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Original research
Prediction of dementia using diffusion tensor MRI measures: the OPTIMAL collaboration
  1. Marco Egle1,
  2. Saima Hilal2,3,
  3. A M Tuladhar4,
  4. Lukas Pirpamer5,
  5. Edith Hofer5,6,
  6. Marco Duering7,8,
  7. James Wason9,10,
  8. Robin G Morris11,
  9. Martin Dichgans7,8,12,
  10. Reinhold Schmidt5,
  11. Daniel Tozer1,
  12. Christopher Chen2,
  13. Frank-Erik de Leeuw4,
  14. Hugh S Markus1
  1. 1Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  2. 2Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lim School of Medicine, National University of Singapore, Singapore
  3. 3Saw Swee Hock School of Public Health, National University of Singapore and National University Health System of Singapore, Singapore
  4. 4Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands
  5. 5Department of Neurology, Medical University Graz, Graz, Austria
  6. 6Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
  7. 7Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
  8. 8Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
  9. 9MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge Institute of Public Health, Cambridge, UK
  10. 10Population Health Sciences Institute, Newcastle University, Baddiley-Clark Building, Newcastle upon Tyne, UK
  11. 11Department of Psychology (R.G.M), King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
  12. 12German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  1. Correspondence to Professor Hugh S Markus, Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK; hsm32{at}medschl.cam.ac.uk

Abstract

Objectives It has been suggested that diffusion tensor imaging (DTI) measures sensitive to white matter (WM) damage may predict future dementia risk not only in cerebral small vessel disease (SVD), but also in mild cognitive impairment. To determine whether DTI measures were associated with cognition cross-sectionally and predicted future dementia risk across the full range of SVD severity, we established the International OPtimising mulTImodal MRI markers for use as surrogate markers in trials of Vascular Cognitive Impairment due to cerebrAl small vesseL disease collaboration which included six cohorts.

Methods Among the six cohorts, prospective data with dementia incidences were available for three cohorts. The associations between six different DTI measures and cognition or dementia conversion were tested. The additional contribution to prediction of other MRI markers of SVD was also determined.

Results The DTI measure mean diffusivity (MD) median correlated with cognition in all cohorts, demonstrating the contribution of WM damage to cognition. Adding MD median significantly improved the model fit compared to the clinical risk model alone and further increased in all single-centre SVD cohorts when adding conventional MRI measures. Baseline MD median predicted dementia conversion. In a study with severe SVD (SCANS) change in MD median also predicted dementia conversion. The area under the curve was best when employing a multimodal MRI model using both DTI measures and other MRI measures.

Conclusions Our results support a central role for WM alterations in dementia pathogenesis in all cohorts. DTI measures such as MD median may be a useful clinical risk predictor. The contribution of other MRI markers varied according to disease severity.

  • dementia
  • alzheimer's disease
  • cerebrovascular disease
  • MRI
  • vascular dementia

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors ME was responsible for the data analysis, interpretation of data, drafting the manuscript and critical revision of the manuscript for important intellectual content. He has full access to all of the data in the study. SH was responsible for the data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. AMT was responsible for the data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. LP was responsible for the data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. EH was responsible for the data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. MD was responsible for the study concept and design, data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. JW was responsible for the data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. RGM was responsible for the data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. MD was responsible for the study concept and design, data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. RS was responsible for the study concept and design, data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. DT was responsible for the data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. CPLHC was responsible for the study concept and design, data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. F-EdL was responsible for the study concept and design, the data acquisition and data analysis, interpretation of data and critical revision of the manuscript for important intellectual content. HSM was responsible for the study concept and design, the data acquisition and analysis, the interpretation of the data, drafting the manuscript, critical revision of the manuscript for important intellectual content and has full access to all of the data in the study.

  • Funding This work was funded by a grant from Alzheimer’s Research UK (ARUK-PG2016A-1). Additional support was provided by a Cambridge University- LMU collabative grant. ME is funded by a Priority Programme Grant from the Stroke Association (PPA 2015/02). Infrastructural support for this work was provided by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (146281). HSM is supported by an NIHR Senior Investigator Award. CPLHC is supported by an National Medical Research Council (NMRC) of Singapore Senior Clinician-Scientist Award and the HARMONISATION study has been funded by NMRC grants. F-EdL is supported by a clinical established investigator grant from the Dutch Heart Foundation (2014 T060) and by a VIDI innovational grant from The Netherlands ZonMw (grant number 016126351). AMT has received a grant from the Junior Staff Member Dutch Heart Foundation (2016T044).

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders and sponsors played no role in study design or analysis.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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