Obstructive sleep apnea treatment, slow wave activity, and amyloid-β

Abstract

Obstructive sleep apnea (OSA) increases risk of dementia, a relationship that may be mediated by amyloid-β (Aβ) and downstream Alzheimer disease pathology. We previously showed that OSA may impair Aβ clearance and affect the relationship between slow wave activity (SWA) and Aβ. In this study, SWA and CSF Aβ were measured in participants with OSA before and 1 to 4 months after treatment. OSA treatment increased SWA, and SWA was significantly correlated with lower Aβ after treatment. Greater improvement in OSA was associated with greater decreases in Aβ. We propose a model whereby OSA treatment may affect both Aβ release and clearance. Ann Neurol 2018 ANN NEUROL 2019;85:291-295.

© 2018 American Neurological Association.

Figures

Figure 1 –. Association of slow wave activity and amyloid-β

Before treatment (left column), there is no significant correlation between slow wave activity as measured by delta power, and (A) Aβ40, (C) Aβ42, (E) tau, or (G) total protein in CSF. After treatment (right column), there is a significant negative correlation between SWA and (B) Aβ40 and (D) Aβ42; there is no correlation with (F) Tau or (H) total protein. Linear regression lines are shown for illustrative purposes; since the data were not normally distributed, correlations were assessed with Spearman’s correlation coefficient (r=rho) and associated p values.

Figure 2 –. Change in amyloid-βis associated with change in OSA severity.

Improvement of OSA is shown on the X-axes, with more leftward values indicating greater improvement. The graphs in the left column show change in AHI, while the graphs in the right column show change in arousals per hour. Greater improvement in OSA was associated with decreased (A,B) Aβ40, (C,D) Aβ42, and (E,F) Tau, but not (G,H) total protein. Linear regression lines are shown for illustrative purposes; since the data were not normally distributed, correlations were assessed with Spearman’s correlation coefficient (r=rho) and associated p values. (I) A schematic illustrates two interacting effects of OSA on CSF Aβ levels. With increasing arousals and sleep disruption related to OSA, SWA decreases; this leads to increased Aβ release into the interstitial space (red arrow). However, with worsening OSA severity, there is reduced glymphatic clearance from the ISF to CSF, due to abnormal pressure fluctuations during obstructive respiratory events (blue arrows). The combination of these two effects is hypothesized to result in an inverse U-shape of Aβ in the CSF with increasing OSA severity (purple curve). The black arrows illustrate the direction of change in CSF Aβ following treatment of OSA. If OSA is improved a small degree (solid black arrow), CSF Aβ levels may increase, whereas if OSA is improved a large degree (dashed black arrow), CSF Aβ may decrease.