JMIR Publications

ABSTRACT

Background:

Dementia is a growing global burden; however, scalable, low-cost strategies for early risk identification are lacking. Because cardiac and cognitive aging are closely associated, a routinely collected 12-lead electrocardiogram (ECG), interpreted using foundation-model embeddings, is a promising and accessible candidate marker. Whether such embeddings carry predictive information independent of chronological age, the dominant risk factor for dementia, and whether the underlying changes follow a detectable pre-diagnostic trajectory remain unknown.

Objective:

We investigated whether foundation-model embeddings of routine ECGs carry information about incident cognitive impairment and dementia beyond chronological age and, if so, whether the underlying ECG changes intensify as the time of diagnosis approaches.

Methods:

In a retrospective two-site Korean cohort (Severance, development n=52,355; Yongin Severance, external n=6,500), embeddings from the knowledge-enhanced diagnosis foundation model supported an ECG-only classifier for 10-year incident cognitive impairment and dementia, using only ECGs interpreted as normal sinus rhythm. We compared an age-only model with a late fusion of age and ECG-derived probability and tested whether age-residualized embedding remained predictive as direct evidence of age-independent information. Discrimination was summarized by the area under the receiver operating characteristic curve (AUROC) with 95% bootstrap CIs, and DeLong tests and net reclassification improvement (NRI) were used for between-model comparisons. To trace the pre-diagnostic time course, we analyzed ECG phenotype labels across four windows before diagnosis in an exact-age-matched case–control set.

Results:

Chronological age discriminated strongly (external AUROC 0.809, 95% CI 0.799–0.819), and adding ECG-derived probability improved discrimination, calibration, and net benefit over age alone (external AUROC 0.825, 95% CI 0.816–0.834; DeLong P<.001; positive NRI). Critically, even after removing the age-predictable component, age-residualized embedding retained modest but reproducible discrimination in both internal (AUROC 0.590, 95% CI 0.581–0.599) and external (AUROC 0.579, 95% CI 0.567–0.592) validation (both P<.001), indicating dementia-relevant information that was not explained by chronological age. Of the 105 ECG labels, 19 showed a case–control difference that widened significantly toward diagnosis, dominated by nonspecific ST-segment and T-wave changes, acute ischemic patterns (acute myocardial infarction), and atrial and junctional arrhythmias (atrial flutter, ectopic atrial, and accelerated junctional rhythms), with divergence emerging mainly in the proximal (1–3 year) and imminent (0–1 year) windows.

Conclusions:

Routine-ECG foundation-model embeddings encode aging-related electrophysiological information that is complementary to and not fully explained by chronological age and intensifies as diagnosis approaches through ischemic and arrhythmic changes. These findings suggest that routine ECG is a low-cost, age-complementary triage signal within the heart–brain-axis screening pathway, rather than a stand-alone diagnostic test.