COGNITIVE DECLINE AND THE ROLE OF SPICIFIC GENES

描述（改编自申请人摘要）：拟议研究将 考虑模型和方法来检查遗传和环境的影响 认知能力下降轨迹，包括总遗传 影响和测试特定基因的影响。因为痴呆症可能 代表随着年龄增长而出现的认知变化的一个极端， 同时考虑正常衰老和痴呆， 对规范性认知变化和特定于 痴呆来自788名独特人群样本的认知测量 来自瑞典/收养双胞胎衰老研究和 将利用瑞典双胞胎中的痴呆症;领域将包括 晶体和流体的能力，感知速度和记忆。认知 将使用纵向增长模型估计下降轨迹， 对每个受试者的纵向特征的变化率进行量化， 认知得分我们将研究健康特征之间的联系， 心理社会特征，和测量的易感性基因型（例如，载脂蛋白E，LRP， HLA，其他新兴基因座）与认知能力下降轨迹，利用 目前在双胞胎和同胞对中使用的关联和连锁方法。的 主要兴趣是：（1）认知下降的变化量 轨迹是由显著的风险基因型来解释的？(2)什么量的 下降轨迹的变化是由复杂的物理和 心理社会因素（例如，教育程度，血清脂蛋白水平， 肺功能、吸烟、头部受伤、自我效能）？在重要的 因素，什么是共同的遗传和环境来源的协方差？ (3)基因型与环境是否存在相互作用？例如，执行相同的 (MZ)环境暴露阳性的双胞胎（例如，头部受伤）显示 比没有暴露在环境中的同卵双胞胎下降得更快是 依赖于风险等位基因状态的相互作用（例如，载脂蛋白E 4）？考试 特定的遗传和环境对认知能力下降的影响将导致 增加对导致认知变化的因素的理解， 晚年

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.