Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers
Introduction: Mutations in the progranulin (GRN) gene are a major source of inherited frontotemporal degeneration (FTD) spectrum disorders associated with TDP-43 proteinopathy. We use structural MRI to identify regions of baseline differences and longitudinal changes in gray matter (GM) and white ma...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158218301633 |
| _version_ | 1819040109404618752 |
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| author | Christopher A. Olm Corey T. McMillan David J. Irwin Vivianna M. Van Deerlin Philip A. Cook James C. Gee Murray Grossman |
| author_facet | Christopher A. Olm Corey T. McMillan David J. Irwin Vivianna M. Van Deerlin Philip A. Cook James C. Gee Murray Grossman |
| author_sort | Christopher A. Olm |
| collection | DOAJ |
| description | Introduction: Mutations in the progranulin (GRN) gene are a major source of inherited frontotemporal degeneration (FTD) spectrum disorders associated with TDP-43 proteinopathy. We use structural MRI to identify regions of baseline differences and longitudinal changes in gray matter (GM) and white matter (WM) in presymptomatic GRN mutation carriers (pGRN+) compared to young controls (yCTL). Methods: Cognitively intact first-degree relatives of symptomatic GRN+ FTD patients with identified GRN mutations (pGRN+; N = 11, mean age = 41.4) and matched yCTL (N = 11, mean age = 53.6) were identified. They completed a MRI session with T1-weighted imaging to assess GM density (GMD) and diffusion-weighted imaging (DWI) to assess fractional anisotropy (FA). Participants completed a follow-up session with T1 and DWI imaging (pGRN+ mean interval 2.20 years; yCTL mean interval 3.27 years). Annualized changes of GMD and FA were also compared. Results: Relative to yCTL, pGRN+ individuals displayed reduced GMD at baseline in bilateral orbitofrontal, insular, and anterior temporal cortices. pGRN+ also showed greater annualized GMD changes than yCTL at follow-up in right orbitofrontal and left occipital cortices. We also observed reduced FA at baseline in bilateral superior longitudinal fasciculus, left corticospinal tract, and frontal corpus callosum in pGRN+ relative to yCTL, and pGRN+ displayed greater annualized longitudinal FA change in right superior longitudinal fasciculus and frontal corpus callosum. Conclusions: Longitudinal MRI provides evidence of progressive GM and WM changes in pGRN+ participants relative to yCTL. Structural MRI illustrates the natural history of presymptomatic GRN carriers, and may provide an endpoint during disease-modifying treatment trials for pGRN+ individuals at risk for FTD. Keywords: Frontotemporal lobar degeneration, Magnetic resonance imaging, Neuroimaging, Progranulin, Presymptomatic, Longitudinal |
| first_indexed | 2024-12-21T09:03:52Z |
| format | Article |
| id | doaj.art-5a4a8ca5b005414e819bbe1cb4ff445a |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-21T09:03:52Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-5a4a8ca5b005414e819bbe1cb4ff445a2022-12-21T19:09:25ZengElsevierNeuroImage: Clinical2213-15822018-01-0119497506Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriersChristopher A. Olm0Corey T. McMillan1David J. Irwin2Vivianna M. Van Deerlin3Philip A. Cook4James C. Gee5Murray Grossman6Penn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States; Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United StatesPenn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United StatesPenn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States; Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United StatesCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPenn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United StatesPenn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United StatesPenn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States; Corresponding author at: Hospital of the University of Pennsylvania, 3400 Spruce Street, 3 West Gates, Philadelphia, PA 19104, United StatesIntroduction: Mutations in the progranulin (GRN) gene are a major source of inherited frontotemporal degeneration (FTD) spectrum disorders associated with TDP-43 proteinopathy. We use structural MRI to identify regions of baseline differences and longitudinal changes in gray matter (GM) and white matter (WM) in presymptomatic GRN mutation carriers (pGRN+) compared to young controls (yCTL). Methods: Cognitively intact first-degree relatives of symptomatic GRN+ FTD patients with identified GRN mutations (pGRN+; N = 11, mean age = 41.4) and matched yCTL (N = 11, mean age = 53.6) were identified. They completed a MRI session with T1-weighted imaging to assess GM density (GMD) and diffusion-weighted imaging (DWI) to assess fractional anisotropy (FA). Participants completed a follow-up session with T1 and DWI imaging (pGRN+ mean interval 2.20 years; yCTL mean interval 3.27 years). Annualized changes of GMD and FA were also compared. Results: Relative to yCTL, pGRN+ individuals displayed reduced GMD at baseline in bilateral orbitofrontal, insular, and anterior temporal cortices. pGRN+ also showed greater annualized GMD changes than yCTL at follow-up in right orbitofrontal and left occipital cortices. We also observed reduced FA at baseline in bilateral superior longitudinal fasciculus, left corticospinal tract, and frontal corpus callosum in pGRN+ relative to yCTL, and pGRN+ displayed greater annualized longitudinal FA change in right superior longitudinal fasciculus and frontal corpus callosum. Conclusions: Longitudinal MRI provides evidence of progressive GM and WM changes in pGRN+ participants relative to yCTL. Structural MRI illustrates the natural history of presymptomatic GRN carriers, and may provide an endpoint during disease-modifying treatment trials for pGRN+ individuals at risk for FTD. Keywords: Frontotemporal lobar degeneration, Magnetic resonance imaging, Neuroimaging, Progranulin, Presymptomatic, Longitudinalhttp://www.sciencedirect.com/science/article/pii/S2213158218301633 |
| spellingShingle | Christopher A. Olm Corey T. McMillan David J. Irwin Vivianna M. Van Deerlin Philip A. Cook James C. Gee Murray Grossman Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers NeuroImage: Clinical |
| title | Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers |
| title_full | Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers |
| title_fullStr | Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers |
| title_full_unstemmed | Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers |
| title_short | Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers |
| title_sort | longitudinal structural gray matter and white matter mri changes in presymptomatic progranulin mutation carriers |
| url | http://www.sciencedirect.com/science/article/pii/S2213158218301633 |
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