New Research on Sleep Apnea
Recent studies increase awareness about risks for this widely undiagnosed and undertreated condition.
Obstructive sleep apnea (OSA) is a common disorder that causes people to stop breathing repeatedly through the night. Apnea episodes can last 10 seconds or more and occur hundreds of times each night, resulting in reduced blood oxygen concentration. Warning signs include loud snoring, gasping, or choking during sleep, and it’s common for those with sleep apnea to wake up feeling fatigued or irritable and to experience headaches and mood swings. Left untreated, OSA can lead to serious health problems, including depression and anxiety, high blood pressure, pulmonary diseases, cardiovascular disease, and increased mortality.
Furthermore, sleep disorders such as sleep apnea and insomnia have been found to contribute to incremental increases in health care utilization and expenditures. Recent research also provides insight into apnea’s association with an increased COVID-19 infection risk; its damaging effects on the brain, including a possible link to dementia; opportunities to improve adherence to sleep apnea treatments; benefits and challenges of current treatment options; and the possibility of future oral pharmacological treatment options.
Health Care Utilization and Expenditures
Sleep Apnea Treatment
Despite the proven benefits of CPAP treatment, roughly 50% of people don’t fill their prescriptions or stop using the devices within the first year, primarily due to discomfort. Other treatment options such as oral appliances may be used by those who can’t tolerate PAP therapy; these enlarge the airways by moving the tongue or mandible forward. However, these options take time to get used to and are frequently perceived as intrusive or bulky, resulting in insufficient use. Surgical treatments are available; however, they’re invasive and pose additional concerns for older adults.2
CPAP Therapy for Older Adults
Potential Drug Treatment
Research demonstrates that carbonic anhydrase (CA), an enzyme responsible for conversion between carbonic acid and carbon dioxide in the body, is elevated in people with sleep apnea.4 A new Swedish study indicates that CA inhibitors may have a future role in the treatment of OSA. The researchers conducted a four-week randomized controlled trial, with 59 patients with moderate or severe sleep apnea completing the study. Patients were randomly assigned to two groups receiving either 400 or 200 mg of the CA inhibitor and a third group (the control group) received placebo. Overall, treatment with the CA inhibitor reduced the number of breathing pauses and promoted oxygenation during the night. Among patients receiving the higher dosage, the number of breathing pauses decreased by approximately 20 per hour. For about one-third of patients, breathing pauses decreased by about 50%, and for 1 in 5, the number of pauses fell by at least 60%.5 The study results, together with the drug’s established safety data, provide support for continued research on CA inhibition as a potential new treatment for OSA.
Women at Risk
The study authors noted that there’s a lack of awareness and underreporting of sleep apnea in women, which places them at risk of serious systemic diseases such as hypertension, cardiovascular disease, and stroke. The authors also observed that these women were likely to report fatigue, headaches, masticatory muscle soreness upon awaking, and sleep problems such as insomnia to their doctors.7 It’s important that attending physicians make the connection, ask the right questions, and seek further diagnosis in cases of suspected sleep apnea.
Cognitive Behavior Therapy
A recent Australian study of 145 patients with COMISA found that when comorbid insomnia symptoms are treated with cognitive and behavioral therapy for insomnia (CBTi), there’s increased acceptance and use of CPAP therapy to treat sleep apnea. Providing CBTi to patients decreased rejection of CPAP devices by 87% and increased long-term CPAP use by one hour each night over the first six months. At six months, combined CBTi and CPAP therapy led to significant improvements, including the following9:
• 52% in global insomnia severity, compared with 35% in the control group;
• 48% in nighttime insomnia complaints, compared with 34% in the control group; and
• 30% in dysfunctional sleep-related cognitions, compared with 10% in the control group.
The study suggests that patients should be screened for insomnia symptoms and, if present, be treated with CBTi to improve subsequent acceptance and use of CPAP therapy for those with COMISA.
