We have just completed the 29th Advances in Diagnosis and Treatment of Sleep Apnea and Snoring course in San Francisco. It is so enjoyable to be one of the course directors, where we can think about the newest developments in the field and other topics to incorporate as we develop the program. As I do every year, I share what I view as some of the highlights of the presentations on this blog. I do not mean to exclude talks that were fascinating across the board, but I am focusing on topics that I do not typically discuss here.

Aric Prather, PhD from the University of California, San Francisco (UCSF) spoke about insomnia and OSA. He presented data showing that CPAP can improve sleep quality and quantity, highlighted by a discussion of the randomized MATRICS Trial. This study examined those with coexisting (or comorbid) insomnia and obstructive sleep apnea. They examined whether treating insomnia with cognitive behavioral therapy for insomnia (the most effective treatment for insomnia) improved adherence to CPAP, whether before or after starting CPAP or not at all. They showed that CPAP adherence was relatively low in this group (34-42%) and that cognitive behavioral therapy for insomnia improved sleepiness more quickly but did not improve CPAP adherence.

Rochelle Zak, MD from UCSF spoke about menopause and OSA, a hugely important topic. Menopause is associated with substantial increases in the prevalence of OSA, independent of changes in age and body weight that may occur. Dr. Zak presented a thorough assessment of studies regarding hormone replacement therapy, showing that bioidentical hormones may prevent development of OSA. It is important to note that hormone replacement therapy is not advocated primarily for its impact on OSA, given that there are potential risks.

Diana Thiara, MD from UCSF, the medical director of the UCSF Weight Management Clinic, spoke thoughtfully about obesity management. Because everyone asks her which diet is best, she addressed that topic first, indicating that the best diet for weight loss is the one that a patient can follow over the long term. There is no proven benefit of one diet vs. another based on macronutrient diet (like low-carb, Paleo, etc.). There may be other benefits of diets, but for weight loss, the combination of self-monitoring (tracking what they are eating) and calorie reduction (about 500 calories per day) is key. She echoed the words of Michael Pollan: “Eat food. Not too much. Mostly plants.” She then emphasized that weight cycling (losing then regaining weight) is especially bad because it often involves loss of muscle mass.

Dr. Thiara then discussed the wide range of medications that are FDA-approved for weight loss. The glucagon-like peptide-1 (GLP-1) receptor agonists act in the hypothalamus (in the brain) to promote satiety (sense of feeling full), slow emptying of the stomach, and increase insulin secretion and sensitivity. She reviewed a number of studies, including the SELECT Trial that showed that not only did semaglutide (the medication in Wegovy for weight loss or Ozempic for diabetes) achieved weight loss but also reduced cardiovascular events (stroke, heart attack) by 20%. These medications do have important potential side effects, ranging from nausea and vomiting to pancreatitis and other concerns.

Tirzepatide (Zepbound for weight managment, Mounjaro for diabetes) combines a GLP-1 receptor agonist with gastrointestinal inhibitory polypeptide (GIP) increases lipolysis and fatty acid synthesis. The SURMOUNT-1 trial of tirzepatide shows even-greater levels of weight loss (20%), particularly in women under the age of 50. The SURMOUNT-OSA trial is examining tirzepatide for treatment of OSA. Results were anticipated early this year, but it sounds like these may not be available imminently. As one might expect, there are many medications in development and various stages of testing as weight loss medications. One of these, retatrutide, adds glucagon to the two components of tirzepatide. There may be even greater weight loss, but the question will be related to potential side effects.

Jolie Chang, MD from UCSF spoke about the decision making process for patients with OSA who are considering surgery. The UCSF team has examined the potential of patient education videos in improving patient comfort with making treatment decisions. They showed that videos were particularly helpful for those patients with substantial uncertainty about treatment decisions. This is actually the reason why I have developed a set of videos available on my YouTube channel. I hope you enjoy them!

Nalaka Gooneratne, MD from the University of Pennsylvania spoke again about complementary and alternative medicine in sleep disorders. I have adopted his approach of using melatonin mainly in those over the age of 55 with higher doses (10 mg) for a couple of weeks 1-2 hours before bedtime to see if it provides benefit, as peak levels in the body are 1 hour after taking it by mouth. If it does not, it is less likely that melatonin will be helpful. If it is helpful, melatonin dose can be adjusted downwards, monitoring the continued effect. The reason for use primarily in older adults is that the body’s own production of melatonin naturally declines over time, making melatonin taken by mouth more likely to provide something that the body may not be making sufficiently when we get older. While cognitive hehavioral therapy is still the most-beneficial treatment for insomnia, melatonin and other mind-body interventions (yoga, tai chi, meditation) and other treatments (acupuncture/acupressure) appear to have some benefits.

Liza Ashbrook, MD from UCSF spoke about glymph and a process in the brain for clearance of metabolic byproducts produced during the day that has some similarities to the lymphatic system in the rest of the body. There is intriguing evidence that the clearance of beta amyloid, tau, and alpha-synuclein proteins (all implicated in neurodegenerative diseases like dementia) is slowed by sleep deprivation, especially with disruption of slow wave sleep. The challenge may be that, as we age, we have less slow wave sleep, without specific treatments that can increase this type of sleep.

Allan Pack, MBChB from the University of Pennsylvania spoke eloquently about the fact that proteins like amyloid beta and tau start accumulating in the brain many years before the appearance of dementia and cognitive impairment. The deposition of these proteins may decrease the quality of sleep, resulting in a cycle of worsening the same deposition of these proteins. There is the possibility of whether OSA can be a cause of dementia, including Alzheimer’s Disease, or whether the opposite is true. Numerous large studies have shown that untreated moderate to severe OSA can be associated with the development of dementia (with the OSA starting before diagnosis of dementia). The potential would be for intervention to reduce or eliminate progression of disease. There is some evidence that treatment of OSA with CPAP improves cognitive function or slows progression of cognitive impairment, but the evidence comes from small, non-randomized studies. Perhaps the most exciting recent finding is the identification of p-Tau217 as blood biomarker for predicting development of Alzheimer’s Disease, a step that will make research much easier.

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