Protective Cognitive Phenotypes in Costa Rica

描述（由申请人提供）：来自我们团队和其他人的证据表明，存在相对罕见的与认知衰退保护相关的基因，但由于总体上缺乏与特定基因可靠地相关的有用表型，以及可能的遗传异质性，鉴定这些基因的努力受到阻碍。然而，有一种表型，即90岁以上老年人良好的认知功能，与家族/遗传保护有关。然而，无痴呆的百岁老人和百岁老人非常罕见，没有真正合适的对照组，与良好认知功能相关的基因可能与与长寿相关的遗传和其他因素不同。该试点项目的主要目标是为一个更大的（R01）项目奠定基础，该项目专注于识别哥斯达黎加中央山谷（CVCR）遗传创始人群中具有痴呆风险的中老年个体中与罕见保护性等位基因相关的神经心理表型。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，我们将确定和招募年龄在60岁以上的无痴呆的百岁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通过一系列神经心理学测试进行评估。将这些先证者后代的测试表现与两组进行比较：a)老年痴呆患者的60岁以上后代（从而对比先证者在控制寿命的情况下认知状况的差异）；b)非痴呆个体的60岁以上的兄弟姐妹年龄与主要后代组相当，但父母寿命较短（从而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，非痴呆的高龄先证者的后代将比两个对照组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/遗传研究将为分子遗传学研究确定新的表型，旨在确定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.