The research team analyzed data from 137,917 participants enrolled in the Nurses’ Health Study, Nurses’ Health Study II, and the Health Professionals Follow-up Study. People with OSA spending less than four hours per week sitting watching TV were compared with those spending more than 28 hours per week doing so. The researchers found that less active participants had a greater chance of developing OSA. Those with very sedentary jobs were at a 49% higher risk of developing the sleep breathing disorder than were those in active occupations. Study participants who watched more than four hours of TV each day had a 78% higher risk of developing OSA than did the least sedentary among study participants. Higher levels of physical activity and fewer sedentary hours were associated with lower OSA incidence.10 The study’s results suggest that promoting an active lifestyle may help reduce excess weight, cardiovascular disease, and OSA incidence.
Sleep Apnea and the Brain
Physical and Chemical Changes
Link Between Sleep Apnea and Dementia
Another study investigated the extent of Alzheimer’s-like indicators in autopsy tissue from the hippocampi of 34 people and the brainstems of 24 people with OSA.12 The researchers looked for both amyloid plaques and neurofibrillary tangles, another known indicator of Alzheimer’s disease. In the disease, plaques and tangles first appear in the hippocampus and a nearby cortical area—both structures associated with memory—before spreading to the rest of the cortex. While the study found both plaques and tangles in the brains of people with sleep apnea, the plaques were more strongly associated with severe sleep apnea.
— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.
2. Kim J, Tran K, Seal K, et al. Interventions for the treatment of obstructive sleep apnea in adults: a health technology assessment. NCBI Bookshelf website. https://www.ncbi.nlm.nih.gov/books/NBK535532/. Published March 2017.
3. Martinez-Garcia MA, Oscullo G, Ponce S, et al. Effect of continuous positive airway pressure in very elderly with moderate-to-severe obstructive sleep apnea pooled results from two multicenter randomized controlled trials. Sleep Med. 2022;89:71-77.
4. Hoff E, Zou D, Schiza S, et al. Carbonic anhydrase, obstructive sleep apnea and hypertension: effects of intervention. J Sleep Res. 2020;29(2):e12956.
5. Hedner J, Stenlöf K, Zou D, et al. A randomized controlled trial exploring safety and tolerability of sulthiame in sleep apnea [published online February 24, 2022]. Am J Respir Crit Care Med. doi: 10.1164/rccm.202109-2043OC.
6. Hwang D, Chen A, Arguelles J, et al. 680 Impact of obstructive sleep apnea and positive airway pressure therapy on COVID-19 outcomes. Sleep. 2021;44(Suppl 2):A266.
7. Emodi-Perlman A, Soliman J, Frideman-Rubin P, Eli I. Symptoms of nocturnal masticatory muscle activity among women of different age groups and their association to obstructive sleep apnea—a cross sectional study. J Clin Med. 2022;11(5):1199.
8. Zhang Y, Ren R, Lei F, et al. Worldwide and regional prevalence rates of co-occurrence of insomnia and insomnia symptoms with obstructive sleep apnea: a systematic review and meta-analysis. Sleep Med Rev. 2019;45:1-17.
9. Sweetman A, Lack L, Catcheside PG. Cognitive and behavioral therapy for insomnia increases the use of continuous positive airway pressure therapy in obstructive sleep apnea participants with comorbid insomnia: a randomized clinical trial. Sleep. 2019;42(12):zsz178.
10. Liu Y, Yang L, Stampfer MJ, Redline S, Tworoger SS, Huang T. Physical activity, sedentary behaviour and incidence of obstructive sleep apneoa in three prospective US cohorts. Eur Respir J. 2022;59(2):2100606.
11. Li X, Liu Y, Rich SS, Rotter JI, Redline S, Sofer T. 0291 Sleep disordered breathing associated with epigenetic age acceleration: evidence from the multi-ethnic study of atherosclerosis. Sleep. 2019;42(Suppl 1):A118-A119.
12. Owen JE, Benediktsdottir B, Cook E, Olafsson I, Gislason T, Robinson SR. Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep. 2021;44(3):zsaa195.
13. Macey PM, Sarma MK, Nagarajan R, et al. Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex. J Sleep Res. 2016;25(4):390-394.
14. Jackson ML, Cavuoto M, Schembri R, et al. Severe obstructive sleep apnea is associated with higher brain amyloid burden: a preliminary PET imaging study. J Alzheimers Dis. 2020;78(2):611-617.