학술논문

Cortical microstructure in the behavioural variant of frontotemporal dementia: looking beyond atrophy
Document Type
article
Source
Brain. 142(4)
Subject
Biological Psychology
Health Sciences
Psychology
Neurosciences
Dementia
Rare Diseases
Alzheimer's Disease
Frontotemporal Dementia (FTD)
Acquired Cognitive Impairment
Aging
Brain Disorders
Neurodegenerative
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Clinical Research
2.1 Biological and endogenous factors
Aetiology
Neurological
Aged
Alzheimer Disease
Atrophy
Brain
Cohort Studies
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
Female
Frontotemporal Dementia
Frontotemporal Lobar Degeneration
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
White Matter
diffusion
magnetic resonance
frontotemporal dementia
biomarker
Catalan Frontotemporal Dementia Initiative (CATFI) and the Frontotemporal Lobar Degeneration Neuroimaging Initiative
Medical and Health Sciences
Psychology and Cognitive Sciences
Neurology & Neurosurgery
Biomedical and clinical sciences
Health sciences
Language
Abstract
Cortical mean diffusivity has been proposed as a novel biomarker for the study of the cortical microstructure in Alzheimer's disease. In this multicentre study, we aimed to assess the cortical microstructural changes in the behavioural variant of frontotemporal dementia (bvFTD); and to correlate cortical mean diffusivity with clinical measures of disease severity and CSF biomarkers (neurofilament light and the soluble fraction beta of the amyloid precursor protein). We included 148 participants with a 3 T MRI and appropriate structural and diffusion weighted imaging sequences: 70 patients with bvFTD and 78 age-matched cognitively healthy controls. The modified frontotemporal lobar degeneration clinical dementia rating was obtained as a measure of disease severity. A subset of patients also underwent a lumbar puncture for CSF biomarker analysis. Two independent raters blind to the clinical data determined the presence of significant frontotemporal atrophy to dichotomize the participants into possible or probable bvFTD. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach. We compared cortical thickness and cortical mean diffusivity between bvFTD (both using the whole sample and probable and possible bvFTD subgroups) and controls. Then we computed the Cohen's d effect size for both cortical thickness and cortical mean diffusivity. We also performed correlation analyses with the modified frontotemporal lobar degeneration clinical dementia rating score and CSF neuronal biomarkers. The cortical mean diffusivity maps, in the whole cohort and in the probable bvFTD subgroup, showed widespread areas with increased cortical mean diffusivity that partially overlapped with cortical thickness, but further expanded to other bvFTD-related regions. In the possible bvFTD subgroup, we found increased cortical mean diffusivity in frontotemporal regions, but only minimal loss of cortical thickness. The effect sizes of cortical mean diffusivity were notably higher than the effect sizes of cortical thickness in the areas that are typically involved in bvFTD. In the whole bvFTD group, both cortical mean diffusivity and cortical thickness correlated with measures of disease severity and CSF biomarkers. However, the areas of correlation with cortical mean diffusivity were more extensive. In the possible bvFTD subgroup, only cortical mean diffusivity correlated with the modified frontotemporal lobar degeneration clinical dementia rating. Our data suggest that cortical mean diffusivity could be a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in bvFTD. Further longitudinal studies should determine the diagnostic and prognostic utility of this novel neuroimaging biomarker.