Protective Cognitive Phenotypes in Costa Rica

描述(申请人提供)：来自我们小组和其他人的证据表明，存在与防止认知衰退相关的相对罕见的基因，但识别此类基因的努力受到阻碍，因为总体上缺乏与特定基因可靠相关的有用表型，这些基因可以增强对认知衰退的保护，以及可能的遗传异质性。然而，一种表型，在90岁以上的人中认知功能良好，与家庭/基因保护有关。然而，非痴呆的非老年人和百岁老人很少见，没有真正合适的比较组，而且与良好认知功能相关的基因很可能不同于与长寿有关的遗传和其他因素。这个试点项目的主要目标是为一个更大的(R01)项目创造基础，该项目专注于在哥斯达黎加中央山谷(CVCR)的遗传创始人群体(CVCR)中识别与具有罕见保护性等位基因的中老年个体痴呆风险的基因相关的神经心理学表型。在哥斯达黎加大学的合作和哥斯达黎加老年医师学会的大力支持下，我们将确定和招募60岁以上的非痴呆症非老年者和百岁先驱及其后代。这些先证者及其后代将接受一系列神经心理测试的评估。这些先证者的后代的测试表现将与两组进行比较：a)患有精神错乱的非老年者的60岁以上的后代(因此在控制寿命时对比先证者认知状态的差异)；以及b)与主要子女组年龄相当但非痴呆者父母寿命较短的60岁以上的非痴呆者的兄弟姐妹(因此在控制认知状态的情况下对比先证者的年龄差异)。我们假设，与两个对照组相比，非痴呆症高龄先证者的后代具有更好的神经心理功能。最终，利用这一群体进行的大规模纵向/遗传学研究将为分子遗传学研究识别新的表型，目的是识别具有遗传保护变异的基因。

DESCRIPTION (provided by applicant): Evidence from our group and others indicate the presence of relatively rare genes associated with protection from cognitive deterioration, but efforts to identify such genes are hampered by the overall absence of useful phenotypes reliably associated with specific genes conferring increased protection from cognitive decline as well as likely genetic heterogeneity. One phenotype, however, good cognitive functioning in 90+ year olds, has been associated with familial/genetic protection. Nevertheless, nondemented nonagenarians and centenarians are rare, have no truly appropriate comparison group, and genes associated with good cognitive functioning may well be different than genetic and other factors associated with longevity. The major goal of this pilot project is to create the groundwork for a larger (R01) project focused on identifying neuropsychological phenotypes associated with genes with infrequent protective alleles in moderately elderly individuals at risk for dementia in the genetic founder population of the Central Valley of Costa Rica (CVCR). With the collaboration of the University of Costa Rica and the strong support of the Costa Rican Society of Geriatric Physicians, we will identify and recruit nondemented nonagenarians and centenarian probands and their offspring who are 60+ years of age. These probands and their offspring will be assessed on a battery of neuropsychological tests. The test performance in the offspring of these probands will be compared with two groups: a) the 60+ year old offspring of demented nonagenarians (thus contrasting on the difference in the proband's cognitive status while controlling for longevity); and, b) the 60+ year old siblings of nondemented individuals comparably aged to the primary offspring group but with shorter lived nondemented parents (thus contrasting the difference in the proband's age while controlling for cognitive status). We hypothesize that offspring of non-demented very elderly probands will have better neuropsychological functioning than the two comparison groups. Ultimately, a greatly enlarged longitudinal/genetic study using this population will identify new phenotypes for molecular genetic studies aimed at identifying genes with genetic protective variants.