American Journal of Respiratory and Critical Care Medicine · May 2026
A80-1-02 Longitudinal Effect of Sleep Apnea Burdens on Plasma Alzheimer’s Disease Biomarker in Cognitively Normal Older Adults
By Hwang J, Atilano LF, Boulgakov P et al.
Abstract Introduction Obstructive Sleep Apnea (OSA) is common in the elderly, and may accelerate amyloid accumulation in the brain. To assess OSA’s potential mechanistic contributions, we explored longitudinal effects of sleep apnea burdens on the plasma beta-amyloid (Aβ) 42/40 ratio in cognitively normal older adults. Methods Sixty-four community-dwelling cognitively normal adults aged between 55 and 90, with Mini-Mental State Exam scores of 25 or more, were recruited at New York University’s Alzheimer’s Disease Research Center. All participants completed a baseline polysomnogram and had repeated plasma collections at least two years apart (3.16 ± 1.96 years). Subjects remained untreated for any incidentally identified OSA. Plasma Aβ 42 and 40 were measured via mass spectrometry (Araclon Biotech, Spain). We evaluated associations between each sleep apnea burden and annualized plasma biomarker changes (Δ Aβ42/40Post-Pre / year interval) using bivariate Spearman correlations and general linear models (GLM) controlling for age, sex, and apolipoprotein ε4 (ApoE4) genotype status. Hypoxic burden was defined as 1) the duration of time spent with an oxygen saturation below 90% (T90) and 2) the area under the SpO2 curve (HB-AUC). The ventilatory burden (VB) is defined as the percentage of overnight breaths with <50% amplitude from the overnight ventilatory distribution. The arousal index (AI) is calculated as the total number of arousals normalized to total sleep time. Results Subjects were 66.67 ± 7.40 years old, 68.5% female, 57.4% Caucasian, 38.9 % ApoE4 positive, 18.5% baseline Aβ 42/40 ratio positive, 53.7% with Apnea-Hypopnea Index 4% (AHI4%) <5, 26.0% with AHI4% 5-15, and 20.3% with AHI4% ≥15. AHI4%, AHI3A, T90, HB-AUC, VB, and AI were not significantly correlated with annualized plasma Aβ42/40 ratio at the bivariate level or in the GLM. High AI was significantly correlated with a large annual decline in plasma Aβ42/40 ratio (reflecting increased intracranial amyloid) in the group with AHI4% <5 (ρ=-0.398, p = 0.045) at the bivariate level, but this association did not persist in the GLM. No bivariate correlation with AI was observed in the group with AHI4% ≥5 (ρ=-0.236, p = 0.235). Conclusion We did not observe significant influences of hypoxic or ventilatory burden on plasma amyloid changes, but this may have been limited by the small number of participants with moderate to severe sleep apnea in this study population. The bivariate correlation between arousal index and longitudinal amyloid changes via plasma biomarker in subjects without OSA may be worth exploring in a larger population of older adults without OSA. This abstract is funded by: None