Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA.
Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX 75235, USA.
Neuroimage. 2018 Feb 1;166:285-292. doi: 10.1016/j.neuroimage.2017.10.068.
Beta-amyloid (Aβ) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participants (N = 62; aged 51-94) underwent an fMRI spatial distance-judgment task and Amyvid-PET scanning. Voxelwise regression modeled age, linear-Aβ, and quadratic-Aβ as predictors of BOLD activation to difficult spatial distance-judgments. A significant quadratic-Aβ effect on BOLD response explained differential activation in bilateral angular/temporal and medial prefrontal cortices, such that individuals with slightly elevated Aβ burden exhibited hyperactivation whereas even higher Aβ burden was then associated with hypoactivation. Importantly, in high-Aβ individuals, Aβ load moderated the effect of BOLD activation on behavioral task performance, where in lower-elevation, greater deactivation was associated with better accuracy, but in higher-elevation, greater deactivation was associated with poorer accuracy during the task. This study reveals a dose-response, quadratic relationship between increasing Aβ burden and alterations in BOLD activation to cognitive challenge in cognitively-normal individuals that suggests 1) the shift from hyper-to hypo-activation may begin early in disease staging, 2) depends, in part, on degree of Aβ burden, and 3) tracks cognitive performance.
β淀粉样蛋白（Aβ）阳性个体的大脑区域活跃度高于无风险个体；然而，随着阿尔茨海默病症状的开始，这种过度活跃被认为会减少，表现为最终的低活跃度。目前尚不清楚这种转变发生在疾病分期的哪个阶段。我们假设，在认知正常的成年人中，淀粉样蛋白负担的差异水平与大脑激活的增加和减少（即二次轨迹）有关。参与者（N=62；年龄 51-94 岁）接受了 fMRI 空间距离判断任务和 Amyvid-PET 扫描。体素回归模型将年龄、线性 Aβ 和二次 Aβ 作为预测困难空间距离判断时 BOLD 激活的指标。BOLD 反应的二次 Aβ 效应显著，解释了双侧角回/颞叶和内侧前额叶皮质的差异激活，即 Aβ 负担略高的个体表现出过度活跃，而更高的 Aβ 负担则与低活跃度相关。重要的是，在高 Aβ 个体中，Aβ 负荷调节了 BOLD 激活对行为任务表现的影响，在较低的 Aβ 水平下，更大的去激活与更高的准确性相关，但在较高的 Aβ 水平下，更大的去激活与任务期间较差的准确性相关。这项研究揭示了认知正常个体中 Aβ 负担增加与认知挑战时 BOLD 激活改变之间的剂量反应二次关系，表明 1）从过度活跃到低活跃度的转变可能在疾病分期的早期开始，2）部分取决于 Aβ 负担的程度，3）与认知表现相关。
