Gordon Brian A, Zacks Jeffrey M, Blazey Tyler, Benzinger Tammie L S, Morris John C, Fagan Anne M, Holtzman David M, Balota David A
Department of Radiology, Washington University in St Louis, St Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St Louis, St Louis, MO, USA.
Department of Radiology, Washington University in St Louis, St Louis, MO, USA; Department of Psychology, Washington University in St Louis, St Louis, MO, USA.
Neurobiol Aging. 2015 May;36(5):1771-9. doi: 10.1016/j.neurobiolaging.2015.01.019. Epub 2015 Jan 29.
There is a growing emphasis on examining preclinical levels of Alzheimer's disease (AD)-related pathology in the absence of cognitive impairment. Previous work examining biomarkers has focused almost exclusively on memory, although there is mounting evidence that attention also declines early in disease progression. In the current experiment, 2 attentional control tasks were used to examine alterations in task-evoked functional magnetic resonance imaging data related to biomarkers of AD pathology. Seventy-one cognitively normal individuals (females = 44, mean age = 63.5 years) performed 2 attention-demanding cognitive tasks in a design that modeled both trial- and task-level functional magnetic resonance imaging changes. Biomarkers included amyloid β42, tau, and phosphorylated tau measured from cerebrospinal fluid and positron emission tomography measures of amyloid deposition. Both tasks elicited widespread patterns of activation and deactivation associated with large task-level manipulations of attention. Importantly, results from both tasks indicated that higher levels of tau and phosphorylated tau pathologies were associated with block-level overactivations of attentional control areas. This suggests early alteration in attentional control with rising levels of AD pathology.
在无认知障碍的情况下，对阿尔茨海默病（AD）相关病理的临床前水平进行检测的重视程度日益增加。以往对生物标志物的研究几乎完全集中在记忆方面，尽管越来越多的证据表明，在疾病进展早期注意力也会下降。在当前实验中，使用了两项注意力控制任务来检测与AD病理生物标志物相关的任务诱发功能磁共振成像数据的变化。71名认知正常个体（女性 = 44名，平均年龄 = 63.5岁）在一个模拟试验级和任务级功能磁共振成像变化的设计中执行了两项需要注意力的认知任务。生物标志物包括从脑脊液中测得的淀粉样β42、tau和磷酸化tau，以及淀粉样蛋白沉积的正电子发射断层扫描测量。两项任务都引发了与注意力在任务水平上的大幅操作相关的广泛激活和去激活模式。重要的是，两项任务的结果均表明，较高水平的tau和磷酸化tau病理与注意力控制区域在组块水平上的过度激活有关。这表明随着AD病理水平的升高，注意力控制会出现早期改变。
