Patterns of Cerebellar Gray Matter Atrophy Across Alzheimer's Disease Progression.

Sofia Toniolo,Laura Serra,Mara Cercignani,Giusy Olivito,Marco Bozzali,Camillo Marra

doi:10.3389/fncel.2018.00430

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.

Highlights

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide, leading to a progressive loss of cognitive and functional abilities
One hundred forty nine participants were recruited from the Dementia unit of the Catholic University, Rome: 53 patients with probable AD dementia according to the new McKhann criteria of 2011 (McKhann et al, 2011), 62 amnestic mild cognitive impairment (MCI) (a-MCI) patients according to Albert Criteria of 2011 (Albert et al, 2011) and Petersen Criteria of 2014 (Petersen et al, 2014), and 34 healthy subjects (HS)
AD dementia patients showed a statistically lower mini-mental state examination (MMSE) compared to amnestic mild cognitive impairment (a-MCI) and HS patients, as well as lower scores in Rey 15 list immediate and delayed recall, Phonological verbal fluency, Digit span forward and back, Corsi blocking task forward, Copy of drawings and Copy of drawings with landmarks and Raven’s progressive matrices

Summary

Introduction

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide, leading to a progressive loss of cognitive and functional abilities. 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 (Leggio and Olivito, 2018) since the original description of the CCAS by Schmahmann and Sherman (1998). This syndrome was originally described as a subset of symptoms due to the selective damage to the vermis and posterior lobe of the cerebellum. Deficits in executive functions, attentional processes, working memory and divided attention have been described after microsurgical treatment of tumors or hematomas in the cerebellum (Gottwald et al, 2004; De Ribaupierre et al, 2008; Grossauer et al, 2015)

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