REAl World Dementia OUTcomes: Observational Study (READ-OUT)

READ-OUT - REAl World Dementia OUTcomes: Observational Study

READ-OUT observational study will investigate blood-based biomarkers for dementia in real-world clinical settings. This 3-year observational study will include 3165 people, males or females aged 45 years or older, with cognitive impairment of any severity.

Participants provide blood samples and complete questionnaires about quality of life and healthcare use, with some having additional follow-ups at 2 weeks and 1 year. The study will assess reliability and accuracy of blood tests in diagnosing dementia.

Study Overview

• Status: Enrolling by invitation
• Conditions: Dementia; Mild Cognitive Impairment (MCI); Alzheimer Disease (AD)

Detailed Description

Dementia affects a growing number of people in the UK, with significant costs for individuals, families, and society. There is an urgent need for accurate diagnosis of dementia to allow early intervention and support when people can still make decisions about their care.

Current dementia diagnosis in memory clinics relies on clinical assessment, cognitive testing, and brain scans (MRI or CT). Only a small proportion of UK patients have access to more specific tests like PET brain scans or spinal fluid analysis, which are expensive and not widely available.

Recent developments have shown that blood tests can accurately detect the underlying brain changes of dementia, particularly Alzheimer's disease. In research studies, these blood-based biomarkers (ptau217, AB42/40 ratio, GFAP, NFL etc) have successfully identified people with Alzheimer's disease when compared to clinical diagnoses, gold standard brain scans, and post-mortem brain examination. These blood tests also show promise for predicting people with future dementia risk.

However, most research has been conducted in younger, less diverse populations than those seen in real-world memory services. Blood-based biomarkers are not yet used in routine NHS practice, and more work is needed to test how well they perform in representative UK populations. We also need to understand whether people want to know their blood test results, what information they want, and how this is best communicated.

The READ-OUT study will test blood-based biomarkers in people attending memory clinics across the UK (30 NHS sites), ensuring participants represent the full diversity of people with dementia or memory concerns (30% from underrepresented groups). Participants will provide a 40ml blood sample and complete questionnaires about quality of life, healthcare use, and attitudes toward blood testing for dementia. The accuracy of blood biomarkers will be compared against established diagnostic methods including expert clinical review, brain scans, spinal fluid tests, and long-term health record follow-up.

The study includes three optional sub-studies: test-retest reliability of blood biomarkers (10% of participants returning after 1-2 weeks), investigating disease progression over one year (20% of participants), and evaluating whether people can collect blood samples at home using finger-prick cards (75 participants).

The study will determine which blood biomarkers are most accurate for diagnosing different types of dementia, predict disease progression, and assess their cost-effectiveness in the healthcare system. Results will inform whether these tests should be integrated into NHS clinical pathways and will guide the design of READ-OUT Phase 2, a randomized trial testing whether providing blood biomarker results to patients and doctors improves clinical care and outcomes.

• Study Type: Observational
• Enrollment (Estimated): 3165

Contacts and Locations

Study Locations

• United Kingdom
  • Bangor, United Kingdom
    • Betsi Cadwaladr University Health Board
  • Bath, United Kingdom
    • ReMind UK
  • Belfast, United Kingdom
    • Belfast Health & Social care Trust
  • Bournemouth, United Kingdom
    • Dorset Healthcare University NHS Foundation Trust
  • Bracknell, United Kingdom
    • Berkshire Healthcare NHS Foundation Trust
  • Bradford, United Kingdom
    • Bradford District Care NHS Foundation Trust
  • Bristol, United Kingdom
    • North Bristol NHS Trust
  • Cambridge, United Kingdom
    • Cambridgeshire and Peterborough NHS Foundation Trust
  • Exeter, United Kingdom
    • Devon Partnership NHS Trust
  • London, United Kingdom
    • St George's Hospital
  • London, United Kingdom
    • Barts Health NHS Trust
  • London, United Kingdom
    • West London NHS Trust
  • London, United Kingdom
    • East London NHS Foundation Trust
  • London, United Kingdom
    • South London and Maudsley (SLaM)
  • Manchester, United Kingdom
    • Greater Manchester Mental Health Foundation Trust
  • Newcastle upon Tyne, United Kingdom
    • Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust
  • Newport, United Kingdom
    • Aneurin Bevan University Health Board
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust
  • Oxford, United Kingdom
    • Oxford Health NHS Trust
  • Preston, United Kingdom
    • Lancashire & South Cumbria NHS Foundation Trust
  • Redhill, United Kingdom
    • Surrey and Borders Partnership NHS Foundation Trust
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospital
  • Sheffield, United Kingdom
    • Sheffield Health and Social Care NHS Foundation Trust
  • Southampton, United Kingdom
    • University Hospital Southampton
  • Southampton, United Kingdom
    • Hampshire and Isle of Wight NHS Foundation Trust
  • Stafford, United Kingdom
    • Midlands Partnership University NHS Foundation Trust
  • Worthing, United Kingdom
    • Sussex Partnership NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People referred to, eligible for referral or already under review at primary and/or secondary memory assessment services (including memory clinics, brain health clinics) with some form of cognitive symptoms and/or cognitive disorders of any severity will be eligible for recruitment. Also, we recruit a subset of individuals who are not under a secondary care memory clinic but who have a clinical picture that would be suitable for secondary care assessment in memory clinic services.

