Culture-Gene Relationship: A Novel Model of Aging Cognitive Health

文化与基因的关系：老龄化认知健康的新模型

• 批准号: 9311065
• 负责人: BECCA R LEVY
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9311065
• 关键词: African American; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Apolipoproteins; Autopsy; Baltimore; Behavioral Mechanisms; Belief; Biological Markers; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Data; Data Set; Dementia; Diagnosis; Discrimination; Disease; Disease model; Elderly; Environmental Risk Factor; Feeling; Fibrinogen; Genes; Genotype; Health; Health Status; Health and Retirement Study; Hippocampus (Brain); Impaired cognition; Individual; Intervention; Investigation; Lead; Link; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Mental Depression; Modeling; National Institute on Aging; Neurofibrillary Tangles; Outcome; Pattern; Physical activity; Policy Maker; Predisposition; Prevalence; Psychosocial Factor; Race; Research; Risk; Scientist; Senile Plaques; Stereotyping; Stress; Susceptibility Gene; Testing; Time; Veterans; Woman; apolipoprotein E-4; base; cognitive performance; experience; genetic risk factor; improved; longitudinal dataset; member; men; mild cognitive impairment; novel; primary outcome; psychologic; psychosocial; racial disparity; resilience; secondary outcome; sex; theories; young adult

Abstract To reduce the prevalence of Alzheimer's disease (AD), scientists and policy makers have called for new models of the disease. The proposed project tests a novel model of how culture and genes may interact to influence AD and cognitive health. This project will provide the first investigation of whether a modifiable, culture-based environmental factor, negative age beliefs, exacerbates the effect of the genetic-risk-factor apolipoprotein E4 (APOE ε4) on adverse cognitive outcomes, including risk for AD, and whether positive age beliefs increase the likelihood that APOE ε2 leads to beneficial cognitive outcomes, including reduced AD risk. The proposed project builds on our findings with older individuals that (a) negative age beliefs can lead to greater stress, worse cognitive outcomes, and a greater accumulation of AD biomarkers; and (b) positive age beliefs can protect against these outcomes. This project also builds on the finding that APOE ε4 and ε2 account for less than half of aging-cognition variance; age beliefs may help to explain the remaining variance. Our proposed project with older persons will examine four specific aims for the first time: Aim 1. To examine whether the APOE genotype moderates age beliefs' impact on cognitive outcomes. We predict: (a) APOE ε4 carriers will show a greater detrimental impact of negative age beliefs on cognitive outcomes, compared to non-APOE ε4 carriers; and (b) APOE ε2 carriers will show a greater beneficial impact of positive age beliefs on cognitive outcomes, compared to non-APOE ε2 carriers. Aim 2. To examine whether our age belief-APOE genotype model helps to explain disparities by race and sex on cognitive outcomes. Considering that members of marginalized groups may be more sensitive to age stereotypes, we predict: (a) African Americans will show a stronger additive influence of APOE ε4 and negative age beliefs on detrimental cognitive outcomes, as well as a stronger additive influence of APOE ε2 and positive age beliefs on beneficial cognitive outcome, compared to Whites; and (b) women, compared to men, will show the same pattern as older African Americans described in Aim 2a. Aim 3. To examine whether psychosocial factors, related to age beliefs, influence Aim 1 patterns. We predict: (a) those higher in vulnerability factors (e.g., perceived discrimination) will show a stronger additive influence of APOE ε4 and negative age beliefs on detrimental cognitive outcomes, as well as a weaker additive influence of APOE ε2 and positive age beliefs on beneficial cognitive outcomes; and (b) those higher in resiliency factors (e.g., feeling useful to others) will show the reverse pattern. Aim 4. To examine whether psychological and behavioral mechanisms link the age belief-genotype predictor to cognitive outcomes. We predict: stress and physical activity will act as mediators of this association. This proposed project will draw on three longitudinal datasets with common key variables. This study meets the NIA priority to identify factors that could help explain disparities in AD risk by race and sex.

抽象的 为了减少阿尔茨海默病 (AD) 的患病率，科学家和政策制定者呼吁采取新的措施 该疾病的模型。拟议的项目测试了文化和基因如何相互作用的新模型 影响 AD 和认知健康。该项目将首次调查是否可修改， 基于文化的环境因素、消极的年龄信念，加剧了遗传风险因素的影响 载脂蛋白 E4 (APOE ε4) 对不良认知结果的影响，包括 AD 风险，以及是否阳性年龄 信念增加了 APOE ε2 带来有益认知结果的可能性，包括降低 AD 风险。 拟议的项目建立在我们对老年人的调查结果之上，即（a）消极的年龄信念可能导致 更大的压力、更差的认知结果以及更多的 AD 生物标志物积累； (b) 正年龄 信念可以防止这些结果。该项目还建立在 APOE ε4 和 ε2 的发现基础上 占衰老认知差异的不到一半；年龄信念可能有助于解释剩余的差异。 我们提议的老年人项目将首次审查四个具体目标： 目标 1. 检验 APOE 基因型是否调节年龄信念对认知结果的影响。我们 预测：(a) APOE ε4 携带者将表现出负面年龄信念对认知的更大有害影响 与非 APOE ε4 携带者相比的结果； (b) APOE ε2 载体将显示出更大的有益影响 与非 APOE ε2 携带者相比，积极的年龄信念对认知结果的影响。 目标 2. 检查我们的年龄信念-APOE 基因型模型是否有助于解释种族和性别的差异 关于认知结果。考虑到边缘群体的成员可能对年龄更敏感 刻板印象，我们预测：（a）非洲裔美国人将表现出更强的 APOE ε4 和负面影响 年龄信念对有害认知结果的影响，以及 APOE ε2 和积极认知的更强附加影响 与白人相比，年龄对有益认知结果的信念； (b) 与男性相比，女性会表现出 与目标 2a 中描述的年长非裔美国人的模式相同。 目标 3. 检验与年龄信念相关的心理社会因素是否影响目标 1 模式。我们预测： (a) 脆弱性因素（例如，感知到的歧视）较高的人将表现出更强的附加影响 APOE ε4 和消极的年龄信念对有害的认知结果以及较弱的附加影响 APOE ε2 和对有益认知结果的积极年龄信念； (b) 弹性系数较高的人 （例如，感觉对他人有用）会表现出相反的模式。 目标 4. 检查心理和行为机制是否与年龄信念基因型预测因素相关 认知结果。我们预测：压力和体力活动将充当这种关联的中介。 该拟议项目将利用三个具有共同关键变量的纵向数据集。这项研究 符合 NIA 的优先事项，即确定有助于解释种族和性别 AD 风险差异的因素。