Successful Cogn. Aging and Cardiovascular Risk Factors in the Central Valley CR

描述(由申请人提供)：对于主要在75岁以下的样本，一些心血管危险因素(CVRF)与认知能力下降、痴呆症和阿尔茨海默病的风险增加有关。尽管经常被解释为普遍适用于所有老年人，但我们小组和其他人的发现表明，在更多的老年人样本中，这种联系大大减少，甚至颠倒。如果正如这些结果所表明的那样，某些CVRF的影响不能反映一生中稳定的心血管风险，那么这些影响可能反映了一些受保护的幸存者所具有的持久特征。或者，它们可能反映了一些老年人在保持良好认知的同时，随着他们进入晚年而发生的适应性变化。R21的目标1将确定这三种成功认知老化模型(SCA；生活至少90年无认知障碍)对心血管危险因素(CVRF)与神经心理表型的关系的适用性。我们将通过比较各自SCA模型所强调的先证者和亲属组来检验CVRF对神经心理表型的影响。该项目将在预期寿命较高、遗传和文化异质性较低的哥斯达黎加进行。在目标2中，目标1的结果将用于在SCA的遗传和表观遗传学基础上设计多位点R01，集中于与每个模型相关的影响CVRF的基因。目标3是在哥斯达黎加现有基础设施的基础上建设研究能力。我们将在这个研究团队中培训有经验和敬业的哥斯达黎加调查人员，这样他们就可以根据这次R21、R01和其他合作项目的数据，在哥斯达黎加进行关于SCA和老龄化的独立研究。

DESCRIPTION (provided by applicant): For samples primarily under 75 years of age, some cardiovascular risk factors (CVRFs) have been associated with increased risk of cognitive decline, dementia, and Alzheimer's disease. Although frequently interpreted as applying generally to all elderly, findings from our group and others suggest that such associations are greatly diminished or even reversed in more elderly samples. If, as these results suggest, the effects of some CVRFs do not reflect stable cardiovascular risk across the life span, these effects may reflect enduring traits possessed by some protected survivors. Alternatively, they may reflect adaptive changes in some elderly as they progress to late old ages while maintaining good cognition. Aim 1 of this R21 will determine the applicability of each of these three models of successful cognitive aging (SCA; living at least 90 years free of cognitive impairment) to the relationships of cardiovascular risk factors (CVRFs) with neuropsychological phenotypes. We will examine the effects of CVRFs on neuropsychological phenotypes by comparing proband and relative groups highlighted by the respective SCA model. The project will be performed in Costa Rica, which has high life expectancy and reduced genetic and cultural heterogeneity. In Aim 2, the Aim 1 results will be used to design a multi-site R01 on the genetic and epigenetic basis of SCA, concentrating on genes affecting CVRFs associated with each model. Aim 3 is to build research capacity in Costa Rica upon an already existing infrastructure. We will train the experienced and dedicated Costa Rican investigators on this research team, so they can perform independent studies of SCA and aging in Costa Rica based on data from this R21, the R01, and other collaborations.