DEMENTIA in Cerebellar Volume in Genetic FTD

RESEARCH HIGHLIGHTS

Nature Reviews Neurology | Published online 11 Mar 2016; doi:10.1038/nrneurol.2016.28

DEMENTIA in cerebellar volume in genetic FTD. “We decided to investigate the volume of cerebellar subregions to Cerebellar atrophy has determine whether specific areas are associated with mutations in the key FTD genes,” explains Rohrer. disease-specific patterns Using MRI, the team determined the volumes of cerebellar subregions Distinct patterns of cerebellar question that remained was whether in 44 patients with mutations in atrophy relate to wider patterns of cerebellar changes were associated C9orf72, MAPT or GRN. GRN Patterns of disease-specific brain network degen- with cortical changes, or just occurred mutations were not associated with cerebellar eration, according to two recent concomitantly,” says Hornberger. cerebellar atrophy, whereas C9orf72 atrophy studies. The findings reveal details The team used MRI to visu- mutations were specifically associated of cerebellar atrophy in Alzheimer alize cerebellar degeneration in with atrophy in lobule VIIa–Crus I, differed disease (AD) and frontotemporal 217 patients with AD or one of and MAPT mutations were specif- between AD dementia (FTD), with implications three FTD subtypes: behavioural ically associated with atrophy in and bvFTD for future research and therapy. variant FTD, nonfluent variant pri- the vermis. Cerebellar degeneration has mary progressive aphasia (nfvPPA), “C9orf72‑associated atrophy largely been disregarded in demen- and semantic variant PPA (svPPA). reflects degeneration of a cortico- tia owing to its association with They then compared the atrophy thalamo-cerebellar network impor- movement disorders. However, the maps with an atlas of cerebral and tant in cognition, and the vermis cerebellum is involved in cognition cerebellar connectivity. is involved in emotion processing,” and emotion, and evidence indi- Patterns of cerebellar atrophy explains Rohrer. cates that cerebellar changes are differed between AD and bvFTD, Both teams now intend to further important in a range of neurological and the areas that degenerated had investigate the implications of disorders. The two new studies, one connections to cortical networks that their findings. “The next question led by Michael Hornberger and the exhibit disease-specific degeneration. is whether cerebellar or cerebral other by Jonathan Rohrer, add to In AD, atrophy occurred in the changes occur first,” says Hornberger. this evidence. Crus I and II subregions, part of the He also points out that the cerebellum Hornberger and colleagues con- default mode network. In bvFTD, is often used as a reference area in tinued from their previous character- atrophy occurred in lobule VI of PET studies of neurodegeneration, ization of cerebellar atrophy in AD, the cerebellum, part of the salience and that these findings cast doubt on FTD and motor neuron disease. “The network. “In our view, this is the this approach. first evidence that discrete cortical Rohrer and colleagues hope to changes are linked to cerebellar learn more about the clinical poten- atrophy,” says Hornberger. tial of their findings. “Identification Differences in cerebellar atrophy of particular network involvement in between FTD subtypes were less FTD could help to identify specific clear, although the patterns seemed targets for therapies,” he concludes. to be distinct, suggesting subtype- Ian Fyfe specific degeneration. The findings of Rohrer and colleagues, who focused ORIGINAL ARTICLES Guo, C. G. et al. Network- on cerebellar atrophy in genetic selective vulnerability of the human cerebellum to subtypes of FTD, lend weight to Alzheimer’s disease and frontotemporal dementia. Brain http://dx.doi.org/10.1093/brain/aww003 | this hypothesis. Bocchetta, M. et al. Patterns of regional cerebellar Mutations in C9orf72 were associated with atrophy Rohrer and co-workers expanded atrophy in genetic frontotemporal dementia. in lobule VIIa–Crus I (arrow) of the cerebellum, Nature Reviews | Neurology on their previous demonstrations Neuroimage Clin. http://dx.doi.org/10.1016/ which is involved in cognition. Image courtesy j.nicl.2016.02.008 of J. Rohrer. of global presymptomatic changes