Brain Health from Sleep EEG: A Multicohort, Deep Learning Biomarker for Cognition, Disease, and Mortality.

Ganglberger, Wolfgang; Sun, Haoqi; Turley, Niels; Tripathi, Ayush; Hadar, Peter; Gupta, Aditya; Gallagher, Kaileigh; Tesh, Ryan et al. · NEJM AI · 2026

prospective_cohort · Level II

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Abstract

Sleep underpins cognition, disease prevention, and overall brain health, yet objective, integrative biomarkers of brain health remain lacking. We hypothesized that overnight sleep electroencephalography (EEG) could provide a substrate for such a biomarker. We asked whether a newly developed, end-to-end, data-driven deep learning framework for sleep EEG can learn a latent representation of brain health and distill it into a single score relevant to cognition, disease status, and mortality. We analyzed 36,000 polysomnography recordings from 27,000 subjects from six cohorts. EEG data were represented as one-dimensional time series or a two-dimensional time-frequency spectrogram. A multitask deep neural network, trained end-to-end without expert-defined features, learned a 1024-dimensional brain health latent space and jointly predicted cognitive performance, disease status, and sleep metrics. The latent representation was additionally distilled into a single brain health score. We compared performance with demographic baselines, conventional EEG metrics (e.g., rapid eye movement fraction, spindle density), and classic multivariate machine learning approaches. The deep learning-derived brain health scores consistently surpassed demographic and expert-defined EEG feature models. For cognitive outcomes, correlations (r) rose from small (demographic-only) to moderate (up to r=0.40), while disease classification areas under the receiver operator curve improved from 0.50-0.55 at baseline to 0.65-0.75. In age-adjusted Cox models, a one-standard-deviation increase in the brain health score was associated with a 31%-35% reduced risk of mortality (hazard ratio 0.65 to 0.69; P<0.0001), topping conventional EEG metrics. Gains over classic machine learning, plus latent space visualization, indicated that both established physiological markers and novel EEG features drove enhanced performance. A multitask, end-to-end deep learning approach generated an interpretable, sleep-derived brain health biomarker. By modeling cognition, disease, and mortality, this framework provides a robust index of brain health and may be extended to additional modalities, further enhancing its clinical utility. (Funded by the National Institutes of Health and others.).