Targeting Slow Wave Sleep Deficiency in Late-Life Depression: A Case Series With Propofol.

Slow wave sleep (SWS), characterized by large electroencephalographic oscillations, facilitates crucial physiologic processes that maintain synaptic plasticity and overall brain health. Deficiency in older adults is associated with depression and cognitive dysfunction, such that enhancing sleep slow waves has emerged as a promising target for novel therapies. Enhancement of SWS has been noted after infusions of propofol, a commonly used anesthetic that induces electroencephalographic patterns resembling non-rapid eye movement sleep. This paper 1) reviews the scientific premise underlying the hypothesis that sleep slow waves are a novel therapeutic target for improving cognitive and psychiatric outcomes in older adults, and 2) presents a case series of two patients with late-life depression who each received two propofol infusions. One participant, a 71-year-old woman, had a mean of 2.8 minutes of evening SWS prior to infusions (0.7% of total sleep time). SWS increased on the night after each infusion, to 12.5 minutes (5.3% of total sleep time) and 24 minutes (10.6% of total sleep time), respectively. Her depression symptoms improved, reflected by a reduction in her Montgomery-Asberg Depression Rating Scale (MADRS) score from 26 to 7. In contrast, the other participant, a 77-year-old man, exhibited no SWS at baseline and only modest enhancement after the second infusion (3 minutes, 1.3% of total sleep time). His MADRS score increased from 13 to 19, indicating a lack of improvement in his depression. These cases provide proof-of-concept that propofol can enhance SWS and improve depression for some individuals, motivating an ongoing clinical trial (ClinicalTrials.gov NCT04680910).

Awareness with Recall: Review and Guide to Electroencephalographic Depth-of-Anesthesia Monitoring.

Awareness with recall is an uncommon but potentially devastating neurological complication following perioperative care. End-tidal anesthetic gas concentration alarms can supplement usual care to reduce risk. Processed electroencephalographic (EEG) measures provided by depth-of-anesthesia monitors may be helpful, particularly for high-risk patients. Interpretation of EEG waveforms may supplement these processed EEG metrics to minimize risk of awareness with recall.

Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults.

Background: The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states. Methods: In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation. Results: Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of -17.1 min, 95% confidence interval -30.0 to -8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=-0.61, P=0.03). Conclusions: Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults. Clinical trial registration: ClinicalTrials.gov NCT04206059.