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

Abstract

Importance 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. Objective To determine the association between sleep BAI and incident dementia in community-dwelling populations. Data Sources 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). Study Selection Adults (aged ≥18 years) without dementia at the time of polysomnography were included. Data Extraction and Synthesis 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. Main Outcomes and Measures Incident dementia or probable dementia was determined in each cohort, with death as a competing risk. Results 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