Exploring dynamic functional connectivity alterations in the preclinical stage of Alzheimer’s disease: an exploratory study from SICOLDE

Abstract IntroductionExploring functional connectivity (FC) alterations is important for the understanding of underlying neuronal network alterations in subjective cognitive decline (SCD). The objective of this study was to discover stable and subtle dynamic functional connectivity (FC) changes in the preclinical stage of Alzheimer’s disease (AD), and to explore the associations between dynamic FCs and amyloid accumulation.MethodsNinety-seven normal control (NC) subjects, 101 subjective cognitive decline (SCD) subjects, and 55 cognitive impairment (CI) subjects with neuropsychological assessments and resting-state functional magnetic resonance images constituted the whole cohort. Of these, 29 NCs and 52 SCDs with amyloid images were selected as the sub-cohort. First, independent components (ICs) identified by group independent component analysis (ICA) were used to define static and dynamic brain networks. Static and sliding-window dynamic FCs were then calculated. Second, the connection between each pair of ICs was compared between groups in the two cohorts. Hubs were obtained and considered as seeds in the subsequent seed-based dynamic FC analysis. One-way analysis of variance (ANOVA) was used to compare the seed-based dynamic FC maps between groups in the whole cohort, while a 2×2 ANOVA model was used to measure the group or amyloid effects in the sub-cohort. Post-hoc analysis was applied, and differences were considered significant if the cluster-level FWE-corrected p-value was less than 0.001. Finally, correlation analysis was conducted between the altered dynamic FCs, neuropsychological assessments, and amyloid burden.ResultsThe results showed that 42 ICs were revealed. Compared with the static FCs, the dynamic FCs were found to be more stable and sensitive between groups. The effective dynamic FCs included those between the salience/ventral attention network, the default mode network, and the visual network. Specifically, the dynamic FC of the thalamus/caudate (IC 25) drove the hub role in the group differences between the NC and SCD groups. In the seed-based dynamic FC analysis, the dynamic FC between the thalamus/caudate and the middle temporal/frontal gyrus was observed to be higher in the SCD and CI groups in the whole cohort. Moreover, a higher dynamic FC between the thalamus/caudate and visual cortex was observed in the amyloid positive group. Finally, the altered dynamic FC was associated with the amyloid global level standardized uptake value ratio.ConclusionOur findings indicate that dynamic FCs can reflect subtle changes in the preclinical stage of AD.