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Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia
Open accessAbstract
Objective: We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of MAPT (microtubule-associated protein tau) or GRN (progranulin) mutations. Methods: In this case-control study, 75 healthy individuals (aged 20–70 years) with 50% risk of frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, structural MRI, and fMRI. We used voxel-based morphometry and tract-based spatial statistics for voxel-wise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsular, anterior midcingulate, and posterior cingulate cortices. Results: Carriers (n = 39) and noncarriers (n = 36) had similar neuropsychological performance, except for lower Letter Digit Substitution Test scores in carriers. Worse performance on Stroop III, Rivermead Behavioral Memory Test, and Happé Cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy in the right uncinate fasciculus was found in carriers compared with controls. Reductions in functional connectivity between anterior midcingulate cortex and frontoinsula and several other brain regions were found in carriers compared with controls and correlated with higher age in carriers, but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found, except for a small cluster of higher volume in the precentral gyrus in carriers. Conclusions: This study demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.
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“In line with previous studies, the functional ROI-to-ROI models showed alterations in fronto-temporal (Jastorff et al., 2016; Meijboom et al., 2017), intrafrontal (Dopper et al., 2014; Whitwell, 2019), and precuneus-insula (Whitwell et al., 2011b) connectivity.”
From Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference (2023) · cites this paper as Dopper et al., 2014
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“while brain connectivity alterations may be present at early stages (Dopper et al., 2014; Meeter et al., 2017).”
From Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference (2023) · cites this paper as Dopper et al., 2014
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Metadata
- Authors
- Dopper, E. G. P., Rombouts, S. A. R. B., Jiskoot, L. C., den Heijer, T., de Graaf, J. R. A., de Koning, I., Hammerschlag, A. R., Seelaar, H., Seeley, W. W., Veer, I. M., van Buchem, M. A., Rizzu, P., & van Swieten, J. C.
- Affiliations
- Leiden University (NL)
- From the Departments of Neurology (E.G.P.D., L.C.J., T.d.H., H.S., J.C.v.S.), Epidemiology (T.d.H.), and Neuropsychology (J.R.A.d.G., I.d.K.), Erasmus Medical Center, Rotterdam; Department of Radiology (E.G.P.D., S.A.R.B.R., I.M.V., M.A.v.B.), Leiden University Medical Center; Departments of Neurology (E.G.P.D.) and Clinical Genetics (A.R.H., P.R., J.C.v.S.), VU Medical Center, Amsterdam; Leiden Institute for Brain and Cognition (S.A.R.B.R., I.M.V., M.A.v.B.) and Institute of Psychology (S.A.R.B.R.,...
- ORCID
- Venue
- Neurology
- Published
- 2014-07-08
- Volume
- 83
- Issue
- 2
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W4251162813
- Cited by
- 152
- References
- 35
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 5 · 2023: 13 · 2022: 12 · 2021: 11 · 2020: 13 · 2019: 19 · 2018: 12 · 2017: 11 · 2016: 14 · 2015: 11 · 2014: 6
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Neurology (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- frontotemporal dementia, presymptomatic carriers, MAPT mutations, GRN mutations, familial frontotemporal dementia, brain connectivity, functional connectivity, structural connectivity, uncinate fasciculus, fractional anisotropy, anterior midcingulate cortex, frontoinsular cortex, posterior cingulate cortex, gray matter volume, cognitive impairment, early biomarkers, diffusion tensor imaging, resting-state fMRI
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