Cerebellar‐cortical functional connectivity is associated with Alzheimer’s disease pathology and cerebellar atrophy

Abstract

AbstractBackgroundBrain atrophy has been associated with Alzheimer’s disease (AD) pathology. Previous research also suggests that functional connectivity (FC) among distributed neural networks is disrupted in preclinical AD. The cerebellum has been thought to play a crucial role in motor control, yet recent evidence points to its additional role in non‐motor domains as well as cognitive decline in AD. Cerebellar volume has been shown to decline along the course of AD progression. Moreover, neuroimaging studies have delineated intrinsic cerebellar‐cortical functional networks that presumably support cognitive functions. Despite the accumulating findings on neurodegeneration or FC, how cerebellar FC and atrophy relate to AD pathology in the early stage has not been extensively investigated.MethodData from 83 cognitively normal older adults (mean 71.0 yrs, 66% females) in the Alzheimer’s Disease Neuroimaging Initiative were analyzed. Volumetric data were obtained from FreeSurfer 6.0 segmentation. Resting state fMRI scans were preprocessed using the CONN Toolbox. Aβ and tau standardized uptake value ratio (SUVR) data were obtained from [18F]‐Florbetapir or [18F]‐Florbetaben (Aβ) and [18F]‐Flortaucipir (tau) PET scans. For Aβ, SUVR values were transformed to the Centiloid scale, and a global summary measure was used. For tau, SUVR values in the temporal meta regions of interest were used. Seed‐based functional connectivity metrics were computed using the 7 cerebellar parcellations (Buckner et al., 2011) that are functionally coupled to different cortical networks (Yeo et al., 2011).ResultCerebellar volume showed no significant relationship with amyloid or tau SUVR. By contrast, hippocampal atrophy was positively associated with amyloid or tau SUVR and showed trending significance (ps < 0.1). Increased Aβ burden was associated with increased cerebellar‐cortical FC in the attention, frontoparietal, and default mode networks. Increased tau load was associated with increased cerebellar‐cortical FC in the visual, somatomotor, and attention networks. Cerebellar volume was associated with cerebellar‐cortical FC in the visual, somatomotor, attention networks, but not with the limbic, frontoparietal, or default mode networks.ConclusionOur findings suggest that functional cerebellar‐cortical connectivity varies with amyloid and tau pathology in different networks, and such functional changes may precede cerebellar atrophy in preclinical AD.