Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
(2023) In Human Brain Mapping 44(7). p.2684-2700- Abstract
Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic... (More)
Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- frontotemporal dementia, genetics, magnetic resonance imaging, neuropsychiatry
- in
- Human Brain Mapping
- volume
- 44
- issue
- 7
- pages
- 17 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85150648466
- pmid:36895129
- ISSN
- 1065-9471
- DOI
- 10.1002/hbm.26220
- language
- English
- LU publication?
- yes
- id
- ebb2c43d-03ba-4909-b15b-042eed59cf67
- date added to LUP
- 2023-05-29 13:26:39
- date last changed
- 2024-06-15 03:30:57
@article{ebb2c43d-03ba-4909-b15b-042eed59cf67,
abstract = {{<p>Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.</p>}},
author = {{Bussy, Aurélie and Levy, Jake P. and Best, Tristin and Patel, Raihaan and Cupo, Lani and Van Langenhove, Tim and Nielsen, Jørgen E. and Pijnenburg, Yolande and Waldö, Maria Landqvist and Remes, Anne M. and Schroeter, Matthias L. and Santana, Isabel and Pasquier, Florence and Otto, Markus and Danek, Adrian and Levin, Johannes and Le Ber, Isabelle and Vandenberghe, Rik and Synofzik, Matthis and Moreno, Fermin and de Mendonça, Alexandre and Sanchez-Valle, Raquel and Laforce, Robert and Langheinrich, Tobias and Gerhard, Alexander and Graff, Caroline and Butler, Chris R. and Sorbi, Sandro and Jiskoot, Lize and Seelaar, Harro and van Swieten, John C. and Finger, Elizabeth and Tartaglia, Maria Carmela and Masellis, Mario and Tiraboschi, Pietro and Galimberti, Daniela and Borroni, Barbara and Rowe, James B. and Bocchetta, Martina and Rohrer, Jonathan D. and Devenyi, Gabriel A. and Chakravarty, M. Mallar and Ducharme, Simon}},
issn = {{1065-9471}},
keywords = {{frontotemporal dementia; genetics; magnetic resonance imaging; neuropsychiatry}},
language = {{eng}},
number = {{7}},
pages = {{2684--2700}},
publisher = {{Wiley-Blackwell}},
series = {{Human Brain Mapping}},
title = {{Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia}},
url = {{http://dx.doi.org/10.1002/hbm.26220}},
doi = {{10.1002/hbm.26220}},
volume = {{44}},
year = {{2023}},
}