title: 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.
abstract: 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.
  
  
  
  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 using11C-labelled Pittsburgh Compound B ([11C]PiB) and18F-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.
  
  
  
  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.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: W Richard
authors.initials: WR
authors.lastname: Bevan-Jones
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Ajenthan
authors.initials: A
authors.lastname: Surendranathan
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Passamonti
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vázquez Rodríguez
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Elijah
authors.initials: E
authors.lastname: Mak
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Coles
authors.affiliation: Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Fryer
authors.affiliation: Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK.
authors.forename: Young T
authors.initials: YT
authors.lastname: Hong
authors.affiliation: Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Williams
authors.affiliation: Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK.
authors.forename: Franklin
authors.initials: F
authors.lastname: Aigbirhio
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D003704:Dementia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D003863:Depression / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D004660:Encephalitis / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D057180:Frontotemporal Dementia / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D000067562:Late Onset Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D020961:Lewy Body Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000379:methods; D012107:Research Design; D013494:Supranuclear Palsy, Progressive / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D016176:T-Lymphocyte Subsets; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000682:Amyloid; D015415:Biomarkers; D016207:Cytokines; D016875:tau Proteins
keywords: Neuroinflammation; Positron emission tomography; Tau; [11C]PK11195; [18F]AV-1451