Polysomnographic Slow Wave Activity Features Are Associated with Longitudinal Global Amyloid PET Accumulation in Patients with Sleep Apnea
Diego Carvalho1, Vaclav Kremen1, Erik St. Louis1, Stuart McCarter1, Jan Bukartyk1, Scott Przybelski1, Bradley Boeve1, Ronald Petersen1, Clifford Jack1, Jonathan Graff-Radford2, Gregory Worrell3, Virend Somers1, Prashanthi Vemuri1
1Mayo Clinic, 2Neurology, Mayo Clinic, 3Mayo Clinic College of Medicine
Objective:
To assess whether polysomnographic (PSG) sleep features are associated with Amyloid-PET accumulation in patients with obstructive sleep apnea (OSA).
Background:
The relationship between sleep parameters and longitudinal amyloid accumulation in OSA remains unclear.
Design/Methods:
From the Mayo Clinic Study of Aging cohort, we identified 64 participants >=60 years old who had at least two consecutive Amyloid (PiB)-PET scans and a PSG confirming OSA (AHI≥5/hour) within 5 years of the baseline scan but before the second scan. Annualized PiB-PET accumulation (global ΔPiB/year) was estimated by the difference between the second and first log-transformed global PiB-PET estimations (SUVR) divided by the interval between scans (years). Slow-wave activity (SWA) during NREM sleep was characterized by the mean % relative contribution in slow oscillation (SO) (0.5-0.9 Hz) and delta (1-3.9 Hz) frequency bands, and by their slopes in both frequency ranges (SO-slopes and delta-slope). We fit linear regression models to test for associations between global ΔPiB/year, apnea severity markers and SWA features (mean SO% and delta% or mean SO-slope and delta-slope), after adjusting for age at baseline PiB-PET, APOE4, interval between scans, and baseline amyloid positivity.
Results:
Participants’ mean age=72.8 ± 7.7 years at baseline; 62.5% male; 93.8% cognitively unimpaired. For 1 s.d. increase in SO% and SO-slope, global ΔPiB/year increased by 0.003375 (95% CI 0.000245;0.006505, p=0.035) and 0.006182 (95% CI: 0.001337; 0.011027, p=0.013), which were comparable to 31% and 50% of the effect size associated with baseline amyloid positivity, respectively. Delta-slope was associated with a reduction in global ΔPiB/year by -0.005893 (95% CI: -0.010681; -0.001105, p=0.017). Sleep apnea severity was not associated with global ΔPiB/year.
Conclusions:
Although SO has been implicated in the clearance of amyloid, SO and their slopes also represent increased homeostatic sleep pressure. Increased SO% and SO-slopes in sleep apnea may signal chronically poorer/insufficient sleep, potentially contributing to longitudinal amyloid accumulation.