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

IntroductionInflammation 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 analysisUsing 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 disseminationThe 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.

18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

“…3 for data plot from two characteristic regions of interest). In the Supplementary material we also report the accuracy of pair-wise comparisons between groups using hierarchical cluster analyses, based on the regional distribution of 18 F-AV-1451 BP ND across the whole brain (Bevan Jones et al , 2016 a ).

Figure 3 Individual 18 F-AV-1451 BP ND values in the hippocampus ( x -axis) and midbrain ( y -axis) in patients with Alzheimer’s disease (AD) and amyloid-positive MCI (MCI+; red dots), PSP (cyan dots), and healthy control subjects (green dots).

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“…The current study was conducted within the context of the Neuroimaging of Inflammation in MemoRy and Other Disorders (NIMROD) project (Bevan-Jones et al , 2016 a ). We recruited 19 patients with PSP [‘probable PSP’ by Movement Disorder Society criteria (Litvan et al , 1996 a , b ), representing the ‘classical phenotype’, which is sometimes referred to as Richardson’s syndrome], nine patients meeting diagnostic criteria for probable Alzheimer’s disease (McKhann et al , 2011), and six patients with MCI and biomarker evidence of Alzheimer’s disease (i.e.…”

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

“…The study cohort comprised 65 participants (33 HC, 14 positron‐emission tomography amyloid‐positive patients with MCI, and 18 patients with AD dementia) above the age of 50 years as part of the Neuroinflammation in Memory and Related Other Disorders study, a multimodal imaging cohort study [29]. Participants with MCI and AD were recruited from memory clinics in and around Cambridgeshire, including the regions of Lincolnshire, Bedfordshire, Norfolk, Suffolk, Hertfordshire, and Essex, or via the Dementias and Neurodegeneration specialty of the UK Clinical Research Network or the Join Dementia Research platform (https://www.joindementiaresearch.nihr.ac.uk).…”

“…For participants with MCI and AD, the ability to carry out everyday activities was measured using the informant-completed Bristol Activities of Daily Living Scale and neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. The detailed procedures have been described in a previously published study [29].…”

Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance

“…The study was conducted in the context of the Neuroimaging of Inflammation in MemoRy and Other Disorders (NIMROD) study (Bevan-Jones et al, 2017). We included 14 patients meeting clinical diagnostic criteria for probable Alzheimer's disease (McKhann et al, 2011), and 14 patients with mild cognitive (MCI) patients (15 males and 13 females in total) defined by: i) a mini-mental score examination >24/30; ii) memory impairment at least 1.5 standard deviations below that expected for age and education (Petersen et al, 1999); iii) biomarker evidence of amyloid pathology (positive Pittsburgh Compound-B PET scan) (MCI+) (Okello et al, 2009).…”