Predicting future dementia from routine clinical MRI and linked healthcare data
BACKGROUND: Early identification of individuals at risk of dementia is essential for preventive care and timely enrolment into disease-modifying interventions. However, most existing prediction approaches rely on invasive, costly, or research-only biomarkers that are not scalable within public healthcare systems. Routinely acquired National Health Service (NHS) brain magnetic resonance imaging (MRI) scans, when linked with electronic health records, represent a widely available and privacy-preserving resource for population-level dementia risk stratification. A key challenge for clinical translation is ensuring that machine-learning predictions are reliable, interpretable, and safe to apply, particularly when models are used years before clinical diagnosis. METHODS: We conducted a retrospective case-control study entirely within a secure NHS Trusted Research Environment using routine T1-weighted brain MRI scans linked to electronic health records from Tayside and Fife, Scotland. The study included 518 participants: 259 individuals who subsequently developed dementia and 259 age- and sex-matched controls. Structural brain features were derived from MRI data and analysed using a support-vector-machine classifier with nested cross-validation to minimise overfitting. Prediction confidence was quantified using distance-from-hyperplane (DFH) calibration, enabling stratification of model outputs by certainty. Primary outcomes were classification accuracy and area under the receiver-operating-characteristic curve (AUC). Secondary analyses examined DFH-stratified performance and the relationship between prediction accuracy and time from scan to first recorded dementia diagnosis. RESULTS: The model predicted future dementia up to five years before first recorded NHS diagnosis with an AUC of 0.71, a performance consistent with real-world clinical imaging rather than research-optimised datasets. Model sensitivity increased for scans acquired closer to diagnosis, indicating stronger predictive signal as disease onset approached. Confidence-based stratification identified a high-confidence subgroup comprising approximately 35% of scans, within which prediction accuracy increased to around 80%. Performance was consistent across heterogeneous routine NHS scanners and imaging protocols, demonstrating robustness and generalisability to real-world clinical data rather than research-optimised acquisitions. CONCLUSION: Routinely collected NHS brain MRI data can be used to predict future dementia several years before clinical diagnosis. Incorporating confidence calibration transforms a conventional machine-learning classifier into a safety-aware and clinically interpretable framework by enabling selective use of high-certainty predictions. This approach supports scalable early detection, population-level risk stratification, and targeted recruitment into preventive or disease-modifying clinical trials, with clear potential for integration into public health systems.
Authors
- Parminder Singh Reel (ORCID: https://orcid.org/0000-0001-7796-1457)
- Esma Mansouri-Benssassi (ORCID: https://orcid.org/0000-0003-3510-8129)
- Szabolcs Suveges (ORCID: https://orcid.org/0000-0003-3636-6509)
- Emanuele Trucco (ORCID: https://orcid.org/0000-0002-5055-0794)
- Salim Al‐Wasity (ORCID: https://orcid.org/0000-0002-9134-1374)
- Craig Edwards
- Smarti Reel (ORCID: https://orcid.org/0000-0002-6092-9175)
- Alexander Doney
- J. Douglas Steele
- Muthu Rama Krishnan; id_orcid 0000-0001-6437-1482 Mookiah
- Emily; id_orcid 0000-0003-2992-7582 Jefferson
- Susan Krueger
Institutions
- University of Dundee (GB)
- University of Wasit (IQ)
- Health Data Research UK (GB)
- Genomics (United Kingdom) (GB)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2026-05-21
- DOI
- https://doi.org/10.1186/s13195-026-02079-4
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Medical Research Council