Protective Cognitive Phenotypes in Costa Rica

描述（由申请人提供）：来自我们小组和其他人的证据表明，存在与保护免受认知衰退相关的相对罕见的基因，但鉴定此类基因的努力受到总体缺乏与特定基因可靠相关的有用表型以及可能的遗传异质性的阻碍。然而，一种表型，即90岁以上奥尔兹人的良好认知功能，与家族/遗传保护有关。然而，非痴呆的90岁老人和百岁老人是罕见的，没有真正合适的比较组，与良好的认知功能相关的基因可能与遗传和其他与长寿相关的因素不同。该试点项目的主要目标是为一个更大的（R 01）项目奠定基础，该项目的重点是识别与哥斯达黎加中央谷遗传创始人人群中有痴呆风险的中老年人中罕见保护等位基因的基因相关的神经心理学表型（CVCR）。在哥斯达黎加大学的合作和哥斯达黎加老年医师协会的大力支持下，我们将识别和招募60岁以上的非痴呆性九旬老人和百岁老人先证者及其后代。这些先证者和他们的后代将接受一系列神经心理学测试。这些先证者后代的测试表现将与两组进行比较：a）90岁以上痴呆症患者的60岁以上后代（从而对比了先证者在控制寿命的情况下认知状态的差异）;并且，在本发明中，B）非痴呆个体的60岁以上的兄弟姐妹，他们与第一代后代群体一起生活，但父母的寿命较短（从而对比先证者年龄的差异，同时控制认知状态）。我们假设非痴呆高龄先证者的后代比两个对照组有更好的神经心理功能。最后，一个大大扩大的纵向/遗传研究，使用这个人口将确定新的表型的分子遗传学研究，旨在确定基因的遗传保护性变异。

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.