Article Text
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. Data are available on reasonable request. Anonymised data will be made available to qualified investigators on reasonable request to the corresponding author.
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Data availability statement
Data are available on reasonable request. Data are available on reasonable request. Anonymised data will be made available to qualified investigators on reasonable request to the corresponding author.
Footnotes
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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.
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