Cortical microstructure in the behavioural variant of frontotemporal dementia: looking beyond atrophy


Por: Illan-Gala, I, Montal, V, Borrego-Ecija, S, Vilaplana, E, Pegueroles, J, Alcolea, D, Sanchez-Saudinos, MB, Clarimon, J, Turon-Sans, J, Bargallo, N, Gonzalez-Ortiz, S, Rosen, HJ, Gorno-Tempini, ML, Miller, BL, Llado, A, Rojas-Garcia, R, Blesa, R, Sanchez-Valle, R, Lleo, A, Fortea, J

Publicada: 1 abr 2019
Resumen:
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 bio-markers (neurofilament light and the soluble fraction beta of the amyloid precursor protein). We included 148 participants with a 3T 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.

Filiaciones:
Illan-Gala, I:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Montal, V:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Borrego-Ecija, S:
 Univ Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Dept Neurol, Hosp Clin, Barcelona, Spain

Vilaplana, E:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Pegueroles, J:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Alcolea, D:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Sanchez-Saudinos, MB:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

Clarimon, J:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Turon-Sans, J:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain

Bargallo, N:
 IDIBAPS, Radiol Dept, Barcelona, Spain

Gonzalez-Ortiz, S:
 Hosp Mar, Dept Radiol, Barcelona, Spain

Rosen, HJ:
 Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA

Gorno-Tempini, ML:
 Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA

Miller, BL:
 Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA

Blesa, R:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Sanchez-Valle, R:
 Univ Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Dept Neurol, Hosp Clin, Barcelona, Spain

Lleo, A:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Fortea, J:
 Univ Autonoma Barcelona, Memory Unit, Dept Neurol, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain

 CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona 08025, Spain
ISSN: 00068950





BRAIN
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 142 Número:
Páginas: 1121-1133
WOS Id: 000472805000027
ID de PubMed: 30906945
imagen Green Published, Bronze

MÉTRICAS