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Neurology. 2019 Oct 2. pii: 10.1212/WNL.0000000000008386. doi: 10.1212/WNL.0000000000008386. [Epub ahead of print]

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia.

Author information

1
From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada.
2
From the Graduate Program in Neuroscience and Brain and Mind Institute (T.P.T., D.G.V.M., E.C.F.) and Departments of Clinical Neurological Sciences (C.S., E.C.F.) and Medical Biophysics (R.B.), Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (K.C., E.C.F.), Lawson Health Research Institute, London, Canada; Dementia Research Centre, Department of Neurodegenerative Disease (D.M.C., K.M.M., J.D.R.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (D.M.C.), University College London, UK; Department of Neurology (J.v.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Neurology Unit, Department of Clinical and Experimental Sciences (B.B.), University of Brescia; Department of Pathophysiology and Transplantation (D.G.), "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Italy; Toronto Western Hospital (M.C.T.), Tanz Centre for Research in Neurodegenerative Disease, Canada; Department of Clinical Neurosciences (J.R.), University of Cambridge, UK; Department NVS (C.G.), Center for Alzheimer Research, Division of Neurogenetics, Karolinska Institutet, Sweden; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta (F.T.), Milan; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Centro San Giovanni di Dio Fatebenefratelli (G.F., S.C.), Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging (G.F.), University Hospitals and University of Geneva, Switzerland; Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques (R.L.), CHU de Québec, and Faculté de Médecine, Université Laval, Canada; Faculty of Medicine (A.d.M.), University of Lisbon, Portugal; Department of Neuroscience, Psychology, Drug Research and Child Health (S.S.), University of Florence, and the IRCCS Foundazione Don Carlo Gnocchi (S.S.), Florence, Italy; Statistics & Data Corporation (G.W.), Tempe, AZ; and LC Campbell Cognitive Neurology Research Unit (M.M.), Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada. elizabeth.finger@lhsc.on.ca.

Abstract

OBJECTIVE:

To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.

METHODS:

Participants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers.

RESULTS:

A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings.

CONCLUSIONS:

Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD.

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