Remote blood biomarker sampling to detect risk of early Alzheimer’s disease in older adults living in the community (REBEL)

Research question What is the predictive validity of remotely collected blood biomarkers alone and in combination with computerised neuropsychology, in detecting risk of dementia, and how can these technologies be integrated into healthcare for patient benefit? Background There is an urgent need to improve early detection of neurodegeneration to improve early access to emerging treatments, enable individuals to reduce their dementia risk and improve the clinical pathway to early diagnosis. Blood biomarkers ptau217, GFAP and NfL have robust evidence supporting their use as markers of Alzheimer s Disease and neurodegeneration, including other dementia sub-types. New technologies are now emerging for at-home finger-prick blood testing to enable remote biomarker assessment. Computerised cognitive assessment also offers a means of identifying pre-clinical cognitive change. In combination, these technologies offer a means of detecting dementia and at-risk groups in the community, at scale. To realise this potential patient benefit there is a need to demonstrate their predictive validity, and to establish how they could be embedded in the clinical pathway whilst ensuring patients are supported and safeguarded. Aims and Objectives To deliver a clinical investigation of the combined REBEL technology of remote blood biomarker and neuropsychology assessment to predict risk of dementia. To conduct stakeholder consultation and a pilot study to explore how the technologies could be best positioned in the NHS and how dementia risk should be responsibly communicated to patients. Methods Workpackage 1 will deliver a clinical investigation in 1250 adults over 60 with early cognitive impairment, recruited through the PROTECT-UK cohort. Participants will be divided into high, medium and low risk groups based on baseline finger-prick blood biomarker assessment and followed up with computerised neuropsychology for 30 months. At 30 months, all high-risk and 10% of medium- and low-risk individuals will provide a follow-up blood sample. All individuals meeting criteria for conversion to dementia based on neuropsychology data will receive a Clinical Dementia Rating (CDR) assessment, and a clinical adjudication panel will confirm diagnoses. Analysis will determine the predictive accuracy of the REBEL technology for dementia risk, in addition to further analysis to characterise the medium- and low-risk patient groups. Workpackage 2 will conduct in-depth stakeholder consultations to explore how the REBEL technology could be embedded into clinical pathways, including focus groups with patients and primary/secondary care physicians. A pilot study will evaluate an optimised risk feedback model with 10 participants to establish best fit for use in real-world settings and ensure patients are safeguarded. Timelines for delivery This is a 36-month study. The clinical investigation will last 30 months, with the stakeholder consultation and pilot running in parallel in the second and third year, respectively. Anticipated Impact and Dissemination REBEL offers a scaleable, affordable risk prediction model for community-dwelling older adults, and has the potential to provide earlier, more accurate identification of patients to improve prognosis, ensure access to early treatment, and improve efficiency in the NHS. Following academic dissemination, REBEL will be communicated to professional and public audiences for rapid adoption into clinical practice and public health.