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

摘要 为了降低阿尔茨海默病（AD）的患病率，科学家和政策制定者呼吁采取新的措施， 疾病的模型。该项目测试了一种新的模型，即文化和基因如何相互作用， 影响AD和认知健康。该项目将提供第一次调查是否可以修改， 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）对不良认知结局的影响，包括AD的风险，以及是否阳性年龄 信念增加了APOE ε2导致有益的认知结果的可能性，包括降低AD风险。 该项目基于我们对老年人的研究结果，即（a）消极的年龄观念可能导致 更大的压力，更差的认知结果，和更大的AD生物标志物积累;和（B）阳性年龄 信念可以保护这些结果。该项目还建立在APOE ε4和ε2 占不到一半的年龄认知方差;年龄信念可能有助于解释其余的方差。 我们提出的老年人项目将首次审查四个具体目标： 目标1.研究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携带者将表现出更大的负面年龄信念对认知能力的不利影响， 结果，与非APOE ε4携带者相比;和（B）APOE ε2携带者将显示更大的有益影响 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.检验我们的年龄信念-APOE基因型模型是否有助于解释种族和性别差异 关于认知结果。考虑到边缘化群体的成员可能对年龄更为敏感， 刻板印象，我们预测：（a）非洲裔美国人将显示出更强的APOE ε4和负的加性影响， 年龄信念对有害的认知结果，以及APOE ε2和正向的更强的加性影响， 与白人相比，对有益认知结果的年龄信念;以及（B）与男性相比，女性将显示 与目标2a中描述的老年非裔美国人相同。 目标3。研究是否心理社会因素，与年龄信念，影响目标1模式。我们预测： (a)脆弱性因素较高的国家（例如，感知歧视）将显示出更强的加性影响， APOE ε4和消极的年龄信念对有害的认知结果，以及较弱的加性影响， APOE ε2和积极的年龄信念对有益的认知结果;和（B）弹性因素较高的那些 (e.g.,对他人有用的感觉）将显示相反的模式。 目标4。研究心理和行为机制是否与年龄信念-基因型预测因子相关 到认知结果。我们预测：压力和体力活动将作为这种关联的中介。 这一拟议项目将利用具有共同关键变量的三个纵向数据集。本研究 符合NIA的优先事项，以确定可能有助于解释不同种族和性别的AD风险差异的因素。

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.