Abnormal deposition of Aβ amyloid is an early neuropathological marker of Alzheimer’s disease (AD), arising long ahead of clinical symptoms. Non-invasive measures of associated early neurofunctional changes, together with easily accessible behavioral readouts of these changes, could be of great clinical benefit. We pursued this aim by investigating large-scale cortical gradients of functional connectivity with functional MRI, which capture the hierarchical integration of cortical functions, together with acoustic-prosodic features from spontaneous speech, in cognitively unimpaired older adults with and without Aβ positivity (total N = 188). We predicted distortions of the cortical hierarchy associated with prosodic changes in the Aβ + group. Results confirmed substantially altered cortical hierarchies and less variability in these in the Aβ + group, together with an increase in quantitative prosodic measures, which correlated with gradient variability as well as digit span test scores. Overall, these findings confirm that long before the clinical stage and objective cognitive impairment, increased risk of cognitive decline as indexed by Aβ accumulation is marked by neurofunctional changes in the cortical hierarchy, which are related to automatically extractable speech patterns and alterations in working memory functions.

中文翻译：

---

Aβ阳性老年人的非典型皮质层次结构及其在自发言语中的反映

Aβ 淀粉样蛋白的异常沉积是阿尔茨海默病 (AD) 的早期神经病理学标志，其出现早于临床症状。相关早期神经功能变化的非侵入性测量，以及这些变化的易于获取的行为读数，可能具有巨大的临床益处。我们通过使用功能 MRI 研究功能连接的大规模皮层梯度来实现这一目标，该梯度捕获了认知未受损的老年人（无论有或没有 Aβ 阳性（总 N = 188）。我们预测 Aβ+ 组中皮质层次结构的扭曲与韵律变化相关。结果证实，Aβ + 组的皮质层次结构发生了显着改变，其变异性较小，并且定量韵律测量有所增加，这与梯度变异性以及数字跨度测试分数相关。总体而言，这些发现证实，早在临床阶段和客观认知障碍之前，以 Aβ 积累为指标的认知能力下降风险增加的特点是皮质层次结构中的神经功能变化，这与自动提取的语音模式和工作记忆功能的改变有关。