Cerebellar White Matter Disruption in Alzheimer’s Disease Patients: A Diffusion Tensor Imaging Study

Toniolo, Sofia; Serra, Laura; Olivito, Giusy; Caltagirone, Carlo; Mercuri, Nicola Biagio; Marra, Camillo; Cercignani, Mara; Bozzali, Marco

doi:10.3233/jad-191125

Cited by 27 publications

(14 citation statements)

References 66 publications

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“…An increasing number of imaging studies have confirmed that cerebellar Crus II and lobular IX are associated with cognitive networks (32,34,35), particularly with the default mode network (DMN) and fronto-parietal network (FPN) (36)(37)(38). The anterior cerebellum and lobule VIII are associated with movement, whereas the posterior cerebellum (i.e., lobule VI-Crus I, lobule Crus II-VIIB, and lobule IX) are critical for cognitive representation (39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach

Tang

Zhu

et al. 2021

Front. Neurol.

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Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated.Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects.Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance.Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI.Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.

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Section: Introductionmentioning

confidence: 99%

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach

Tang

Zhu

et al. 2021

Front. Neurol.

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“…The mechanism of CCD include the involvement of cortico-pontocerebellar and the cerebello-thalamo-cortical circuits (Dum and Strick, 2003;Di Lorenzo et al, 2013). Using diffuse tension imaging (DTI), Sofia Toniolo et al provide the evidence of the impairment of microstructural fiber integrity of cerebellum WM tracts in AD (Toniolo et al, 2020). However, whether the focal change in the cerebellum is a form of Wallerian degeneration or the result of accumulation of AD pathological substrates in the cerebellum itself is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: A Case-Control Study

Zhou

Zhu

Shao

et al. 2021

Front. Syst. Neurosci.

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This case-control study is aimed to investigate the correlation of altered functional connectivity (FC) in cerebellum with cognitive impairment in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). The morphometric and resting-state FC MRI analysis including 46 participants with AD, 32 with aMCI and 42 age-matched normal controls (NCs) were conducted. We compared the cerebellar gray matter volume and cerebellar FC with cerebral cortical regions among three groups. To investigate the relationship of cerebellar FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain. No significant morphometric differences of cerebellum was observed across three groups. The patients with AD had weaker cerebral cortical FCs in bilateral Crus I and left VIIb compared to NCs, and in bilateral Crus I compared to patients with aMCI. For patients with aMCI, the weaker FC were found between right Crus I, left VIIb and cerebral cortical regions compared to NCs. The strength of left cerebellar FC positively correlated with specific cognitive subdomains, including memory, executive function, visuospatial function, and global cognition in AD and aMCI. These findings demonstrated the alteration of cerebellar FC with cerebral cortical regions, and the correlation of cerebellar FC and cognitive impairment in AD and aMCI.

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“…Disease-specific clusters of cerebellar atrophy have been found in Alzheimer’s disease, Frontotemporal Dementia and Amyotrophic lateral sclerosis 78 . Functional connectivity alterations 22,23 and white matter disruption 79 characterize cerebro-cerebellar loops in Alzheimer’s disease patients. Abnormal network connectivity between cerebellum and cerebral cortical regions has been confirmed in the main subtypes of Frontotemporal Dementia 80,81 (behavioral-variant, semantic dementia and progressive nonfluent aphasia).…”

Section: Discussionmentioning

confidence: 99%

Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases

Monteverdi¹,

Palesi

Costa

et al. 2021

Preprint

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Brain pathologies are based on microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients excitation/inhibition profiles on neurodegenerative diseases including Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. In this work we used a simulation platform, The Virtual Brain, to simulate brain dynamics in healthy controls and in Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis patients. The brain connectome and functional connectivity were extracted from 3T-MRI scans and The Virtual Brain nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the excitatory/inhibitory balance. The integration of cerebro-cerebellar loops improved the correlation between experimental and simulated functional connectivity, and hence The Virtual Brain predictive power, in all pathological conditions. The Virtual Brain biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in Alzheimer's disease and stronger NMDA (N-methyl-D-aspartate) receptor-dependent excitation in Amyotrophic Lateral Sclerosis. These physio-pathological parameters allowed an advanced analysis of patients' state. In backward regressions, The Virtual Brain parameters significantly contributed to explain the variation of neuropsychological scores and, in discriminant analysis, the combination of The Virtual Brain parameters and neuropsychological scores significantly improved discriminative power between clinical conditions. Eventually, cluster analysis provided a unique description of the excitatory/inhibitory balance in individual patients. In aggregate, The Virtual Brain simulations reveal differences in the excitatory/inhibitory balance of individual patients that, combined with cognitive assessment, can promote the personalized diagnosis and therapy of neurodegenerative diseases.

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Cerebellar White Matter Disruption in Alzheimer’s Disease Patients: A Diffusion Tensor Imaging Study

Cited by 27 publications

References 66 publications

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach

Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: A Case-Control Study

Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases

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