Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: A randomized clinical trial.

INTRODUCTION: Evidence indicates that the cerebellum is involved in cognitive processing. However, the specific mechanisms through which the cerebellum repetitive transcranial magnetic stimulation (rTMS) contributes to the cognitive state are unclear. METHODS: In the current randomized, double-blind, sham-controlled trial, 27 patients with Alzheimer's disease (AD) were randomly allotted to one of the two groups: rTMS-real or rTMS-sham. We investigated the efficacy of a four-week treatment of bilateral cerebellum rTMS to promote cognitive recovery and alter specific cerebello-cerebral functional connectivity. RESULTS: The cerebellum rTMS significantly improves multi-domain cognitive functions, directly associated with the observed intrinsic functional connectivity between the cerebellum nodes and the dorsolateral prefrontal cortex (DLPFC), medial frontal cortex, and the cingulate cortex in the real rTMS group. In contrast, the sham stimulation showed no significant impact on the clinical improvements and the cerebello-cerebral connectivity. CONCLUSION: Our results depict that 5 Hz rTMS of the bilateral cerebellum is a promising, non-invasive treatment of cognitive dysfunction in AD patients. This cognitive improvement is accompanied by brain connectivity modulation and is consistent with the pathophysiological brain disconnection model in AD patients.

Neuroimaging alterations in dementia with Lewy bodies and neuroimaging differences between dementia with Lewy bodies and Alzheimer's disease: An activation likelihood estimation meta-analysis.

AIMS: The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described. METHODS: PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate-based meta-analysis and functional meta-analytic connectivity modeling were performed using the activation likelihood estimation algorithm. RESULTS: Eleven structural studies and fourteen functional studies were included in this quantitative meta-analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal-parietal, salience, and visual networks were all abnormally co-activated in DLB, but the default mode network remained normally co-activated compared with AD. CONCLUSIONS: The convergence of local brain regions and co-activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD.

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

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.