Li Jinghang, Mountz Elizabeth J, Mizuno Akiko, Shah Ashti M, Weinstein Andrea, Cohen Ann D, Klunk William E, Snitz Beth E, Aizenstein Howard J, Karim Helmet T
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
J Alzheimers Dis. 2023;95(3):1077-1089. doi: 10.3233/JAD-230379.
Amyloid-β (Aβ) deposits asymmetrically early in Alzheimer's disease (AD). This process is variable and has been associated with asymmetric hypometabolism.
We investigated whether neural asymmetry during working memory and executive function processing was associated with AD genetic risk and markers of AD as well as other brain neuropathology biomarkers, cognitive function, and cognitive reserve in cognitively normal older adults.
We analyzed data from 77 cognitively healthy, older adults who completed functional magnetic resonance imaging, positron emission tomography, and cognitive testing. We identified regions of significant activation and asymmetry during the Digital Symbol Substitution Task (DSST). We examined associations between regions with significant hemispheric asymmetry (directional and absolute) and global cerebral Aβ, cerebral glucose metabolism, white matter hyperintensities, APOE ɛ4 allele status, DSST reaction time, age, sex, education, and cognitive function.
Asymmetry was not associated with several factors including cognitive function, Aβ, and white matter hyperintensities. The presence of at least one ɛ4 APOE allele in participants was associated with less asymmetric activation in the angular gyrus (right dominant activation). Greater education was associated with less asymmetric activation in mediodorsal thalamus (left dominant activation).
Genetic risk of AD was associated with lower asymmetry in angular gyrus activation, while greater education was associated with lower asymmetry in mediodorsal thalamus activation. Changes in asymmetry may reflect components of compensation or cognitive reserve. Asymmetric neural recruitment during working memory may be related to maintenance of cognitive function in cognitively normal older adults.
β淀粉样蛋白（Aβ）在阿尔茨海默病（AD）早期不对称沉积。这一过程具有变异性，且与不对称性代谢减退有关。
我们调查了认知功能正常的老年人在工作记忆和执行功能处理过程中的神经不对称性是否与AD遗传风险、AD标志物以及其他脑病理学生物标志物、认知功能和认知储备相关。
我们分析了77名认知健康的老年人的数据，这些老年人完成了功能磁共振成像、正电子发射断层扫描和认知测试。我们在数字符号替换任务（DSST）中确定了显著激活和不对称的区域。我们检查了具有显著半球不对称性（方向性和绝对不对称性）的区域与全脑Aβ、脑葡萄糖代谢、白质高信号、APOEε4等位基因状态、DSST反应时间、年龄、性别、教育程度和认知功能之间的关联。
不对称性与包括认知功能、Aβ和白质高信号在内的多个因素无关。参与者中至少存在一个ɛ4 APOE等位基因与角回中不对称激活减少有关（右侧为主导激活）。受教育程度越高与背内侧丘脑不对称激活减少有关（左侧为主导激活）。
AD的遗传风险与角回激活的较低不对称性有关，而受教育程度越高与背内侧丘脑激活的较低不对称性有关。不对称性的变化可能反映了代偿或认知储备的组成部分。工作记忆期间的不对称神经募集可能与认知功能正常的老年人认知功能的维持有关。
