It is time again for a post about highlights from our annual sleep apnea and snoring course. This year, we had over 200 in attendance, and I learned so much from colleagues. I always focus on nonsurgical topics because this course uniquely combines surgical and nonsurgical content, with the nonsurgical talks often including information that is newer to me. Below I discuss information that was new to me and, in some cases, information that is so important that it is worth repeating.

Neurologist Liza Ashbrook, MD from UCSF spoke about sleep disorders and dementia. I have written previously about the association between dementia and a wide range of sleep disorders: untreated moderate to severe obstructive sleep apnea (OSA); short sleep (less than 6 hours of sleep), and sleep fragmentation (disrupted sleep). As the years pass, more research is showing us how this occurs, as sleep disorders interfere with normal function of the glymphatic system that clears out waste products (tau, alpha-synuclein, beta-amyloid) from the brain. These waste products form normally in the brain during daily activity, and the accumulation of them has been identified as a cause of multiple neurodegenerative disorders.

Sleep neurologists provide unique insight into management of sleep disorders, and Dr. Ashbrook later gave an interesting talk about antihistamines. While diphenhydramine (commonly found in Benadryl) is used by many patients, it has important side effects of drowsiness because it works on many receptors besides histamine receptors. She showed that doxepin at low doses (3-6 mg) may have benefit in improving sleep for insomnia patients because studies show that it is improves sleep efficiency (the proportion of time in bed actually sleeping) and amount of REM sleep without leaving patients sedated after awakening. This occurs because doxepin is selective for H1 (histamine) receptors than other medications. The effects are greater later in the night, as this is the time that histamine levels in the brain (promoting awakening) start increasing.

Megan Durr, MD from UCSF spoke about OSA in women. She spoke about the important fact that OSA is much more common in women than is commonly reported, with substantial underdiagnosis in women. This is particularly important because OSA in women often develops during pregnancy and menopause. In pregnancy, OSA affects approximately 27% of women in the third trimester, when OSA is associated with increased risks to the mother and fetus. She also spoke about how women have a different combination of symptoms than men: fatigue, insomnia/fragmented sleep, depression or anxiety, and mental fogginess. The last critical point she made is that women are less-likely to have 4% drops in oxygen levels with OSA events, contributing to underdiagnosis when using this criteria for scoring sleep studies.

Atul Malhotra, MD from UCSD spoke about the challenges of using the apnea-hypopnea index (AHI) or other metrics to measure the severity of OSA. He spoke about the different definitions of hypopneas as well as the fact that AHI cannot be expected to reflect all the potential consequences of OSA. Hypoxic burden is another measure of OSA severity, incorporating the degree and duration of drops in oxygen levels. It has been associated with mortality risk, but there are other studies showing that it might not be clearly associated with health outcomes. Importantly, he presented research showing that sleep fragmentation (disruption of sleep) may be equally important to drops in oxygen levels, especially for cognitive function (memory consolidation) and daytime function (sleepiness).

A later talk from Dr. Malhotra related to OSA and cancer risk showed studies that indicate that the sleep fragmentation and intermittent hypoxia (low oxygen levels) may both be important in increasing cancer risk as they contribute to cancer growth and metastasis. Most of the work looking at specific reasons for the association between OSA and cancer has been done in animals (often mice). Future research in humans will go a long way to understanding whether the increased cancer risk is seen only in solid tumors and the specific features of OSA that may be causing this increased risk.

Diana Thiara, MD, an obesity medicine specialist at UCSF, discussed weight loss approaches that can be so helpful in OSA. She emphasized that improved nutrition, physical activity, and behavioral therapy are the cornerstones of weight loss, adding that these also can be invaluable in reducing the side effects of other weight-loss strategies. Activity recommendations are at least 150 minutes of moderate intensity aerobic activity, in addition to strength training at least twice a week.

She also discussed semaglutide/Wegovy (GLP-1 medication) and tirzepatide/ZEPBOUND (combination GIP/GLP-1 medication) that are currently approved for weight loss. GLP-1 medications work by decreasing gastric emptying, promoting satiety (feeling full in the stomach), increasing insulin secretion, and increasing insulin sensitivity. GIP has the added benefit of increasing lipolysis and fatty acid synthesis. although the combination medications have greater associated weight loss, on average, it is important to note that the dose of the GLP-1 medication in the combinations is generally lower, so the benefits of the combination is not always greater than GLP-1 medications alone. Interestingly, women achieved greater weight loss (by percentage) in the SURMOUNT-OSA study. She also discussed the development of retatrutide, a combination medication that adds a third component: a glucagon receptor agonist to increase lipolysis and energy expenditure; she pointed out that a Phase 2 trial provided encouraging results but that this is not FDA-approved and should not be used by patients.Phase 3 trials of retatrutide (TRIUMPH 1-4) should have results available later this year.

Edward Weaver, MD, MPH from the University of Washington shared insights on a number of recent publications and hot topics in sleep apnea. Among these, he highlighted a Korean study showing that OSA was associated with disruption of the glymphatic system (both at the start of the study and over a 4-year period) and that this disruption was associated with worsening of cognitive function. Another study examined a study led by Constance Fung, MD, MSHS from UCLA, showing that adding a wearable device to measure oxygen levels in the bloodstream during CPAP use can improve CPAP use and provide information (oxygen levels) to ensure that patients are being treated appropriately.

Nalaka Gooneratne, MD, MSc from the University of Pennsylvania spoke about insomnia, including the combination of insomnia and OSA (COMISA). He emphasized the fact that wearable devices can provide useful information on sleep duration (they are less-accurate for measuring sleep staging). Obtaining data on sleep duration can allow healthcare providers to distinguish between insomnia with normal sleep duration, insomnia with short sleep duration, and COMISA. Research has shown that insomnia with short sleep duration are at greater risk of a number of complications, and, as compared to insomnia with normal sleep duration, they may be less likely to respond to cognitive behavioral therapy for insomnia and more likely to require sleep aid medications. For COMISA, a key question is whether one should treat either of the two conditions first or at the same time. There is no one approach that is clearly best. Studies have shown that melatonin and lemborexant can be used with starting CPAP for those patients who are starting treatment of both conditions, as these do not worsen OSA.