Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer's disease

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 ThomasJohn Gallacher, Simon Lovestone

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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.

Original languageEnglish
Article numbere024498
Number of pages16
JournalBMJ Open
Volume9
Issue number3
DOIs
Publication statusPublished - 23 Mar 2019

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

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Koychev, I., Lawson, J., Chessell, T., Mackay, C., Gunn, R., Sahakian, B., Rowe, J. B., Thomas, A. J., Rochester, L., Chan, D., Tom, B., Malhotra, P., Ballard, C., Chessell, I., Ritchie, C. W., Raymont, V., Leroi, I., Lengyel, I., Murray, M., ... Lovestone, S. (2019). Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer's disease. BMJ Open, 9(3), [e024498]. https://doi.org/10.1136/bmjopen-2018-024498