Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results-Reference-Cited by-同舟云学术

Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Published:2024-04-16 Issue:5 Volume:20 Page:3525-3542
ISSN:1552-5260
Container-title:Alzheimer's & Dementia
language:en
Short-container-title:Alzheimer's & Dementia

Author:

Pasternak Maurice¹²^ORCID,Mirza Saira S.¹,Luciw Nicholas¹³,Mutsaerts Henri J. M. M.⁴,Petr Jan⁵,Thomas David⁶,Cash David⁷,Bocchetta Martina⁷,Tartaglia Maria Carmela⁸⁹¹⁰,Mitchell Sara B.¹⁰,Black Sandra E.¹⁰¹¹¹²,Freedman Morris¹⁰¹¹,Tang‐Wai David¹⁰¹¹¹³,Rogaeva Ekaterina⁸,Russell Lucy L.⁷,Bouzigues Arabella⁶,van Swieten John C.¹⁴,Jiskoot Lize C.¹⁴,Seelaar Harro¹⁴,Laforce Robert¹⁵,Tiraboschi Pietro¹⁶,Borroni Barbara¹⁷,Galimberti Daniela¹⁸¹⁹,Rowe James B.²⁰²¹²²,Graff Caroline²³²⁴,Finger Elizabeth²⁵,Sorbi Sandro²⁶²⁷,de Mendonça Alexandre²⁸,Butler Chris²⁹³⁰,Gerhard Alex³¹³²³³,Sanchez‐Valle Raquel³⁴,Moreno Fermin³⁵³⁶,Synofzik Matthis³⁷,Vandenberghe Rik³⁸,Ducharme Simon³⁹⁴⁰,Levin Johannes⁴¹⁴²,Otto Markus⁴³,Santana Isabel⁴⁴,Strafella Antonio P.¹³⁴⁵⁴⁶,MacIntosh Bradley J.¹³,Rohrer Jonathan D.⁷,Masellis Mario¹²¹⁰¹²⁴⁷,

Affiliation:

1. Hurvitz Brain Sciences Program Sunnybrook Research Institute Toronto Ontario Canada

2. Institute of Medical Science Temerty Faculty of Medicine University of Toronto Toronto Ontario Canada

3. Medical Biophysics University of Toronto Toronto Ontario Canada

4. Department of Radiology and Nuclear Medicine Amsterdam Neuroscience Amsterdam University Medical Center Amsterdam the Netherlands

5. Helmholtz‐Zentrum Dresden‐Rossendorf Institute of Radiopharmaceutical Cancer Research Dresden Germany

6. Department of Brain Repair and Rehabilitation UCL Queen Square Institute of Neurology Queen Square London UK

7. Dementia Research Centre Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology Queen Square London UK

8. Tanz Centre for Research in Neurodegenerative Diseases University of Toronto Toronto Ontario Canada

9. Memory Clinic University Health Network Toronto Ontario Canada

10. Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre Toronto Ontario Canada

11. Rotman Research Institute Baycrest Health Sciences Toronto Ontario Canada

12. Cognitive Neurology Research Unit Sunnybrook Health Sciences Centre Toronto Ontario Canada

13. Krembil Research Institute University Health Network Toronto Ontario Canada

14. Department of Neurology Erasmus Medical Center Rotterdam the Netherlands

15. Clinique Interdisciplinaire de Mémoire CHU de Québec, Département des Sciences Neurologiques Université Laval Quebec Quebec Canada

16. Division of Neurology Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

17. Department of Clinical and Experimental Sciences University of Brescia Brescia Italy

18. Department of Biomedical Surgical and Dental Sciences University of Milan Milan Italy

19. Neurodegenerative Diseases Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

20. Department of Clinical Neurosciences University of Cambridge Cambridge UK

21. Cambridge University Hospitals NHS Trust University of Cambridge Cambridge UK

22. Medical Research Council Cognition and Brain Sciences Unit University of Cambridge Cambridge UK

23. Department of Neurobiology Care Sciences and Society Karolinska Institutet Huddinge Sweden

24. Unit for Hereditary Dementias Karolinska University Hospital Solna Sweden

25. Department of Clinical Neurological Sciences Western University London Ontario Canada

26. Department of Neurofarba University of Florence Florence Italy

27. Fondazione Don Carlo Gnocchi Istituto di Ricovero e Cura a Carattere Scientifico Florence Italy

28. Neurology Department Faculty of Medicine University of Lisbon Lisbon Portugal

29. Nuffield Department of Clinical Neurosciences Medical Sciences Division University of Oxford Oxford UK

30. Department of Brain Sciences Imperial College London London UK

31. Division of Psychology Communication and Human Neuroscience Wolfson Molecular Imaging Centre University of Manchester Manchester UK

32. Department of Geriatric Medicine Klinikum Hochsauerland GmbH Arnsberg Germany

33. Department of Nuclear Medicine Center for Translational Neuro‐ and Behavioral Sciences University Hospital Essen Essen Germany

34. Alzheimer's Disease and Other Cognitive Disorders Unit Hospital Clinic de Barcelona Barcelona Spain

35. Cognitive Disorders Unit Department of Neurology Donostia University Hospital Gipuzkoa Building Begiristain Doktorea Pasealekua Donostia–San Sebastian Gipuzkoa Spain

36. Neuroscience Area Biodonostia Health Research Institute Donostia–San Sebastian Gipuzkoa Spain

37. Department of Neurodegenerative Diseases Hertie‐Institute for Clinical Brain Research and Center of Neurology University of Tübingen Tübingen Germany

38. Laboratory for Cognitive Neurology Department of Neurosciences KU Leuven Leuven Belgium

39. Department of Psychiatry Douglas Mental Health University Institute McGill University Montreal Quebec Canada

40. McConnell Brain Imaging Centre Montreal Neurological Institute and Hospital Montreal Quebec Canada

41. Department of Neurology Ludwig‐Maximilians‐University Munich Germany

42. Munich Cluster of Systems Neurology (SyNergy) Munich Germany

43. Department of Neurology University of Ulm Ulm Germany

44. Center for Neuroscience and Cell Biology Faculty of Medicine University of Coimbra Coimbra Portugal

45. Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto Ontario Canada

46. Edmond J. Safra Parkinson Disease Program & Morton and Gloria Shulman Movement Disorder Unit Toronto Western Hospital UHN Toronto Ontario Canada

47. Department of Medicine Division of Neurology University of Toronto Toronto Ontario Canada

Abstract

AbstractINTRODUCTIONEffective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers.METHODSWe investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non‐carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment.RESULTSPerfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset.DISCUSSIONCerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset.Highlights

Gray matter perfusion declines in at‐risk genetic frontotemporal dementia (FTD).

Regional perfusion decline differs between at‐risk genetic FTD subgroups .

Hypoperfusion in the left thalamus is common across all presymptomatic groups.

Converters exhibit greater right frontal hypoperfusion than non‐converters past their expected conversion date.

Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Funder

Canadian Institutes of Health Research

Weston Brain Institute

Deutsche Forschungsgemeinschaft

Medical Research Council

Morris Kerzner Memorial Fund

Instituto de Salud Carlos III