻度认知障碍风险中的作用

• 批准号: 10057807
• 负责人: Daniel Gustavson
• 金额: $ 8.65万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057807
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease risk; Anisotropy; Award; Biological; Biological Markers; Brain; Brain imaging; Brain region; Cardiovascular system; Characteristics; Cognition; Cognitive; Cognitive aging; Complex; Data; Data Analyses; Data Set; Dementia; Demographic Factors; Development; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Early identification; Episodic memory; Executive Dysfunction; Funding; Future; Genes; Genetic; Genetic Diseases; Genetic Risk; Genotype; Goals; Health; Heritability; Hylobates Genus; Individual; Inferior; Investigation; Lead; Life; Link; Measures; Medical History; Memory; Memory impairment; Mental Depression; Mental Health; National Institute on Aging; Nature; Nerve Degeneration; Other Genetics; Patients; Performance; Procedures; Process; Prospective Studies; Proxy; Psychopathology; Public Health; Quality of life; Questionnaires; Research; Research Project Grants; Risk; Risk Factors; Role; Sampling; Short-Term Memory; Testing; Time; Twin Multiple Birth; Twin Studies; Vietnam; White Matter Hyperintensity; Work; aging brain; amnestic mild cognitive impairment; base; cardiovascular risk factor; cognitive ability; cognitive change; cognitive control; cognitive process; cognitive reserve; cognitive testing; cost; disorder prevention; executive function; genetic association; improved; indexing; male; middle age; mild cognitive impairment; neuroimaging; normal aging; pathological aging; pre-clinical; psychosocial; relating to nervous system; resilience; response; risk variant; secondary analysis; tool; trait; white matter

PROJECT SUMMARY / ABSTRACT. Efforts to improve treatment of Alzheimer’s disease (AD) are beginning to focus on early identification because diagnosing individuals in the mild cognitive impairment (MCI) stage could improve patient quality of life and substantially reduce the financial impact of the disease. Cognitive assessments in middle age provide ideal early predictors or screeners because they are low cost and non- invasive tools. Although predictive studies of MCI and AD generally focus on episodic memory, executive functions (EFs) are of substantial importance because they control and integrate multiple cognitive processes, and because their performance and associated brain regions are some of the first to decline in middle age. Indeed, there are prominent deficits in EFs in MCI and AD, but few studies have examined these associations longitudinally. We propose that EF deficits can appear as early (or earlier) than memory deficits in the progression to MCI and AD. We will evaluate EFs and memory as predictors of MCI in middle age in combination with another promising early indicator – AD polygenic scores (Aim 1). Genetic risk scores may become highly useful in prospective studies because genotyping procedures are also non-invasive and can be done anytime in life. Specifically, we will examine whether cognitive measures predict MCI more strongly in individuals with high AD genetic risk scores. We will also examine how other early life factors (cognitive reserve) elucidate the associations between EFs, white matter, and AD genetic risk in midlife (Aim 2). We will examine data from the Vietnam Era Twin Study of Aging, which follows a large sample of male twins across 3 time-points in late middle age (mean age 56, 62, and 67; N~1200 at each wave). Twins completed extensive assessment of EFs at all waves (including multiple measures of response inhibition, task-set shifting, working memory, and verbal fluency) as well as multiple measures of other cognitive abilities (including memory), health, and cardiovascular factors. Early adult general cognitive ability (N=1552; our proxy for cognitive reserve) and genotyping (N=1162) are available for most individuals. White matter data are also available for many subjects (N~ 350 to 400 at each wave). The comprehensive cognitive assessment in VETSA allows for the examination of EFs and memory at the level of latent variables, increasing power and generalizability of findings. Moreover, the genetically-informative nature of the sample (i.e., twins and direct genotyping), allows for the decomposition of associations between EFs and white matter into genetic and environmental influences, and examination of the role of AD genetic risk scores in these associations. This award will provide an ideal opportunity to advance our understanding of EFs and cognitive changes across middle age in a rich dataset. Because all research involves secondary analyses of existing data, there will be ample time to achieve the research aims of this proposal. This work will also lead to the development of independently funded projects (e.g., R01) aimed at improving early identification of MCI and AD risk.

项目摘要/摘要。改善阿尔茨海默病(AD)治疗的努力正在开始 关注早期识别，因为诊断处于轻度认知障碍(MCI)阶段的个体 可以改善患者的生活质量，并大大减少疾病对经济的影响。认知 中年评估提供了理想的早期预测或筛查，因为它们成本低，而且不是 侵入性工具。尽管对MCI和AD的预测性研究一般集中在情景记忆、执行 功能(EFS)非常重要，因为它们控制和整合多个认知过程， 因为他们的表现和相关的大脑区域在中年时是最先下降的。 事实上，MCI和AD患者的EFS存在明显的缺陷，但很少有研究检查这些联系 纵向的。我们认为EF缺陷可以比记忆缺陷更早(或更早)出现在 进展为MCI和AD。我们将评估EFS和记忆作为中年MCI的预测因子 结合另一个有希望的早期指标--AD多基因评分(目标1)。遗传风险分数可能 在前瞻性研究中变得非常有用，因为基因分型程序也是非侵入性的，可以 在生活中的任何时候都可以。具体地说，我们将研究认知测量是否能更有力地预测MCI 阿尔茨海默病遗传风险得分高的个体。我们还将研究其他早期生活因素(认知 储备)阐明了EFS、白质和中年AD遗传风险之间的联系(目标2)。 我们将检查越南时期双胞胎老龄化研究的数据，该研究跟踪了大样本的男性双胞胎 中年后期跨越3个时点(平均年龄56、62、67岁，每波N~1200)。双胞胎已完成 对所有波的EFS进行广泛评估(包括反应抑制、任务集转移、 工作记忆和语言流畅性)以及其他认知能力的多种测量(包括 记忆力)、健康和心血管因素。成人早期一般认知能力(N=1552；我们的代名词 认知储备)和基因分型(N=1162)适用于大多数个体。白质数据也是 适用于多个受试者(每波N~350至400)。综合认知测评在中国的应用 Vetsa允许在潜在变量的水平上检查EFS和记忆，增加了能力和 结论的概括性。此外，样本的遗传信息性(即双胞胎和直系 基因分型)，允许将EFS和白质之间的关联分解为遗传和 环境影响，以及AD遗传风险分数在这些关联中的作用的检查。 这一奖项将提供一个理想的机会来促进我们对EFS和认知变化的理解 在一个丰富的数据集中横跨中年。由于所有研究都涉及对现有数据的二次分析，因此 将有充裕的时间来实现这项提案的研究目标。这项工作也将导致 独立资助的项目(例如，R01)，旨在改善对MCI和AD风险的早期识别。