Scheller Elisa, Peter Jessica, Schumacher Lena V, Lahr Jacob, Mader Irina, Kaller Christoph P, Klöppel Stefan
Department of Psychiatry, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Freiburg Brain Imaging Center (FBI), University Medical Center Freiburg, Freiburg, Germany.
Department of Psychiatry, Faculty of Medicine, University of Freiburg, Freiburg, Germany; University Hospital of Old Age Psychiatry and Psychotherapy Bern, Bern, Switzerland.
Neurobiol Aging. 2017 Aug;56:127-137. doi: 10.1016/j.neurobiolaging.2017.04.015. Epub 2017 Apr 26.
The APOE ε4 allele increases the risk for sporadic Alzheimer's disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers' working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimer's disease-relevant brain areas before cognitive decline. Moreover, we identified ε4 carriers to show higher activations in task-negative medial and task-positive inferior frontal areas along with better performance under high working memory load relative to non-ε4 carriers. The increased frontal recruitment is compatible with models of neuronal compensation, extends on existing evidence, and suggests that ε4 carriers require additional neuronal resources to successfully perform a demanding working memory task.
APOE ε4等位基因会增加散发性阿尔茨海默病的风险，并改变众多认知领域的大脑激活模式。我们使用字母n-back任务评估认知功能完好的老年人，以确定先前观察到的ε4携带者与工作记忆相关的大脑激活增加是否具有代偿作用，从而有助于维持工作记忆功能。我们使用多元回归模型，独立于任务表现确定了双侧海马体中APOE变体与年龄的相互作用：ε4携带者仅随着年龄增长而出现激活减少，这表明功能磁共振成像（fMRI）数据在检测认知衰退之前与阿尔茨海默病相关脑区变化方面具有高敏感性。此外，我们发现ε4携带者在任务负性内侧区域和任务正性额下回区域表现出更高的激活，并且相对于非ε4携带者，在高工作记忆负荷下表现更好。额叶募集增加与神经元代偿模型相符，扩展了现有证据，并表明ε4携带者需要额外的神经元资源来成功完成要求较高的工作记忆任务。
