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Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration
Jana Kleinerová, Marlene Tahedl, Mary Clare McKenna, Angela Garcia-Gallardo, Siobhán Hutchinson, Orla M. Hardiman, Cédric Raoul, Fabrice Ango et al.. Journal of Neurology, 2025-03-25
Topic: Brain proteins, microglia and lab models
Radial diffusivity analyses detected impaired bilateral cerebello-frontal, cerebello-parietal, and cerebello-temporal connectivity in all study groups along the ALS-FTD spectrum. Cerebello-occipital disconnection was captured in ALS-FTD and nfvPPA. Spinocerebellar disconnection was detected in C9orf72 negative ALS-FTD and nfvPPA. C9orf72 positive ALS-FTD patients exhibited both anterior and posterior lobe cerebellar volume loss, while bvFTD and nfvPPA patients showed posterior cerebellar atrophy. Flocculonodular degeneration was observed in nfvPPA and cerebellar crura atrophy in bvFTD. Bilateral corticospinal tract and corpus callosum degeneration was detected in ALS-FTD, bvFTD, and nfvPPA. Primary motor cortex volume reductions were captured in both ALS-FTD and nfvPPA. Our analyses capture significant cerebro-cerebellar disconnection in frontotemporal dementia. Corticospinal tract and motor cortex degeneration can be readily detected in non-ALS phenotypes. Intra-cerebellar pathology, coupled with the degeneration of cerebellar projections and the ensuing dysfunction of cerebro-cerebellar networks likely contribute to phenotype-defining clinical profiles in frontotemporal dementia. Infratentorial disease burden and cerebellar network dysfunction should, therefore, be carefully considered in FTD, and phenotype-defining neuropsychological profiles should not be solely attributed to supratentorial degeneration.
Key findings
- Radial diffusivity analyses detected impaired bilateral cerebello-frontal, cerebello-parietal, and cerebello-temporal connectivity in all study groups along the ALS-FTD spectrum.
- Cerebello-occipital disconnection was captured in ALS-FTD and nfvPPA.
- Spinocerebellar disconnection was detected in C9orf72 negative ALS-FTD and nfvPPA.
- C9orf72 positive ALS-FTD patients exhibited both anterior and posterior lobe cerebellar volume loss, while bvFTD and nfvPPA patients showed posterior cerebellar atrophy.
- Flocculonodular degeneration was observed in nfvPPA and cerebellar crura atrophy in bvFTD.
Why it matters
This study found significant cerebro-cerebellar disconnection and intra-cerebellar pathology in frontotemporal dementia, with different patterns across subtypes. It suggests that cerebellar network dysfunction should be considered in FTD, but no treatment or prevention is offered.
Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neurology: journal h-index 208 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Peter Bede: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40131525) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s00415-025-13046-8
- PubMed: 40131525
- Original source →
- Free full text: Journal of Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Kleinerová, J., Tahedl, M., McKenna, M. C., Garcia-Gallardo, A., Hutchinson, S., Hardiman, O. M., et al. (2025). Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration. Journal of Neurology. https://doi.org/10.1007/s00415-025-13046-8
Vancouver
Kleinerová J, Tahedl M, McKenna MC, Garcia-Gallardo A, Hutchinson S, Hardiman OM, et al. Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration. Journal of Neurology. 2025. doi:10.1007/s00415-025-13046-8. PMID: 40131525.
BibTeX
@article{kleinerova2025-40131525,
author = {Kleinerová, Jana and Tahedl, Marlene and McKenna, Mary Clare and Garcia-Gallardo, Angela and Hutchinson, Siobhán and Hardiman, Orla M. and Raoul, Cédric and Ango, Fabrice and others},
title = {{Cerebellar dysfunction in frontotemporal dementia: intra-cerebellar pathology and cerebellar network degeneration}},
journal = {Journal of Neurology},
year = {2025},
doi = {10.1007/s00415-025-13046-8},
pmid = {40131525},
url = {https://doi.org/10.1007/s00415-025-13046-8}
}
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