Moran Eileen E, Wang Cuiling, Katz Mindy, Ozelius Laurie, Schwartz Alison, Pavlovic Jelena, Ortega Roberto A, Lipton Richard B, Zimmerman Molly E, Saunders-Pullman Rachel
Department of Psychology, Fordham University, Bronx, NY, USA.
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Neurobiol Aging. 2017 Oct;58:239.e1-239.e7. doi: 10.1016/j.neurobiolaging.2017.06.010. Epub 2017 Jun 24.
Mutations in the glucocerebrosidase (GBA) gene are a strong genetic risk factor for the development of Parkinson's disease and dementia with Lewy Bodies. However the penetrance of GBA mutations is low for these diseases in heterozygous carriers. The aim of this study was to examine the relationship between mutation status and cognitive and motor functioning in a sample of community-dwelling older adults. Using linear mixed effects models, we examined the effect of heterozygous mutation status on 736 community-dwelling older adults (≥70 years) without dementia or Parkinson's disease assessed over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S). Verbal memory was measured using the picture version of the Free and Cued Selective Reminding Test, and carriers showed significantly (p < 0.05) greater decline in verbal memory over time. There was no difference in motor function or any other cognitive domain. Taken together, these results suggest an effect, but an overall limited burden, of harboring a single GBA mutation in aging mutation carriers.
葡萄糖脑苷脂酶（GBA）基因突变是帕金森病和路易体痴呆发生的一个重要遗传风险因素。然而，对于这些疾病，杂合子携带者中GBA突变的外显率较低。本研究的目的是在一组社区居住的老年人样本中，检验突变状态与认知和运动功能之间的关系。我们使用线性混合效应模型，对736名社区居住的≥70岁、无痴呆或帕金森病的老年人进行了平均6年的评估，其中28人有单个GBA突变（主要是N370S），检验杂合突变状态的影响。使用图片版的自由和提示选择性回忆测验测量言语记忆，携带者随时间推移在言语记忆方面表现出显著（p<0.05）更大的下降。运动功能或任何其他认知领域没有差异。综上所述，这些结果表明，在老年突变携带者中携带单个GBA突变有影响，但总体负担有限。
