PHENOTYPE & GENOTYPE FOR EXEPTIONAL LONGEVITY & THE PREVENTION OF COGNITIVE DECLI

在这个计划项目中，我们计划扩大证据，表明寿命在 特别长寿的家庭。避免年龄相关和痴呆症相关的认知能力下降是 对成功的衰老至关重要。我们对百岁老人及其后代(LonGenity)的研究导致了 鉴定了一些长寿基因和相应的表型。在横截面上，我们有 研究表明，这些基因型中的一些(如胆固醇酯转移蛋白、载脂蛋白和脂联素)和 表型(如高密度脂蛋白水平、脂蛋白颗粒大小分布、脂联素水平)也与 认知功能的保存。在此，我们建议扩大和跟踪父母的后代队列 超乎寻常的长寿(欧宝，n=600)，以及正常父母的后代的对照样本 存活(OPUS，n=600)。两组都将每年进行面对面的临床和神经心理学检查。 评估以确定事件遗忘性轻度认知障碍和痴呆。该项目将允许 美国评估三个水平的暴露变量(特殊的双亲寿命、长寿)的贡献 基因类型和长寿表型)在认知结果变量的两个水平。感兴趣的结果 以下是记忆和执行功能领域的认知衰退，以及健忘症轻度 认知障碍(AMCI)和痴呆症。我们假设先证者的后代有特殊的 长寿会降低认知功能减退率，降低痴呆症和急性脑梗塞的发病率，而且 良好的认知结果与特定的长寿基因和表型有关。《临床》 核心将收集数据，并将通过统计和数据提供信息 管理核心及其生物信息学共享设施。心血管疾病与其风险的相关性 认知能力下降将通过与项目3的互动进行评估。项目1和2中新发现的基因将 可用于检验这项纵向研究中的认知假说。

In this Program Project we plan to expand the evidence indicating that life span is strongly inherited in families with exceptional longevity. Avoiding age-related and dementia-related cognitive decline are essential to successful aging. Our studies of centenarians and their offspring (LonGenity) have lead to the identification of a number of longevity genes and corresponding phenotypes. At cross-section, we have shown that some of these genotypes (e.g., cholesterol ester transfer protein, ApOCS and adiponectin) and phenotypes (e.g., HDL level, lipoprotein particle size distribution, adiponectin level) are also associated with preservation of cognitive function. Herein, we propose to expand and follow a cohort of offspring of parents with exceptional longevity (OPEL, n=600) as well as a control sample of offspring of parents with usual survival (OPUS, n=600). Both groups will be followed with annual in-person clinical and neuropsychological assessments to identify incident amnestic Mild Cognitive Impairment and dementia. This project will allows us to assess the contribution of three levels of exposure variables (exceptional parental longevity, longevity genotypes and longevity phenotypes) on two levels of cognitive outcomevariables. The outcomes of interest here are cognitive decline in the domains of memory and executive function as well as amnestic Mild Cognitive Impairment (aMCI) and dementia. We hypothesize that offspring of probands with exceptional longevity have a reduced rate of cognitive decline and a reduced incidence of dementia and aMCI and that favorable cognitive outcomes are associated with specific longevity genotypes and phenotypes. The Clinical Core will collect the data and information will be made available through the Statistics and Data Management Core and its Bioinformatics Sharing facility. The correlation between CVD and its risks with cognitive decline will assess through interaction with project 3. Newly discovered genes in projects 1&2 will be made available for testing cognitive hypotheses in this longitudinal study.