Multimodal MRI of grey matter, white matter, and functional connectivity in cognitively healthy mutation carriers at risk for frontotemporal dementia and Alzheimer's disease.

Autor: Feis RA; Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands. r.a.feis@lumc.nl.; FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. r.a.feis@lumc.nl.; LIBC, Leiden Institute for Brain and Cognition, Leiden, The Netherlands. r.a.feis@lumc.nl., Bouts MJRJ; Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.; LIBC, Leiden Institute for Brain and Cognition, Leiden, The Netherlands.; Institute of Psychology, Leiden University, Leiden, The Netherlands., Dopper EGP; Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands., Filippini N; FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.; Department of Psychiatry, University of Oxford, Oxford, UK., Heise V; FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.; Department of Psychiatry, University of Oxford, Oxford, UK., Trachtenberg AJ; FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., van Swieten JC; Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands., van Buchem MA; Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.; LIBC, Leiden Institute for Brain and Cognition, Leiden, The Netherlands., van der Grond J; Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands., Mackay CE; FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.; Department of Psychiatry, University of Oxford, Oxford, UK., Rombouts SARB; Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.; LIBC, Leiden Institute for Brain and Cognition, Leiden, The Netherlands.; Institute of Psychology, Leiden University, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: BMC neurology [BMC Neurol] 2019 Dec 27; Vol. 19 (1), pp. 343. Date of Electronic Publication: 2019 Dec 27.
DOI: 10.1186/s12883-019-1567-0
Abstrakt: Background: Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk.
Methods: We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation).
Results: MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses.
Conclusions: Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD.
Databáze: MEDLINE
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