Dataset Information

Disease-related cortical thinning in presymptomatic granulin mutation carriers.

ABSTRACT: Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

SUBMITTER: Borrego-Ecija S

PROVIDER: S-EPMC7804836 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Disease-related cortical thinning in presymptomatic granulin mutation carriers.

Borrego-Écija Sergi S Sala-Llonch Roser R van Swieten John J Borroni Barbara B Moreno Fermín F Masellis Mario M Tartaglia Carmela C Graff Caroline C Galimberti Daniela D Laforce Robert R Rowe James B JB Finger Elizabeth E Vandenberghe Rik R Tagliavini Fabrizio F de Mendonça Alexandre A Santana Isabel I Synofzik Matthis M Ducharme Simon S Levin Johannes J Danek Adrian A Gerhard Alex A Otto Markus M Butler Chris C Frisoni Giovanni G Sorbi Sandro S Heller Carolin C Bocchetta Martina M Cash David M DM Convery Rhian S RS Moore Katrina M KM Rohrer Jonathan D JD Sanchez-Valle Raquel R

NeuroImage. Clinical 20201229

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical ...[more]

PMID: 33418170

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Project description:BackgroundClinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis-free, data-driven approach based on cortical thickness data.MethodsT1-weighted 3-tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups.ResultsWe observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment.ConclusionsThree cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto-temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Disease-related cortical thinning in presymptomatic granulin mutation carriers.

Publications

Disease-related cortical thinning in presymptomatic granulin mutation carriers.

Similar Datasets

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