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

在这个项目中，我们计划扩大证据表明，寿命是强烈遗传， 长寿的家庭。避免与年龄相关和痴呆相关的认知能力下降是 是成功衰老的关键我们对百岁老人及其后代的研究（LonGenity）导致了 一些长寿基因和相应的表型的鉴定。在横截面上， 显示这些基因型中的一些（例如，胆固醇酯转移蛋白、ApOCS和脂联素）和 表型（例如，HDL水平、脂蛋白颗粒大小分布、脂联素水平）也与 保持认知功能。在此，我们建议扩展并跟踪一组父母的后代 具有异常长寿的（OPEL，n=600）以及具有正常寿命的父母的后代的对照样本 生存率（OPUS，n=600）。两组都将接受每年一次的临床和神经心理学随访。 评估，以确定事件遗忘轻度认知障碍和痴呆。该项目将允许 我们评估了三个水平的暴露变量（异常的父母寿命，寿命 基因型和长寿表型）对两个水平的认知结果变量。利益的结果 这些是记忆和执行功能领域的认知下降以及轻度遗忘 认知障碍（aMCI）和痴呆。我们假设，有特殊遗传病的先证者的后代 长寿的人认知能力下降的速度降低，痴呆和aMCI的发病率降低， 有利的认知结果与特定的长寿基因型和表型相关。临床 核心将收集数据，信息将通过统计和数据 管理核心及其生物信息学共享设施。心血管疾病与其风险之间的相关性 认知下降将通过与项目3的交互进行评估。项目1&2中新发现的基因将 在这项纵向研究中，可以用来检验认知假设。

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.