# Machine Learning–Based Sleep Electroencephalographic Brain Age Index and Dementia Risk: An Individual Participant Data Meta-Analysis

**Authors:** Haoqi Sun, Sasha Milton, Yi Fang, Hash Brown Taha, Shreya Shiju, Robert J. Thomas, Wolfgang Ganglberger, Matthew P. Pase, Timothy Hughes, Shaun Purcell, Susan Redline, Katie L. Stone, Kristine Yaffe, M. Brandon Westover, Yue Leng

PMC · DOI: 10.1001/jamanetworkopen.2026.1521 · 2026-03-19

## TL;DR

A machine learning model using sleep EEG data can predict dementia risk, with higher brain age index linked to a 39% increased risk.

## Contribution

Introduces a machine learning–based sleep EEG brain age index as a novel digital marker for dementia risk.

## Key findings

- Each 10-year increase in BAI was associated with a 39% higher dementia risk after adjusting for age, sex, and other factors.
- The association remained significant after adjusting for comorbidities and apnea-hypopnea index scores.
- Findings were consistent across sex and age groups, suggesting broad applicability.

## Abstract

Is a higher brain age index (BAI) derived from sleep electroencephalography (EEG) using machine learning associated with a higher risk of future dementia in community-dwelling older adults?

In this individual participant data meta-analysis of 7105 adults from 5 longitudinal cohorts, every 10-year increase in BAI was associated with a 39% higher risk of incident dementia, independent of age, sex, apolipoprotein E ε4 status, and global cognition and comorbidities at the sleep study.

These findings suggest that sleep EEG-based BAI may serve as a promising early digital marker for dementia risk stratification.

This individual participant data meta-analysis explores the association between a machine learning–based sleep electroencephalography (EEG) brain age index and dementia risk among community-dwelling adults from 5 longitudinal cohorts.

Microstructures of sleep electroencephalography (EEG) are closely related to cognition and undergo age-dependent changes. However, their multidimensional nature makes them challenging to interpret using conventional approaches. The machine learning–based EEG brain age index (BAI) measures the deviation between sleep EEG-based brain age and chronological age.

To determine the association between sleep BAI and incident dementia in community-dwelling populations.

For this individual participant data (IPD) meta-analysis, sleep study data from 5 community-based longitudinal cohorts were pooled. These cohorts included the Multi-Ethnic Study of Atherosclerosis (MESA; 2010-2013), the Atherosclerosis Risk in Communities (ARIC) study (1987-1989), the Framingham Heart Study–Offspring Study (FHS-OS; 1995-1998), the Osteoporotic Fractures in Men Study (MrOS; 2003-2005), and the Study of Osteoporotic Fractures (SOF; 2002-2004).

Adults (aged ≥18 years) without dementia at the time of polysomnography were included.

The BAI was computed using interpretable machine learning, incorporating sleep EEG features extracted from central channels in overnight, home-based polysomnography. Fine-Gray models were used to assess the association between BAI and incident dementia within each cohort, accounting for death as a competing risk. Cohort-specific estimates were then pooled using random-effects meta-analysis. Analyses were performed between March 2024 and September 2025.

Incident dementia or probable dementia was determined in each cohort, with death as a competing risk.

This meta-analysis included 7105 participants from the MESA (n = 1802; mean [SD] age, 69.3 [9.0] years; 956 females [53.1%]), ARIC (n = 1796; 62.5 [5.7] years; 918 females [51.1%]), FHS-OS (n = 617; 59.5 [8.9] years; 318 females [51.5%]), MrOS (n = 2639 males [100%]; 76.0 [5.3] years), and SOF (n = 251 females [100%]; 82.7 [2.9] years) cohorts. The median (IQR) time to dementia was 4.8 (4.2-5.6) years in the MESA cohort (n = 119 [6.6%]), 16.9 (14.9-19.8) years in the ARIC cohort (n = 354 [19.7%]), 13.1 (8.5-16.2) years in the FHS-OS cohort (n = 59 [9.6%]), 3.6 (1.3-7.1) years in the MrOS cohort (n = 470 [17.8%]), and 4.6 (4.2-5.2) years in the SOF cohort (n = 86 [34.3%]). Across the cohorts, each 10-year increase in BAI was associated with a 39% higher risk of incident dementia (hazard ratio [HR], 1.39 [95% CI, 1.21-1.59]; P < .001) after adjustment for covariates. These associations remained after additional adjustment for comorbidities and apnea-hypopnea index scores (HR, 1.31 [95% CI, 1.14-1.50]; P < .001) and apolipoprotein E ε4 (HR, 1.22 [95% CI, 1.02-1.45]; P = .03), and they were consistent across sex and age groups.

In this IPD meta-analysis, a higher sleep EEG-based BAI was associated with a higher risk of incident dementia. These findings highlight the need to evaluate the predictive value of the BAI as a noninvasive digital marker for early detection of dementia in community settings.

## Linked entities

- **Diseases:** dementia (MONDO:0001627)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}
- **Diseases:** neurodegenerative diseases (MESH:D019636), diabetes (MESH:D003920), ARIC (MESH:D050197), OS (MESH:C567932), cognitive decline (MESH:D003072), Sleep disturbances (MESH:D012893), Mental Disorders (MESH:D001523), Osteoporotic Fractures (MESH:D058866), death (MESH:D003643), depression (MESH:D003866), epilepsy (MESH:D004827), stroke (MESH:D020521), Apnea (MESH:D001049), degeneration of the thalamus (MESH:D009410), AD (MESH:D000544), amyloid (MESH:C000718787), hypertension (MESH:D006973), BAI (MESH:D001927), hypopnea (MESH:D012891), Dementia (MESH:D003704), myocardial infarction (MESH:D009203)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13003368/full.md

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Source: https://tomesphere.com/paper/PMC13003368