The cerebellum in frontotemporal dementia: From neglected bystander to potential neuromodulatory target. A narrative review
Annibale Antonioni, Emanuela Maria Raho, Danny Spampinato, Enrico Granieri, Luciano Fadiga, Francesco Di Lorenzo, Giacomo Koch
Abstract
BACKGROUND: Though cortical changes in frontotemporal dementia (FTD) are well-documented, the cerebellum's role, closely linked to these areas, remains unclear. OBJECTIVES: To provide evidence on cerebellar involvement in FTD across clinical, genetic, imaging, neuropathological, and neurophysiological perspectives. Additionally, we sought evidence supporting the application of cerebellar non-invasive brain stimulation (NIBS) in FTD for both diagnostic and therapeutic purposes. METHODS: We performed a literature review using MEDLINE (via PubMed), Scopus, and Web of Science databases. RESULTS: We emphasized the involvement of specific cerebellar regions which differentiate each FTD subtypes and may account for some of the characteristic symptoms. Furthermore, we highlighted peculiarities in FTD genetic alterations. Finally, we outlined neurophysiological evidence supporting a role for the cerebellum in FTD pathogenesis. CONCLUSION: The cerebellum is critically involved in the FTD spectrum. Moreover, it can be speculated that cerebellar modulation, as already shown in other neurodegenerative disorders, could restore the interneuronal intracortical circuits typically impaired in FTD patients, providing clinical improvements and fundamental outcome measures in clinical trials.