Scheller Elisa, Schumacher Lena V, Peter Jessica, Lahr Jacob, Wehrle Julius, Kaller Christoph P, Gaser Christian, Klöppel Stefan
Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany.
Freiburg Brain Imaging Center, University of Freiburg, Freiburg, Germany.
Front Aging Neurosci. 2018 Mar 20;10:74. doi: 10.3389/fnagi.2018.00074. eCollection 2018.
Compensation implies the recruitment of additional neuronal resources to prevent the detrimental effect of age-related neuronal decline on cognition. Recently suggested statistical models comprise behavioral performance, brain activation, and measures related to aging- or disease-specific pathological burden to characterize compensation. Higher chronological age as well as the APOE ε4 allele are risk factors for Alzheimer's disease. A more biological approach to characterize aging compared with chronological age is the brain age gap estimation (BrainAGE), taking into account structural brain characteristics. We utilized this estimate in an fMRI experiment together with APOE variant as measures related to pathological burden and aimed at identifying compensatory regions during working memory (WM) processing in a group of 34 healthy older adults. According to published compensation criteria, better performance along with increased brain activation would indicate successful compensation. We examined the moderating effects of BrainAGE on the relationship between task performance and brain activation in prefrontal cortex, as previous studies suggest predominantly frontal compensatory activation. Then we statistically compared them to the effects of chronological age (CA) tested in a previous study. Moreover, we examined the effects of adding APOE variant as a further moderator. Herewith, we strived to uncover neuronal compensation in healthy older adults at risk for neurodegenerative disease. Higher BrainAGE alone was not associated with an increased recruitment in prefrontal cortex. When adding APOE variant as a second moderator, we found an interaction of BrainAGE and APOE variant, such that ε4 carriers recruited right inferior frontal gyrus with higher BrainAGE to maintain WM performance, thus showing a pattern compatible with successful neuronal compensation. Exploratory analyses yielded similar patterns in left inferior and bilateral middle frontal gyrus. These results contrast those from a previous study, where we found no indication of compensation in prefrontal cortex in ε4 carriers with increasing CA. We conclude that BrainAGE together with APOE variant can help to reveal potential neuronal compensation in healthy older adults. Previous results on neuronal compensation in frontal areas corroborate our findings. Compensatory brain regions could be targeted in affected individuals by training or stimulation protocols to maintain cognitive functioning as long as possible.
代偿意味着募集额外的神经元资源，以防止与年龄相关的神经元衰退对认知产生有害影响。最近提出的统计模型包括行为表现、大脑激活以及与衰老或疾病特异性病理负担相关的测量指标，以表征代偿情况。较高的实际年龄以及APOE ε4等位基因是阿尔茨海默病的风险因素。与实际年龄相比，一种更具生物学意义的表征衰老的方法是脑龄差距估计（BrainAGE），它考虑了大脑结构特征。我们在一项功能磁共振成像（fMRI）实验中使用了这种估计方法，并将APOE变体作为与病理负担相关的测量指标，旨在确定一组34名健康老年人在工作记忆（WM）处理过程中的代偿区域。根据已发表的代偿标准，更好的表现以及大脑激活增加将表明代偿成功。我们研究了BrainAGE对前额叶皮质任务表现与大脑激活之间关系的调节作用，因为先前的研究表明主要是额叶代偿性激活。然后我们将它们与先前一项研究中测试的实际年龄（CA）的影响进行统计学比较。此外，我们研究了添加APOE变体作为进一步调节因素的影响。借此，我们努力揭示有神经退行性疾病风险的健康老年人中的神经元代偿情况。单独较高的BrainAGE与前额叶皮质募集增加无关。当添加APOE变体作为第二个调节因素时，我们发现了BrainAGE与APOE变体的相互作用，即ε4携带者在BrainAGE较高时募集右侧额下回以维持WM表现，从而显示出与成功神经元代偿相符的模式。探索性分析在左侧额下回和双侧额中回产生了类似的模式。这些结果与先前一项研究的结果形成对比，在先前的研究中，我们发现随着CA增加，ε4携带者在前额叶皮质中没有代偿迹象。我们得出结论，BrainAGE与APOE变体一起可以帮助揭示健康老年人中潜在的神经元代偿情况。先前关于额叶区域神经元代偿的结果证实了我们的发现。对于受影响的个体，可以通过训练或刺激方案靶向代偿性脑区，以尽可能长时间地维持认知功能。
