β-淀粉样蛋白积累对成年期编码过程中神经功能的影响。

Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan.

机构信息

Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, 1600 Viceroy Dr., Ste 800, Dallas, TX 75235, USA.

出版信息

Neuroimage. 2012 Aug 1;62(1):1-8. doi: 10.1016/j.neuroimage.2012.03.077. Epub 2012 May 1.

Abstract

Limited functional imaging evidence suggests that increased beta-amyloid deposition is associated with alterations in brain function, even in healthy older adults. However, the majority of these findings report on resting-state activity or functional connectivity in adults over age 60. Much less is known about the impact of beta-amyloid on neural activations during cognitive task performance, or the impact of amyloid in young and middle-aged adults. The current study measured beta-amyloid burden from PET imaging using (18)Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89 years). The same participants also underwent fMRI scanning, performing a memory encoding task. Using both beta-amyloid burden and age as continuous predictors of encoding activity, we report a dose-response relationship of beta-amyloid load to neural function, beyond the effects of age. Specifically, individuals with greater amyloid burden evidence less neural activation in bilateral dorsolateral prefrontal cortex, a region important for memory encoding, as well as reduced neural modulation in areas associated with default network activity: bilateral superior/medial frontal and lateral temporal cortex. Importantly, this reduction of both activation and suppression as a function of amyloid load was found across the lifespan, even in young- and middle-aged individuals. Moreover, this frontal and temporal amyloid-reduced activation/suppression was associated with poorer processing speed, verbal fluency, and fluid reasoning in a subgroup of individuals with elevated amyloid, suggesting that it is detrimental, rather than compensatory in nature.

摘要

有限的功能影像学证据表明,β-淀粉样蛋白沉积的增加与大脑功能的改变有关,即使在健康的老年人中也是如此。然而,这些发现中的大多数都报告了 60 岁以上成年人的静息状态活动或功能连接。关于β-淀粉样蛋白对认知任务表现期间神经激活的影响,或在年轻和中年成年人中淀粉样蛋白的影响,人们知之甚少。本研究使用 (18)Florbetapir 通过 PET 成像测量了β-淀粉样蛋白负荷,在一个由高度筛选的健康成年人(N=137;年龄 30-89 岁)组成的大型连续年龄样本中。同一组参与者还接受了 fMRI 扫描,执行记忆编码任务。使用β-淀粉样蛋白负荷和年龄作为编码活动的连续预测因子,我们报告了β-淀粉样蛋白负荷与神经功能之间的剂量反应关系,这种关系超出了年龄的影响。具体来说,β-淀粉样蛋白负荷较大的个体在双侧背外侧前额叶皮层中表现出较少的神经激活,而背外侧前额叶皮层是记忆编码的重要区域,以及与默认网络活动相关的区域的神经调节减少:双侧额上/内侧额叶和外侧颞叶皮层。重要的是,即使在年轻和中年个体中,这种随淀粉样蛋白负荷的增加而减少的激活和抑制作用也存在于整个生命周期中。此外,这种额叶和颞叶淀粉样蛋白减少的激活/抑制与处理速度、言语流畅性和流体推理能力较差有关,这在一组淀粉样蛋白水平升高的个体中更为明显,这表明这种激活/抑制是有害的,而不是代偿性的。

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