Associations between compound heat exposure and cognitive impairment and the potential mediating role of plasma sphingolipid metabolites: Evidence from a large-scale population cohort study.

High-temperature exposure induces cognitive impairment (CI). However, large-scale population studies on the association between compound heat exposure and CI are limited, and the underlying mechanisms, especially the mediating role of sphingolipid metabolites, remain unclear. Based on the Hubei Memory and Aging Cohort Study, we repeatedly assessed 3,617 non-dementia adults aged 65 years and older at baseline from 2016 to 2025. Hourly temperatures were extracted from ERA5-Land, daily relative humidity from the China Meteorological Data Service Centre, and PM2.5 and O3 from the Tracking Air Pollution dataset. Generalized linear mixed-effects models showed that excess cumulative temperature in heatwaves (ECT-HW) was linearly associated with CI for daytime-only, nighttime-only, and day-night compound heatwaves. Temperature-humidity indicators exhibited near-U-shaped exposure-response curves, with the Humidexmean model performing best (Odds ratio = 2.18, 95% CI: 1.31-3.64). All seven indicators except ECT-HW for nighttime and compound heatwaves showed significant time interactions. These indicators were ECT-HW for daytime heatwaves, Humidexmin, Humidexmax, Humidexmean, wet bulb globe temperature (WBGT)min, WBGTmean, and WBGTmax. Among 77 plasma sphingolipid metabolites and ratios, the ratio of ceramide C22:0 to sphingomyelin C26:0 mediated the Humidexmean-CI association (proportion mediated = -14.3%). Overall, compound heat exposure was consistently associated with CI, and sphingolipid metabolites may play a potential suppression role in this association.