Description

Inclusion Criteria:

The participant may enter the study if ALL of the following apply:

• Willing and able to give informed consent for participation in the study (translation needs for study information and forms for non-English speakers will be defined locally) OR Adults who otherwise lack the capacity to consent but for whom advice regarding participation has been obtained via a consultee using the personal or nominated consultee process
• Male or Female, aged 45 years and above
• Referred or referable with cognitive or behavioural symptoms and/or diagnosed with a cognition related disorder; including those with subjective cognitive impairment and functional disorders.

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

• Lack of venous access
• Unwilling to consent to NHS data linkage or in Northern Ireland, unwilling to allow long term follow up by access to electronic NHS records.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of blood-based biomarkers for dementia diagnosis	Accuracy, Positive and Negative predictive value in regard to diagnosis and, where available, gold standard biomarker measures (clinical consensus, cerebrospinal fluid, CSF, positron emission tomography, PET)	baseline and at 52 weeks
Feasibility and acceptability of blood-based biomarkers for dementia diagnosis	Recruitment metrics at site level Acceptability patient questionnaires Patient and Public Involvement qualitative data around acceptability of BBM collection	baseline, at 2 weeks and 52 weeks
Cost-effectiveness of blood biomarkers in a real-world cognitive disorders population	Health-related quality of life (HR-QoL) Healthcare utilisation	baseline and at 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease prediction utility of blood-based biomarkers in diverse cognitive disorders populations	Cognitive score progression, MCI to dementia conversion, Institutionalisation, or Death, ethnicity.	baseline and at 52 weeks
Optimal individual or sets of biomarkers for separate dementia aetiologies	Accuracy, Positive and Negative predictive value in regard to subgroups of dementia diagnosis	baseline, at 2 weeks and 52 weeks
Impact of sample processing delays on the accuracy of blood biomarkers	BBM levels obtained from samples of varying degrees of processing delays	Baseline study visit
The test-retest reliability of blood biomarkers	BBM levels obtained from repeated sampling at baseline and after 1-2 week - a sub- study involving 10% of the participant sample. Whether samples taken at different time points are comparable will be assessed	Baseline study visit, 1-2 week visit
The utility of remote blood test kits	Comparison of BBM levels obtained from phlebotomy and blood spot cards/Capillary Tubes involving 75 individuals within the sample; Accuracy, positive and negative predictive value for blood spot card/Capillary Tubes BBMs	Baseline study visit
Understanding participant preferences on disclosure of biomarker status in dementia diagnosis	Evaluation of participants' views on what information they wish to receive about their biomarker status, the preferred timing of disclosure, and the most appropriate method of communication. Quantitative data will be collected via questionnaires completed by all participants at baseline. A qualitative sub-study involving 15-20 participants, supported by the trial PPIE group, will explore experiences and preferences in greater depth through interviews and/or focus groups.	baseline and at 52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analysis to support development of novel multi-omics assays for dementia diagnosis and prognosis	Exploratory analyses will focus on identifying and validating potential diagnostic or prognostic biomarkers through multi-omics approaches	baseline and at 52 weeks

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Imperial College London; University College, London; Queen's University, Belfast; Queen Mary University of London; University of Bristol; University of Edinburgh; University of Cambridge; Aneurin Bevan University Health Board; Greater Manchester Mental Health NHS Foundation Trust; West London NHS Trust
• Investigators: Principal Investigator: Vanessa Raymont, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: September 1, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Dementia; Diagnosis; Cognitive impairment; Blood-based biomarkers; memory clinics
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Disease; Dementia
• Other Study ID Numbers: 24/WA/0330; ARUK-BBC2023-001 (Other Grant/Funding Number: Alzheimer's Research UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised (linked) BBM and genetic data will be available for access (not copying/export) via the DPUK Data Portal (https://portal.dementiasplatform.uk/) upon an approved data/sample access proposal. It offers a secure, fully auditable data repository (currently facilitating access to data for over 3.6m individuals across more than 60 cohorts). A curated (standardised/harmonised) dataset will be made available to eligible researchers within the DPUK Trusted Research Environment (TRE) which is at the core of the Data Portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No