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: 10728182
• 负责人: Daniel Gustavson
• 金额: $ 4.69万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10728182
• 关键词: Role; Executive; Functions; Cognitive; Aging

PROJECT SUMMARY 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.

项目概要 改善阿尔茨海默病 (AD) 治疗的努力开始集中于早期识别 因为在轻度认知障碍 (MCI) 阶段诊断个体可以提高患者的治疗质量 生命并大幅减少疾病的经济影响。中年认知评估提供 理想的早期预测器或筛查器，因为它们是低成本且非侵入性的工具。虽然有预见性 MCI 和 AD 的研究通常集中于情景记忆，执行功能 (EF) 具有重要意义。 重要性，因为它们控制和整合多个认知过程，并且因为它们的表现 和相关的大脑区域是中年时期最先衰退的区域。确实有突出的 MCI 和 AD 中的 EF 缺陷，但很少有研究纵向检验这些关联。我们建议 在 MCI 和 AD 的进展过程中，EF 缺陷可能比记忆缺陷早（或更早）出现。我们 将评估 EF 和记忆力作为中年 MCI 的预测因素，并与另一种有前途的早期预测相结合 指标——AD 多基因评分（目标 1）。遗传风险评分可能在前瞻性研究中非常有用 因为基因分型程序也是非侵入性的，可以在生命中的任何时候进行。具体来说，我们将 检查认知测量是否对 AD 遗传风险高的个体更能预测 MCI 分数。我们还将研究其他早期生活因素（认知储备）如何阐明这些关联 EF、白质和中年 AD 遗传风险之间的关系（目标 2）。 我们将检查越南时代双胞胎衰老研究的数据，该研究跟踪了大量男性双胞胎样本 跨越中年晚期的 3 个时间点（平均年龄 56、62 和 67；每波 N~1200）。双胞胎完成 对所有波的 EF 进行广泛评估（包括反应抑制的多种测量、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衡量标准 （包括记忆力）、健康和心血管因素。早期成人一般认知能力（N=1552；我们的 大多数人都可以使用认知储备代理）和基因分型（N=1162）。白质数据是 也适用于许多科目（每波 N~ 350 至 400）。综合认知评估 VETSA 允许在潜在变量级别检查 EF 和内存，从而提高能力和 研究结果的普遍性。此外，样本的遗传信息性质（即双胞胎和直系亲属） 基因分型），允许将 EF 和白质之间的关联分解为遗传和 环境影响，并检查 AD 遗传风险评分在这些关联中的作用。 该奖项将为增进我们对 EF 和认知变化的理解提供一个理想的机会 在丰富的数据集中跨越中年。由于所有研究都涉及对现有数据的二次分析，因此 将有充足的时间来实现本提案的研究目标。这项工作也将促进发展 旨在改进 MCI 和 AD 风险的早期识别的独立资助项目（例如 R01）。