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Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses
  1. W Richard Bevan-Jones1,
  2. Ajenthan Surendranathan1,
  3. Luca Passamonti2,
  4. Patricia Vázquez Rodríguez2,
  5. Robert Arnold1,
  6. Elijah Mak1,
  7. Li Su1,
  8. Jonathan P Coles3,
  9. Tim D Fryer4,
  10. Young T Hong4,
  11. Guy Williams4,
  12. Franklin Aigbirhio4,
  13. James B Rowe2,
  14. John T O'Brien1
  1. 1Department of Psychiatry, University of Cambridge, Cambridge, UK
  2. 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  3. 3Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
  4. 4Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr W Richard Bevan-Jones; wrb22{at}medschl.cam.ac.uk

Abstract

Introduction Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis.

Methods and analysis Using PET imaging of the ligand [11C]PK11195, we will test for increased neuroinflammation in vivo in patients with Alzheimer's disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late-onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and τ deposition (assessed using 11C-labelled Pittsburgh Compound B ([11C]PiB) and 18F-labelled AV-1451, respectively), as well as structural and connectivity markers found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central inflammation and peripheral inflammation. Finally, we will examine whether central inflammatory markers seen on PET imaging are associated with global and domain specific cognitive impairments or predict cognitive decline over 12 months.

Ethics and dissemination The study protocol was approved by the local ethics committee, East of England—Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also Administration of Radioactive Substances Advisory Committee (ARSAC) approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of clinical neuroscience, neurology and psychiatry.

  • Tau
  • Neuroinflammation
  • [18F]AV-1451
  • [11C]PK11195
  • Positron emission tomography

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • WRB-J and AS joint first authorship and JBR and JTO joint last authorship.

  • Contributors JTO and JBR are the joint PIs of the study. WRB-J and AS are the main authors and compilers of the manuscript. LS contributed text to the manuscript. JTO, JBR, RA, FA and JPC conceptualised and designed the study. All authors contributed feedback to the manuscript. All authors played a significant role in implementing the study protocol.

  • Funding The study is funded by the UK National Institute of Health Research Cambridge Biomedical Research Centre.

  • Competing interests None declared.

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

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