University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA.
Department of Psychology, University of Kansas, Lawrence, KS, USA.
J Alzheimers Dis. 2019;70(4):1059-1068. doi: 10.3233/JAD-190293.
TOMM40 '523 is associated with Alzheimer's disease (AD), but APOE linkage disequilibrium confounds this association. In 170 APOE ɛ3 homozygotes, we evaluated relationships between short and very long TOMM40 alleles and longitudinal declines in three cognitive domains (attention, verbal memory, and executive function). We used factor analysis to create composite scores from 10 individual cognitive tests, and latent growth curve modeling adjusting for clinical status (normal, amnestic mild cognitive impairment, or AD) to summarize initial performance and change over three years. Relative to individuals with two very long TOMM40 alleles, APOEɛ3 homozygotes with one or two short alleles showed lower baseline cognitive performance regardless of clinical status. The number of short or very long TOMM40 alleles was not associated with longitudinal cognitive changes. In APOEɛ3 homozygotes from the University of Kansas Alzheimer's Disease Center cohort, an association between TOMM40 '523 and cognition is consistent with the possibility that TOMM40 influences cognition independent of APOE.
TOMM40 '523 与阿尔茨海默病（AD）相关，但 APOE 连锁不平衡使这种关联复杂化。在 170 名 APOE ɛ3 纯合子中，我们评估了短和非常长的 TOMM40 等位基因与三个认知领域（注意力、言语记忆和执行功能）的纵向下降之间的关系。我们使用因子分析从 10 项个体认知测试中创建综合评分，并使用潜在增长曲线模型调整临床状况（正常、遗忘型轻度认知障碍或 AD），以总结初始表现和三年内的变化。与具有两个非常长的 TOMM40 等位基因的个体相比，无论临床状况如何，具有一个或两个短等位基因的 APOEɛ3 纯合子的基线认知表现较低。短或非常长的 TOMM40 等位基因的数量与纵向认知变化无关。在来自堪萨斯大学阿尔茨海默病中心队列的 APOEɛ3 纯合子中，TOMM40 '523 与认知之间的关联符合 TOMM40 独立于 APOE 影响认知的可能性。
