Overview
Dementia is a leading cause of death in the UK, and long waits for diagnosis can delay access to care and treatment. The SANDBOX study is a research study in NHS Memory Clinics investigating whether providing clinicians with additional test results could help them diagnose dementia earlier.
Adults aged 50 or over who have been referred to a Memory Clinic by their GP may be invited to take part. Taking part is voluntary and will not affect a participant's care. Participation adds to their NHS care and does not replace or delay it.
Participants complete three assessments: a blood test that measures two proteins which can indicate whether Alzheimer's-related changes may be happening in the brain (not currently available on the NHS); a genetic test for the APOE gene, which influences Alzheimer's risk; and a cognitive assessment of memory and thinking that includes a recorded speech task analysed for subtle language changes. All results are shared with the participant's clinician.
This research will help determine whether this approach can support earlier dementia diagnosis and improve care for patients across the UK.
Description
The SANDBOX study evaluates an approach to integrating blood-based biomarkers, APOE4 genetic testing, and digitally administered cognitive assessments into Memory Clinic diagnostic pathways. The primary aim is to assess whether this approach improves efficiency of dementia diagnosis and patient flow through Memory Clinic services.
Participants will undergo baseline assessment including venous blood draw (42.5 mL) for analysis of plasma phosphorylated tau-217, epigenetic markers in cell-free DNA, and APOE4 genotyping. Dried blood spot samples will be collected via finger-prick.
Digital cognitive testing will be conducted using CANTAB (Cambridge Neuropsychological Test Automated Battery) and recorded speech analysis.
Blood biomarker and genetic results will be withheld from clinical teams until participants have a Memory Clinic appointment scheduled, to prevent bias in triage decisions. Results will then be shared with clinicians to support diagnostic assessment. All participants will be offered genetic counseling regarding APOE4 status.
A follow-up assessment occurs at 12 months (repeat blood draws and cognitive testing). Psychological impact of genetic disclosure will be monitored using validated questionnaires (Health Anxiety Inventory, CES-D, EQ-5D-5L, IGT-AD Scale).
Health economic analysis will evaluate cost-effectiveness of the triage system compared to standard UK practice. AI-based exploratory analyses will investigate relationships between biomarkers and dementia progression.
Eligibility
Inclusion Criteria:
- The participant is willing and able to provide informed consent for participation in the study, or if unable to consent, a consultee (nearest of kin or holder of Power of Attorney) is available to make a declaration.
- Eligibility for recruitment in Scotland is restricted to participants who are able to provide informed consent themselves; participants requiring consultee consent will not be recruited in Scotland.
- Male or female, aged 50 years or older.
- The participant is currently on a waiting list for a participating Memory Clinic.
- The participant lives within traveling distance to a study site.
- The participant agrees to complete all study procedures, including genetic testing.
Exclusion Criteria:
- The participant may not enter the study if any of the following criteria apply:
- The participant has known or anticipated challenges with venous blood sampling.
- The participant is not fluent in English.
- The participant has a historical diagnosis of dementia.
