Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer’s disease
Year: 2019
Type: article
Study design: Study Protocol
Abstract: INTRODUCTION: Recent failures of potential novel therapeutics for Alzheimer's disease (AD) have prompted a drive towards clinical studies in prodromal or preclinical states. However, carrying out clinical trials in early disease stages is extremely challenging-a key reason being the unfeasibility of using classical outcome measures of dementia trials (eg, conversion to dementia) and the lack of validated surrogate measures so early in the disease process. The Deep and Frequent Phenotyping (DFP) study aims to resolve this issue by identifying a set of markers acting as indicators of disease progression in the prodromal phase of disease that could be used as indicative outcome measures in proof-of-concept trials. METHODS AND ANALYSIS: The DFP study is a repeated measures observational study where participants will be recruited through existing parent cohorts, research interested lists/databases, advertisements and memory clinics. Repeated measures of both established (cognition, positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) markers of pathology, structural MRI markers of neurodegeneration) and experimental modalities (functional MRI, magnetoencephalography and/or electroencephalography, gait measurement, ophthalmological and continuous smartphone-based cognitive and other assessments together with experimental CSF, blood, tear and saliva biomarkers) will be performed. We will be recruiting male and female participants aged >60 years with prodromal AD, defined as absence of dementia but with evidence of cognitive impairment together with AD pathology as assessed using PET imaging or CSF biomarkers. Control participants without evidence of AD pathology will be included at a 1:4 ratio. ETHICS AND DISSEMINATION: The study gained favourable ethical opinion from the South Central-Oxford B NHS Research Ethics Committee (REC reference 17/SC/0315; approved on 18 August 2017; amendment 13 February 2018). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.
Source: BMJ Open
Authors: Ivan Koychev, Jennifer Lawson, Tharani Chessell, Clare Mackay, Roger Gunn, Barbara Sahakian, James B Rowe, Alan J Thomas, Lynn Rochester, Dennis Chan, Brian Tom, Paresh Malhotra, Clive Ballard, Iain Chessell, Craig W Ritchie, Vanessa Raymont, Iracema Leroi, Imre Lengyel, Matt Murray, David L Thomas, John Gallacher, Simon Lovestone
Institutions: University of Oxford, AstraZeneca (United Kingdom), Invicro (United Kingdom), Imperial College London, University of Cambridge, Newcastle University, MRC Cognition and Brain Sciences Unit, MRC Biostatistics Unit, University of Exeter, University of Edinburgh, Manchester Academic Health Science Centre, University of Manchester, Queen's University Belfast, Alzheimer's Society, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,839
Funders: Eli Lilly and Company, AstraZeneca, Roche, Wellcome Trust, Alzheimer's Society, National Institute for Health and Care Research, Academy of Medical Sciences, University of East Anglia, University of Exeter, Imperial College London, King's College London, University College London, University of Oxford, Newcastle University, Moorfields Eye Hospital NHS Foundation Trust, Dementias Platform UK, Avid Radiopharmaceuticals, Medical Research Council
Awards: G1021597669, G1072871761, G2139210046, G2202318582, Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease., Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease., Deep and Frequent Phenotyping; combinatorial biomarkers for dementia experimental medicine, G7212319858, G7250878952, G7697514025
OpenAlex ID: W2923630969