Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study
Open accessAbstract
Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease.
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Genetic bvFTD patients tend to have more atypical atrophy patterns.
“Of note, our algorithm was able to accurately classify patients with genetic bvFTD even though they tend to have more atypical atrophy patterns. 21”
From MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia (2021) · cites this paper as [21]
The Discussion (page unavailable) reports distinct atrophy patterns across genetic FTD mutation groups, including widespread and posterior atrophy in C9orf72 carriers. But the paper does not establish that genetic bvFTD patients tend to have more atypical patterns than other bvFTD patients; its atrophy analysis is not limited to bvFTD or compared with sporadic bvFTD. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAtrophy patterns can give cues towards genetic aetiology, such as the involvement of the parietal cortex, asymmetric hemispheric atrophy and white matter hyperintensities with GRN mutations.
“Atrophy patterns can further give cues towards genetic aetiology, such as the involvement of the parietal cortex, asymmetric hemispheric atrophy and white matter hyperintensities with GRN mutations (Cash et al. , 2018).”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Cash et al. , 2018
The Results (Symptomatic mutation carriers) and Discussion report parietal atrophy in GRN mutation carriers, and the Discussion notes that their atrophy can be asymmetric between hemispheres. The paper examines gray-matter atrophy; the passages found do not report white matter hyperintensities with GRN mutations, so that part of the cited claim is unsupported. (LLM, conf=0.88)
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- Authors
- Cash, D. M., Bocchetta, M., Thomas, D. L., Dick, K. M., van Swieten, J. C., Borroni, B., Galimberti, D., Masellis, M., Tartaglia, M. C., Rowe, J. B., Graff, C., Tagliavini, F., Frisoni, G. B., Laforce, R., Finger, E., de Mendonça, A., Sorbi, S., Rossor, M. N., Ourselin, S., Rohrer, J. D., Andersson, C., Archetti, S., Arighi, A., Benussi, L., Black, S., Cosseddu, M., Fallström, M., Ferreira, C., Fenoglio, C., Fox, N., Freedman, M., Fumagalli, G., Gazzina, S., Ghidoni, R., Grisoli, M., Jelic, V., Jiskoot, L., Keren, R., Lombardi, G., Maruta, C., Mead, S., Meeter, L., van Minkelen, R., Nacmias, B., Öijerstedt, L., Padovani, A., Panman, J., Pievani, M., Polito, C., Premi, E., Prioni, S., Rademakers, R., Redaelli, V., Rogaeva, E., Rossi, G., Rossor, M., Scarpini, E., Tang-Wai, D., Tartaglia, C., Thonberg, H., Tiraboschi, P., Verdelho, A., & Warren, J.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- University of Brescia (IT)
- University of Milan (IT)
- Sunnybrook Health Science Centre (CA)
- University of Cambridge (GB)
- Karolinska University Hospital (SE)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- Université Laval (CA)
- Western University (CA)
- University of Florence (IT)
- Corresponding author
- Rohrer, Jonathan D.
- ORCID
- Cash, David M.
- Bocchetta, Martina
- Thomas, David L.
- Borroni, Barbara
- Galimberti, Daniela
- Masellis, Mario
- Rowe, James B.
- Graff, Caroline
- Tagliavini, Fabrizio
- Frisoni, Giovanni B.
- Laforce, Robert
- Finger, Elizabeth
- Sorbi, Sandro
- Rohrer, Jonathan D.
- Arighi, Andrea
- Benussi, Luisa
- Black, Sandra
- Cosseddu, Maura
- Ferreira, Carlos
- Fenoglio, Chiara
- Fox, Nick
- Freedman, Morris
- Fumagalli, Giorgio
- Gazzina, Stefano
- Ghidoni, Roberta
- Grisoli, Marina
- Jiskoot, Lize
- Keren, Ron
- Lombardi, Gemma
- Maruta, Carolina
- Mead, Simon
- Meeter, Lieke
- Nacmias, Benedetta
- Öijerstedt, Linn
- Padovani, Alessandro
- Panman, Jessica
- Pievani, Michela
- Polito, Cristina
- Premi, Enrico
- Prioni, Sara
- Rademakers, Rosa
- Redaelli, Veronica
- Rogaeva, Ekaterina
- Rossi, Giacomina
- Scarpini, Elio
- Tiraboschi, Pietro
- Verdelho, Ana
- Warren, Jason
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 62
- Pages
- 191-196
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC5759893
- OpenAlex
- W2766970894
- Cited by
- 200
- References
- 1
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 11 · 2023: 16 · 2022: 34 · 2021: 29 · 2020: 31 · 2019: 27 · 2018: 13 · 2017: 1
- FWCI
- 16.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by-nc-nd)
- RePub (Erasmus University Rotterdam) (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Florence Research (University of Florence) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Apollo (cc-by)
- Funders
- Wellcome Trust (103838/Z/14/Z, 103838)
- Alzheimer's Society
- National Institute for Health and Care Research (NF-SI-0512-10033, NF-SI-0617-10175, 103838, CL-2012-18-010)
- Brain Research Trust
- Wolfson Foundation
- Cambridge University Hospitals (146281)
- Ministero della Salute
- Canadian Institutes of Health Research
- Medical Research Council (MR/M023664/1, MR/M024873/1, MR/M009106/1, MR/M008525/1, MR/J009482/1, MR/M009041/1)
- NIHR Cambridge Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- frontotemporal dementia, gray matter atrophy, C9orf72, gene regulatory networks, MAPT, presymptomatic mutation carriers, anterior insula, anterior cingulate cortex, thalamus, cerebellum, temporal lobe, striatum, voxel-based morphometry
- MeSH terms
- C9orf72 Protein, Progranulins, Adult, Aged, Atrophy, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Organ Size, Cohort Studies, tau Proteins, Intercellular Signaling Peptides and Proteins, Frontotemporal Dementia, Gray Matter
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