Deep and Frequent Phenotyping; combinatorial biomarkers for dementia experimental medicine
Award Number
MR/N029941/1Programme
Research GrantStatus / Stage
ActiveDates
1 October 2016 -30 September 2020
Duration (calculated)
03 years 11 monthsFunder(s)
MRC (UKRI)Funding Amount
£6,301,078.45Funder/Grant study page
MRC UKRIContracted Centre
University of OxfordContracted Centre Webpage
Principal Investigator
Simon LovestonePI Contact
simon.lovestone@psych.ox.ac.ukPI ORCID
0000-0003-0473-4565WHO Catergories
Development of BiomarkersDisease Type
Alzheimer's Disease (AD)CPEC Review Info
| Reference ID | 256 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | MR/N029941/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20161001 |
| End Date | 20200930 |
| Duration (calculated) | 03 years 11 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | University of Oxford |
| Contracted Centre Webpage | |
| Funding Amount | £6,301,078.45 |
Abstract
The D&FPhen study follows from a pilot phase that has established technical feasibility and participant acceptability. The study is for a repeated measures observational design in prodromal disease defined as no dementia but presence of episodic memory impairment >1.5SD from age adjusted norms in the context of AD pathology assessed using PET and CSF. Key design points include: – Participant recruitment through pre-existing parent cohorts. Ethical approval for this process, agreement from cohorts, technical platforms and proof of numbers meeting recruitment criteria are all in place – Utilisation of an algorithm established on ADNI data, tested in other datasets and proposed for US GAP-PAD studies to reduce screen failure based on age, cognition and APOE genotype. – Screen by PET amyloid with entry to study on a 4:1 ratio of screen positive and negative to avoid inadvertent disclosure of genotype or biomarker data – Repeated measures of both outcome comparator modalities (cognition and pathology) and assessment modalities between 2 months and 6 months in frequency based on projected one year change and acceptability criteria (see main section for full details) – Protocols harmonised with EPAD where shared and established in pilot phase for structural and functional MRI, electrophysiology by EEG and MEG, optical measures including ultra wide field studies and OCT and connected devices for gait, activity and cognition (see main section for full details) – Participant engagement including a start-up with a track record of increasing participation, a study within a study for participant engagement and burden in precision medicine studies and a process led by the Alzheimer’s Society for Patient and Public Engagement (see main section for full details) – Sharing of data with minimal delay and facilitated data-use including building analytical communities through the leading global not-for-profit organisation for scientific data sharing.
Aims
Specifically, we aim to implement PET imaging and CSF biochemistry for amyloid and tau, functional and structural MRI, electrophysiology for synaptic function including EEG and MEG, measures of gait and use of remote monitoring for ecologically valid assessment of a range of phenotypes, measures of retinal pathology and a collection of bio-samples unparalleled in potential utility for molecular biomarkers and to establish stem cells for in vitro studies. Some measures such as PET will be applied at baseline and follow up, others up to every 2 months and some, such as the peripheral devices, continuously.