Cerebral Circulation - Cognition and Behavior (Jan 2024)
The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study
- Danit G. Saks,
- Beata Bajorek,
- Vibeke S. Catts,
- Adam C. Bentvelzen,
- Jiyang Jiang,
- Wei Wen,
- Karen A. Mather,
- Anbupalam Thalamuthu,
- Jessie Huang-Lung,
- Lisa Nivison-Smith,
- Lyn R. Griffiths,
- Robert A. Smith,
- Adrienne Sexton,
- Paul James,
- Tharusha Jayasena,
- Anne Poljak,
- Gurpreet K. Hansra,
- Satoshi Hosoki,
- Ashley Park,
- Claudia M. Hillenbrand,
- Peter van Wijngaarden,
- Russell J. Chander,
- Sam Humphrey,
- Rory Chen,
- Nicole A. Kochan,
- Tessa J. Helman,
- Christopher Levi,
- Amy Brodtmann,
- Michael J. O'Sullivan,
- Romesh Markus,
- Ken Butcher,
- Mark Parsons,
- Jason C. Kovacic,
- Perminder S. Sachdev
Affiliations
- Danit G. Saks
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Beata Bajorek
- Heart and Stroke Program, Hunter Medical Research Institute, Newcastle, 2305, Australia; Pharmacy Department, John Hunter Hospital, Newcastle, 2305, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, 2308, Australia
- Vibeke S. Catts
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Adam C. Bentvelzen
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Jiyang Jiang
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Wei Wen
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Karen A. Mather
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Anbupalam Thalamuthu
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Jessie Huang-Lung
- School of Optometry and Vision Science, University of New South Wales, Sydney, 2052, Australia
- Lisa Nivison-Smith
- School of Optometry and Vision Science, University of New South Wales, Sydney, 2052, Australia
- Lyn R. Griffiths
- Genomics Research Centre, Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, 4059, Australia
- Robert A. Smith
- Genomics Research Centre, Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, 4059, Australia
- Adrienne Sexton
- Genomic Medicine, Royal Melbourne Hospital, Melbourne, 3052, Australia
- Paul James
- Genomic Medicine, Royal Melbourne Hospital, Melbourne, 3052, Australia
- Tharusha Jayasena
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Anne Poljak
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia; Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, 2052, Australia
- Gurpreet K. Hansra
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Satoshi Hosoki
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Ashley Park
- Department of Neurology, Royal Melbourne Hospital, Melbourne, 3052, Australia
- Claudia M. Hillenbrand
- Research Imaging NSW, University of New South Wales, Sydney, 2031, Australia
- Peter van Wijngaarden
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, 3002, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, 3052, Australia
- Russell J. Chander
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Sam Humphrey
- Department of Neurology, Royal Melbourne Hospital, Melbourne, 3052, Australia
- Rory Chen
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Nicole A. Kochan
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Tessa J. Helman
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Christopher Levi
- School of Medicine and Public Health, University of Newcastle, Newcastle, 2308, Australia; John Hunter Health and Innovation Precinct (JHHIP), Newcastle, 2305, Australia; Neurology Department, John Hunter Hospital, Newcastle, 2305, Australia
- Amy Brodtmann
- Department of Neurology, Royal Melbourne Hospital, Melbourne, 3052, Australia
- Michael J. O'Sullivan
- Institute for Molecular Bioscience, University of Queensland, Brisbane, 4067, Australia
- Romesh Markus
- Department of Neurology, St Vincent's Hospital, Sydney, 2010, Australia
- Ken Butcher
- Department of Neurology, Prince of Wales Hospital, Sydney, 2031, Australia
- Mark Parsons
- School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia
- Jason C. Kovacic
- School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia; Victor Chang Cardiac Research Institute, Sydney, 2010, Australia; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Perminder S. Sachdev
- Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, 2052, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, 2031, Australia; Corresponding author at: Centre for Healthy Brain Ageing, AGSM Building, Gate 11, Botany St, UNSW, Sydney, NSW, 2052, Australia.
- Journal volume & issue
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Vol. 6
p. 100225
Abstract
Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.
