. 2019 Oct 29;93(18):e1699-e1706.

doi: 10.1212/WNL.0000000000008386. Epub 2019 Oct 2.

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Tamara P Tavares¹, Derek G V Mitchell¹, Kristy Coleman¹, Christen Shoesmith¹, Robert Bartha¹, David M Cash¹, Katrina M Moore¹, John van Swieten¹, Barbara Borroni¹, Daniela Galimberti¹, Maria Carmela Tartaglia¹, James Rowe¹, Caroline Graff¹, Fabrizio Tagliavini¹, Giovanni Frisoni¹, Stefano Cappa¹, Robert Laforce Jr¹, Alexandre de Mendonça¹, Sandro Sorbi¹, Garrick Wallstrom¹, Mario Masellis¹, Jonathan D Rohrer¹, Elizabeth C Finger²; Genetic FTD Initiative, GENFI

Collaborators, Affiliations

Collaborators

Genetic FTD Initiative, GENFI:
Christin Andersson, Silvana Archetti, Andrea Arighi, Luisa Benussi, Sandra Black, Martina Bocchetta, Maura Cosseddu, Marie Fallström, Carlos Ferreira, Catarina B Ferreira, Chiara Fenoglio, Nick C Fox, Morris Freedman, Giorgio Fumagalli, Stefano Gazzina, Roberta Ghidoni, Marina Grisoli, Vesna Jelic, Lize Jiskoot, R Keren, Gemma Lombardi, Carolina Maruta, Lieke Meeter, Rick van Minkelen, Gabriel Miltenberger, Benedetta Nacmias, Linn Öijerstedt, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Michela Pievani, Cristina Polito, Enrico Premi, Sara Prioni, Rosa Rademakers, Veronica Redaelli, Ekaterina Rogaeva, Giacomina Rossi, Martin N Rossor, Elio Scarpini, David Tang-Wai, Carmela Tartaglia, David Thomas, Hakan Thonberg, Pietro Tiraboschi, Ana Verdelho, Jason D Warren

Affiliations

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.

PMID: 31578297
PMCID: PMC6946476
DOI: 10.1212/WNL.0000000000008386

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Tamara P Tavares et al. Neurology. 2019.

. 2019 Oct 29;93(18):e1699-e1706.

doi: 10.1212/WNL.0000000000008386. Epub 2019 Oct 2.

Authors

Collaborators

Genetic FTD Initiative, GENFI:
Christin Andersson, Silvana Archetti, Andrea Arighi, Luisa Benussi, Sandra Black, Martina Bocchetta, Maura Cosseddu, Marie Fallström, Carlos Ferreira, Catarina B Ferreira, Chiara Fenoglio, Nick C Fox, Morris Freedman, Giorgio Fumagalli, Stefano Gazzina, Roberta Ghidoni, Marina Grisoli, Vesna Jelic, Lize Jiskoot, R Keren, Gemma Lombardi, Carolina Maruta, Lieke Meeter, Rick van Minkelen, Gabriel Miltenberger, Benedetta Nacmias, Linn Öijerstedt, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Michela Pievani, Cristina Polito, Enrico Premi, Sara Prioni, Rosa Rademakers, Veronica Redaelli, Ekaterina Rogaeva, Giacomina Rossi, Martin N Rossor, Elio Scarpini, David Tang-Wai, Carmela Tartaglia, David Thomas, Hakan Thonberg, Pietro Tiraboschi, Ana Verdelho, Jason D Warren

Affiliations

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.

PMID: 31578297
PMCID: PMC6946476
DOI: 10.1212/WNL.0000000000008386

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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Figures

**Figure 1. Total ventricular volume by years from expected symptom onset in presymptomatic carriers vs noncarriers**
Total ventricular volume by estimated years from expected symptom onset in presymptomatic carriers (blue, n = 46) and noncarriers (red, n = 53). Ventricular volume is expressed as a percentage of intracranial volume. To prevent disclosure of genetic status, individual data points are not plotted. Differences are noted beginning at 4 years prior to symptom onset as indicated by the dashed line (p = 0.04).

See this image and copyright information in PMC

References

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Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Collaborators

Affiliations

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Authors

Collaborators

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous