Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers
| Autor: | David J. Irwin, James C. Gee, Vivianna M. Van Deerlin, Christopher Olm, Philip A. Cook, Murray Grossman, Corey T. McMillan |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Pathology ROI region of interest GRN progranulin Corpus callosum lcsh:RC346-429 Progranulins 0302 clinical medicine SLF superior longitudinal fasciculus DWI diffusion-weighted imaging Medicine Gray Matter FA fractional anisotropy ILF inferior longitudinal fasciculus CST corticospinal tract medicine.diagnostic_test Superior longitudinal fasciculus Regular Article Frontotemporal lobar degeneration Middle Aged White Matter RD radial diffusivity Diffusion Tensor Imaging medicine.anatomical_structure Neurology lcsh:R858-859.7 Female AD axial diffusivity Adult BA Brodmann area Progranulin medicine.medical_specialty Cognitive Neuroscience Presymptomatic eCTL elderly healthy controls Neuroimaging lcsh:Computer applications to medicine. Medical informatics White matter 03 medical and health sciences Magnetic resonance imaging Atrophy GRN+ symptomatic progranulin mutation carriers Fractional anisotropy Humans Radiology Nuclear Medicine and imaging WM white matter lcsh:Neurology. Diseases of the nervous system Aged GMD gray matter density MD mean diffusivity business.industry pGRN+ presymptomatic progranulin mutation carriers medicine.disease FTD frontotemporal degeneration Diffusion Magnetic Resonance Imaging 030104 developmental biology IFO inferior fronto-occipital fasciculus Mutation yCTL young healthy controls Longitudinal Anisotropy GM gray matter Neurology (clinical) business 030217 neurology & neurosurgery Diffusion MRI |
| Zdroj: | NeuroImage : Clinical NeuroImage: Clinical, Vol 19, Iss, Pp 497-506 (2018) |
| ISSN: | 2213-1582 |
| DOI: | 10.1016/j.nicl.2018.05.017 |
| Popis: | 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. Highlights • Presymptomatic GRN mutation carriers (pGRN+) show decreased gray matter and white matter relative to young controls (yCTL) • pGRN+ show greater longitudinal changes in gray matter and white matter relative to yCTL • Regions with decreased gray matter and white matter in pGRN+ are in regions showing disease in symptomatic GRN+ |
| Databáze: | OpenAIRE |
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