Atypical cortical hierarchy in A?-positive older adults and its reflection in spontaneous speech

Abnormal deposition of A beta 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 A beta positivity (total N = 188). We predicted distortions of the cortical hierarchy associated with prosodic changes in the A beta + group. Results confirmed substantially altered cortical hierarchies and less variability in these in the A beta + 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 A beta accumulation is marked by neurofunctional changes in the cortical hierarchy, which are related to automatically extractable speech patterns and alterations in working memory functions.