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Longitudinal diffusion tensor imaging changes in early Parkinson’s disease: ICICLE-PD study

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Abstract

Objective

To investigate whether white matter microstructural changes can be used as a predictor of worsening of motor features or cognitive decline in patients with Parkinson’s disease and verify whether white matter microstructural longitudinal changes differ between patients with Parkinson’s disease with normal cognition and those with mild cognitive impairment.

Methods

We enrolled 120 newly diagnosed patients with early stage Parkinson’s disease (27 with mild cognitive impairment and 93 with normal cognition) along with 48 controls. Participants were part of the incidence of cognitive impairment in cohorts with longitudinal evaluation in Parkinson’s disease study and were assessed at baseline and 18 months later with cognitive, motor tests and diffusion tensor imaging. The relationships between fractional anisotropy and mean diffusivity with disease status, cognitive and motor function were investigated.

Results

At baseline, patients with early stage Parkinson’s disease had significantly higher widespread mean diffusivity relative to controls, regardless of cognitive status. In patients with Parkinson’s disease/mild cognitive impairment, higher mean diffusivity was significantly correlated with lower attention and executive function scores. At follow-up frontal mean diffusivity increased significantly when comparing patients with Parkinson’s disease/mild cognitive impairment with those with normal cognition. Baseline mean diffusivity was a significant predictor of worsening of motor features in Parkinson’s disease.

Conclusions

Mean diffusivity represents an important correlate of cognitive function and predictor of motor impairment in Parkinson’s disease: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function.

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Funding

ICICLE-PD was funded by Parkinson’s UK (J-0802, G-1301, G-1507) and supported by the Lockhart Parkinson’s Disease Research Fund, NIHR (National Institute for Health Research) (RG64473); NIHR Biomedical Research Unit in Dementia at Cambridge University Hospitals NHS (National Health Service) Foundation Trust and the University of Cambridge; and NIHR Biomedical Research Unit in Dementia at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. TM is is funded by an Academic Clinical Fellow from NIHR. LS is supported by Alzheimer’s Research UK (ARUK-SRF2017B-1). EM is in receipt of the Gates Cambridge scholarship. JBR  is supported by the Wellcome Trust (103838) and Medical Research Council (MC-A060-5PQ30).

Author information

Authors and Affiliations

  1. Department of Radiology, University of Cambridge, Cambridge, UK

    Thais Minett

  2. Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK

    Thais Minett

  3. Department of Psychiatry, University of Cambridge, Cambridge, UK

    Li Su, Elijah Mak & John T. O’Brien

  4. Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK

    Guy Williams

  5. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK

    Michael Firbank, Rachael A. Lawson, Alison J. Yarnall & David J. Brooks

  6. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    Gordon W. Duncan

  7. Brain and Mind Institute, University of Western Ontario, London, Canada

    Adrian M. Owen

  8. Department of Psychology, University of Western Ontario, London, Canada

    Adrian M. Owen

  9. School of Medicine, University of Wollongong, Wollongong, NSW, Australia

    Tien K. Khoo

  10. Division of Neuroscience, Imperial College London, London, UK

    David J. Brooks

  11. Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark

    David J. Brooks

  12. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    James B. Rowe

  13. Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK

    James B. Rowe

  14. Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    James B. Rowe

  15. John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK

    Roger A. Barker

  16. Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

    David Burn

  17. China-UK Centre for Cognition and Ageing Research, Southwest University, Chongqing, China

    Li Su

Authors
  1. Thais Minett
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  2. Li Su
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  3. Elijah Mak
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  4. Guy Williams
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  5. Michael Firbank
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  6. Rachael A. Lawson
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  7. Alison J. Yarnall
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  8. Gordon W. Duncan
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  9. Adrian M. Owen
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  10. Tien K. Khoo
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  11. David J. Brooks
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  12. James B. Rowe
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  13. Roger A. Barker
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  14. David Burn
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  15. John T. O’Brien
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Contributions

TM: Imaging processing, concluded statistical analyses, manuscript draft and revision. LS: Data analyses, manuscript revision. EM: Manuscript revision. GW: Manuscript revision. MF: Manuscript revision. RAL: Study coordination, participant recruitment, data collection, manuscript revision. AJY: Study coordination, participant recruitment, clinical assessment, data collection and manuscript revision. GWD: Study coordination, participant recruitment, clinical assessment, data collection and manuscript revision. AMO: Manuscript revision. TKK: Study coordination, participant recruitment, clinical assessment, data collection and manuscript revision. DJB: Principal investigator and co-applicant for the funding grant. He was involved in the study design and manuscript revision. JBR: Data acquisition and manuscript revision. RAB: Principal investigator and co-applicant for the funding grant. He was involved in the study design and manuscript revision. DB: Chief investigator and main applicant for the funding grant. He was involved with the study design, supervision and manuscript revision. JTO: Principal investigator and co-applicant for the funding grant. He was involved in the study design, supervision and manuscript revision.

Corresponding author

Correspondence to Thais Minett.

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Conflicts of interest

Dr Thais Minett reports no disclosure. Dr Li Su reports no disclosure. Elijah Mak reports no disclosure. Dr Guy Williams reports no disclosure. Dr Michael Firbank reports no disclosure. Dr Rachael (A) Lawson reports no disclosure. Dr Alison J. Yarnall has received honoraria from Teva-Lundbeck and sponsorship from Teva-Lundbeck, UCB, GlaxoSmithKline, Genus and Abbvie for attending conferences. Dr Gordon W. Duncan reports no disclosure. Dr Adrian M. Owen reports no disclosure. Dr Tien K. Khoo reports no disclosure. Prof David J. Brooks reports no disclosure. Prof James (B) Rowe received grants from NIHR, Evelyn Trust, McDonnell Foundation, ARUK, PSP Association, AZ-Medimmune and Janssen, but no personal financial remuneration or consultancies or other conflict-of-interest arising from these. Prof David Burn reports no disclosure. Prof John T. O’Brien reports no disclosure. Prof Roger A Barker received grants from Parkinson’s UK, NIHR, Cure Parkinson’s Trust, Evelyn Trust, Rosetrees Trust, MRC and EU along with payment for advisory board attendance from Oxford Biomedica and LCT, and honoraria from Wiley and Springer. Prof David Burn reports no disclosure.

Ethical approval

The study was approved by the Newcastle and North Tyneside Research Ethics Committee and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants provided informed consent prior to their inclusion in the study.

Disclaimer

This article presents independent research funded by Parkinson’s UK and the National Institute for Health Research. The views expressed are those of the authors and not necessarily those of the NHS, Parkinson’s UK the National Institute for Health Research or the Department of Health.

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Minett, T., Su, L., Mak, E. et al. Longitudinal diffusion tensor imaging changes in early Parkinson’s disease: ICICLE-PD study. J Neurol 265, 1528–1539 (2018). https://doi.org/10.1007/s00415-018-8873-0

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  • DOI: https://doi.org/10.1007/s00415-018-8873-0

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