Stickel Ariana, Kawa Kevin, Walther Katrin, Glisky Elizabeth, Richholt Ryan, Huentelman Matt, Ryan Lee
Cognition and Neuroimaging Laboratory, Department of Psychology, University of Arizona, Tucson, AZ, United States.
Epilepsy Center Erlangen, Department of Neurology, University Hospital Erlangen, Erlangen, Germany.
Front Aging Neurosci. 2018 Jan 10;9:431. doi: 10.3389/fnagi.2017.00431. eCollection 2017.
The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, = 38), young old (ages 65-72, = 45), and older old (ages 73-92, = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither nor the interaction between and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.
资源调节假说表明，基因对认知功能的影响会随着年龄的增长而增加。与情景记忆和工作记忆相关的单核苷酸多态性rs17070145被认为遵循这样一种模式，但很少有研究直接验证这一论断。本研究调查了三组认知健康的成年人（中年组，年龄52 - 64岁，n = 38；年轻老年组，年龄65 - 72岁，n = 45；老年老年组，年龄73 - 92岁，n = 62）的等位基因（T携带者与CC纯合子）、认知表现和脑容量之间的关系，这些组在包括载脂蛋白ε4状态和高血压等潜在混杂变量上进行了仔细匹配。与我们的预测一致，T携带者随着年龄增长保持言语记忆表现，而CC纯合子则下降。基于体素的磁共振图像形态学分析显示，T携带者在额叶白质体积方面具有优势，且这种优势随着年龄增长而增加。聚焦于老年老年组，T携带者在左侧舌回灰质和其他几个额叶白质区域也具有这种优势。与预期相反，等位基因以及等位基因与年龄之间的交互作用均未预测海马体体积。所研究的脑区均未显示出CC纯合子的优势。综上所述，这些数据表明，与T携带者相比，CC纯合子会导致言语记忆表现下降和脑容量降低，尤其是在最年长的人群中，这与资源调节假说一致。
