Abstract Introduction Associations between sleep architecture and change in plasma amyloid biomarkers have been only minimally evaluated, despite their advantages of high accessibility and safety when sampling. Here we examined the longitudinal effect of REM sleep on plasma beta-amyloid (Aβ) 42/40 ratio in cognitively normal older adults. Methods Sixty-four community-dwelling cognitively normal adults ages 55 to 90 were recruited at the NYU Alzheimer’s disease research center. All participants completed a baseline polysomnogram and had repeated plasma collections 3.2 ± 2.0 years apart. Plasma Aβ 42 and 40 were measured via mass spectrometry (Araclon Biotech, Spain). Amyloid positivity was calculated with the Youden Index (Aβ 42/40 ratio ≤0.0992). We evaluated associations between %REM sleep and annualized changes in the plasma biomarker divided by year interval (Δ Aβ42/40Post-Pre / year interval) using bivariate Spearman’s correlation and generalized linear models with annualized changes in the plasma biomarker divided by year interval (Δ Aβ42/40Post-Pre / year interval) as the dependent variable, after adjusting for age, sex, apolipoprotein ε4 (APOE4) status, presence of OSA (AHI4% ≥ 5/hour), and the use of SSRI/SNRI’s. Results Subjects were 66.7 ± 7.4 years old, 68.5% female, 57.4% Caucasian, 38.9 % APOE4 carriers, 18.5% amyloid positive, 46.3% with Apnea-Hypopnea Index 4% (AHI4%) ≥5, and 3.1% with SSRI/SNRI use. Total sleep time was 366.5 ± 83.3 minutes, REM sleep duration was 72.6 ± 31.1 minutes, and the percentage of REM sleep of total sleep time (REM%) was 19.4 ± 6.4%. Low REM% was significantly correlated with a high annual decline of plasma Aβ42/40 ratio (ρ=0.31, p=0.013), though to reflect increased intracranial amyloid, and was associated with an annual decline of plasma Aβ42/40 ratio, after adjusting for covariates (β=2.08, p=0.043). In a subgroup analysis, low REM% was significantly associated with a high annual decline of plasma Aβ42/40 ratio in the Aβ positive group (β=3.20, p=0.033), but more weakly so in the negative group (β=1.52, p=0.14). Conclusion A low percentage of REM sleep might be an indicator of a faster accumulation of intracranial amyloid in cognitively normal older adults. This relationship was more strongly observed once amyloid pathology initiates, even before cognitive symptom onset. Support (if any)
Hwang et al. (Fri,) studied this question.