Patterns of Cerebellar Gray Matter Atrophy Across Alzheimer’s Disease Progression

Abstract

The role of the cerebellum in cognitive function has been broadly investigated in the last decades from an anatomical, clinical, and functional point of view and new evidence points toward a significant contribution of the posterior lobes of the cerebellum in cognition in Alzheimer’s disease (AD). In the present work we used SUIT-VBM (spatially unbiased infratentorial template, voxel-based morphometry) to perform an analysis of the pattern of cerebellar gray matter (GM) atrophy in amnestic mild cognitive impairment (a-MCI) and AD dementia patients compared to healthy subjects (HS), in order to follow the changes of non-motor features of cerebellar degeneration throughout disease progression. This template has been validated to guarantee a significant improvement in voxel-to-voxel alignment of the individual fissures and the deep cerebellar nuclei compared to Montreal Neurological Institute (MNI) whole-brain template. Our analysis shows a progression of cerebellar GM volume changes throughout a continuous spectrum from early to late clinical stages of AD. In particular vermis and paravermian areas of the anterior (I-V) and posterior (VI) lobes are involved since the a-MCI stage, with a later involvement of the hemispheric part of the posterior lobes (VI lobule) and Crus I in AD dementia patients only. These findings support the role of the cerebellum in higher-level functions, and whilst confirming previous data on the involvement of Crus I in AD dementia, provide new evidence of an involvement of the vermis in the early stages of the disease.

A Novel Connectome-based Electrophysiological Study of Subjective Cognitive Decline Related to Alzheimer’s Disease by Using Resting-state High-density EEG EGI GES 300

“…Additionally, differences were observed among groups in the case of the cerebellum, where lower activation was detected in later stages of the disease. In line with our results, recent studies have highlighted the role of cerebellum in the AD hypothesis and its pivotal role in cognitive impairment [129,130]. Our findings support and underline the importance of a reasonable and consistent interchange among particular brain areas and support that interruption or any disconnection in these specific regions may be linked to the future development of AD.…”

Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment

“…In line with previous literature our results do not show a significant difference in cerebellar volume between healthy individuals and aMCI patients [71,72]. Recent work suggested that the Crus I would show atrophy late in the disease process [73] leaving us to speculate that functional connectivity changes of the cerebellar-cerebral DMN precede atrophy of the cerebellar DMN region. Since the association with memory was only observed for the frontal region and not the medial temporal regions and no association was shown with executive functioning, we propose-in keeping with the dysmetria of thought hypothesis [74,75]-that the cerebellum has a modulating role on the executive components of memory performance.…”

Unsuspected Involvement of Spinal Cord in Alzheimer Disease

“…It is indeed very significant that a recent study of another animal model of AD (the 5xFAD) shows amyloid plaques accumulation in the spinal cord tissue, with a particular concentration at cervical level and a time-dependent accumulation that starts 11 weeks from onset; interestingly, the same study found independent and extensive myelopathy, while the motoneurons count at 6 months was not altered compared to the wild type (Chu et al, 2017). While, we cannot be conclusive on the mechanisms of spinal cord atrophy in AD, our results are intriguing and calling for larger studies of prodromic subjects to be followed over time; such studies would also confirm whether the suggestion that the motor system (neocortex, cerebellum and spinal cord) is affected even before the cognitive one can be substantiated, or whether the spinal cord is following similar pathophysiological global changes as brain structures (Agosta et al, 2010;Albers et al, 2015;Toniolo et al, 2018). A further result of our work is that of all spinal cord features analyzed here, the area of vertebra C2-C3 (CSA23) significantly contributes to discrimination between HC and AD patients.…”

“…Optical Coherence Tomography studies, for example, have been used to demonstrate that retinal ganglion cell degeneration can be associated with early stages of AD. Also, structures like the cerebellum, not classically associated with AD, have been found to be altered in imaging studies of dementia (Castellazzi et al, 2014), with atrophy of the anterior cerebellum-known for its motor control-being present even in the prodromic stages of mild cognitive impairment (MCI; Toniolo et al, 2018). Recent work has also looked at graph theory metrics to distinguish patterns of AD, identifying potentially different subtypes (Ferreira et al, 2019), although focusing on cortical and deep gray matter areas, without including the cerebellum and the spinal cord.…”