Department of Psychiatry, Center for Behavioral Genomics.
Department of Psychiatry and Behavioral Neuroscience, University of Chicago.
Psychol Aging. 2014 Jun;29(2):404-17. doi: 10.1037/a0035962.
Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if "memory is memory" and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory.
情景记忆变化是认知老化的一个核心问题,理解这一过程需要阐明其遗传基础。在记忆的遗传信息研究中,一个关键的限制因素是缺乏对遗传和表型复杂性的关注,好像“记忆就是记忆”,所有经过充分验证的评估基本上都是等效的。在这里,我们应用多变量双胞胎模型,对老龄化时代越南双胞胎研究中中老年参与者的数据进行了分析,以检验 3 项标准神经心理学测试中 6 项测量的遗传结构:加利福尼亚词语学习测试-2 以及韦氏记忆量表-III 逻辑记忆(LM)和视觉再现(VR)。双胞胎方法的一个优势是,它可以在不知道具体涉及哪些特定基因的情况下,估计潜在遗传影响在不同测量值之间的共享或独立程度。拟合度最好的模型是一个具有遗传性高阶普遍情景记忆因子和三个测试特定子因子的高阶共同途径模型。更重要的是,特定于潜在 LM 和 VR 子因子的遗传影响(分别为 28%和 30%)以及独立于一般因子的遗传影响,解释了大量的遗传方差。这种独特的遗传影响可以部分解释复制失败的原因。此外,如果不同的基因影响不同的记忆表型,那么它们很可能具有不同的与年龄相关的轨迹。这种方法为提供与衰老和记忆相关的所有类型的遗传信息研究的关键信息迈出了重要的一步。