Abstract
Recent findings challenge the prior notion that the cerebellum remains unaffected by Alzheimer’s disease (AD). Yet, it is unclear whether AD exacerbates age-related cerebellar grey matter decline or engages distinct structural and functional territories. We performed a meta-analysis of cerebellar grey matter loss in normal ageing and AD. We mapped voxels with structural decline onto established brain networks, functional parcellations, and along gradients that govern the functional organisation of the cerebellum. Importantly, these gradients track continuous changes in cerebellar specialisation providing a more nuanced measure of the functional profile of regions vulnerable to ageing and AD. Gradient 1 progresses from motor to cognitive territories; Gradient 2 isolates attentional processing; Gradient 3 captures lateralisation differences in cognitive functions. We identified bilateral and right-lateralised posterior cerebellar atrophy in ageing and AD, respectively. Age- and AD-related structural decline only showed partial spatial overlap in right lobule VI/Crus I. Despite the seemingly distinct patterns of AD- and age-related atrophy, the functional profiles of these regions were similar. Both participate in the same macroscale networks (default mode, frontoparietal, attention), support executive functions and language processing, and did not exhibit a difference in relative positions along Gradients 1 or 2. However, Gradient 3 values were significantly different in ageing vs. AD, suggesting that the roles of left and right atrophied cerebellar regions exhibit subtle functional differences despite their membership in similar macroscale networks. These findings provide an unprecedented characterisation of structural and functional differences and similarities in cerebellar grey matter loss between normal ageing and AD.
Highlights
Cerebellar grey matter loss does occur in Alz heimer’s disease (AD), but the healthy ageing process is associated with changes in cerebellar structure, which are comparable in magnitude to those observed in the prefrontal cortex and hippocampus (Bernard and Seid ler, 2014; Jernigan et al, 2001; Raz and Rodrigue, 2006)
We used three complimentary mappings of the cerebellum to char acterise the functional profile of the regions with grey matter loss in ageing and AD: the known intrinsic brain networks based on resting state fMRI (Buckner et al, 2011), the task-based mapping with discrete functional boundaries (King et al, 2019), and a multi-dimensional continuous map reflecting the three major gradients that govern the functional organisation of the cerebellum
Regions with vulnerability to AD and ageing exhibited similar functional profiles: they participated in the same large-scale discrete functional networks, were involved in working memory, attention and language processing, and were located in similar positions along major functional gradients
Summary
Despite the earlier notion that the cerebellum is spared in Alz heimer’s disease (AD), recent studies have started to elucidate detri mental effects of AD on cerebellar structure, which in some cases correlate with clinical disease ratings (Gellersen et al, 2017; Guo et al, 2016a; Jacobs et al, 2018; Serra et al, 2017; Toniolo et al, 2018). Cerebellar grey matter loss does occur in AD, but the healthy ageing process is associated with changes in cerebellar structure, which are comparable in magnitude to those observed in the prefrontal cortex and hippocampus (Bernard and Seid ler, 2014; Jernigan et al, 2001; Raz and Rodrigue, 2006) These marked alterations highlight the importance of the cerebellum for our under standing of both cognitive ageing and Alzheimer’s disease processes. Consistent patterns of AD-related cerebellar atrophy across studies were found in posterior cerebellar lobules (Gellersen et al, 2017), since other authors demonstrated that grey matter loss may occur in anterior lobules of the cerebellum in AD and depends on disease progression (Toniolo et al, 2018)
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