COGNITIVE DECLINE AND THE ROLE OF SPICIFIC GENES

描述(改编自申请人的摘要)：拟议的研究将 考虑检验遗传和环境影响的模型和方法 关于认知衰退的轨迹，包括两个估计的总基因 特定基因效应的影响和检验。因为痴呆症可能 代表了随着年龄的增长而出现的认知变化的一个极端，方法是 同时考虑正常衰老和痴呆症，并发现串联 对规范性认知变化的影响以及特定于 痴呆症。来自788个独特总体样本的认知测量 瑞典/领养双胞胎年龄研究和双胞胎研究 将利用瑞典双胞胎中的痴呆症；领域将包括 结晶和流动的能力，感知速度和记忆力。认知 下降轨迹将使用纵向增长模型进行估计，其中 每个受试者的纵向轮廓的变化率被量化 认知分数。我们将研究健康特征之间的关联， 心理社会特征和测量的易感基因类型(例如，APOE，LRP， 其他正在出现的基因座)具有认知衰退轨迹，利用 目前在双胞胎和同胞对中使用的关联和连锁方法。的 本金利息是：(1)认知衰退的变异量是多少 轨迹是由显著的风险基因类型解释的吗？(2)多少 下降轨迹的变化是由复杂的物理和 社会心理因素(例如，教育程度、血清脂蛋白水平、 肺功能、吸烟、头部损伤、自我效能)？在重要的 因素，协方差的共同遗传和环境来源是什么？ (3)是否存在基因-环境互作？例如，执行相同的操作 (MZ)双胞胎环境暴露阳性(如头部受伤) 比没有暴露在环境中的同卵双胞胎下降更多吗？是 相互作用依赖于风险等位基因状态(例如，载脂蛋白4)？考试 特定的遗传和环境对认知能力下降的影响将导致 对导致认知变化的因素有更深入的了解 晚年生活。

DESCRIPTION (Adapted from the Applicant's Abstract): The proposed study will consider models and methods to examine the genetic and environmental influences on cognitive decline trajectories, including both estimates of total genetic influence and tests of the effects of specific genes. Because dementia may represent one extreme of cognitive changes seen with advancing age, methods are used that simultaneously consider normal aging and dementia and uncover tandem influences on both normative cognitive change and those effects specific to dementia. Cognitive measures from a unique population based sample of 788 same-sex twins from the Swedish/Adoption Twin Study of Aging and the Study of Dementia in Swedish Twins will be utilized; domain areas will include crystallized and fluid abilities, perceptual speed and memory. Cognitive decline trajectories will be estimated using longitudinal growth models where rate of change is quantified for each subjects' longitudinal profile of cognitive scores. We will examine the association of health traits, psychosocial traits, and measured susceptibility genotypes (e.g., APOE, LRP, HLA, other emerging loci) with cognitive decline trajectories, making use of current association and linkage methods utilized in twin and sib-pairs. Of principal interest are: (1) What amount of variation in cognitive decline trajectories is explained by significant risk genotypes? (2) What amount of variation in decline trajectories is explained by complex physical and psychosocial factors (e.g., educational attainment, serum lipoprotein levels, pulmonary function, smoking, head injury, self-efficacy)? Among significant factors, what are the shared genetic and environmental sources of covariance? (3) Are genotype-environment interactions present? For example, do identical (MZ) twins positive for environmental exposures (e.g., head injury) show greater decline than their co-twins without the environmental exposure? Is the interaction dependent on risk allele status (e.g., APOE 4)? The examination specific genetic and environmental influences on cognitive decline will lead to an increased understanding of factors that contribute to cognitive changes in late-life.