Unstable functional brain states and reduced cerebro-cerebellar modularity in elderly individuals with subjective cognitive decline

The preclinical stage of Alzheimer's Disease (AD) holds great potential for intervention, therefore, it is crucial to elucidate the neural mechanisms underlying the progression of subjective cognitive decline (SCD). Previous studies have predominantly focused on the neural changes in the cerebrum associated with SCD, but have relatively neglected the cerebellum, and its functional relationship with the cerebrum. In the current study, we employed dynamic functional connectivity and large-scale brain network approaches to investigate the pathological characteristics of dynamic brain states and cerebro-cerebellar collaboration between SCD (n = 32) and the healthy elderly (n = 29) using resting-state fMRI. Two-way repeated measures ANOVA and permutation t-tests revealed significant group differences, with individuals with SCD exhibiting shorter state duration and more frequent transitions between states compared to the healthy elderly individuals. Additionally, individuals with SCD showed lower levels of intracerebellar functional connectivity, but higher levels of cerebellar-cerebral functional integration. Furthermore, the hub nodes of the functional networks in SCD shifted between the cerebellum and cerebrum across different brain states. These findings indicate that SCD exhibits greater state instability but may compensate for the negative effects of early disease by integrating cerebellar and cerebral networks, thereby maintaining cognitive performance. This study enhances our theoretical understanding of cerebellar-cerebral relationship changes in the early stages of AD and provides evidence for early interventions targeting the cerebellum.