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Evidence documents that Obstructive Sleep Apnea (OSA) is closely associated with cognitive decline (Kanbay et al. 2017). OSA is believed to cause brain injury in multiple ways. First, OSA causes oxygen desaturation, leading to blood oxygen levels falling below 90%. Sometimes blood oxygen levels drop below 90% multiple times an hour (Dodig et al. 2018). This causes cellular damage to the brain. Cellular damage to brain cells exacerbates cognitive decline and worsens outcomes for patients diagnosed with dementia (Cooke et al. 2009). Additionally, OSA increases the prevalence of biomarkers, like C-reactive protein, which predicts cognitive decline (Wu et al. 2016). Sánchez et al. found that cognitive deficits in attention, vigilance, short-term recall, perception, learning abilities, constructional abilities and executive functions are most commonly observed in patients with OSA (2009). Based on a meta-analysis of available data, these researchers found that CPAP therapy can reverse some of these aforementioned deficits (Sánchez et al. 2009). While not capable of completely reversing all kinds of cognitive deficits caused by OSA, CPAP therapy can maintain cognitive function and slow decline in patients diagnosed with dementia (Cooke et al. 2009). Due to the lack of medical awareness regarding the link between OSA and cognitive decline, there has been limited screening of vulnerable populations (Crawford-Achour et al. 2015).
Anatomical Changes in the Brain Associated with OSA
Two peer-reviewed articles explore anatomical changes that occur in the brain in association with Obstuctive Sleep Apnea (OSA). Rosenzweig et al. found that, in comparison to healthy individuals, patients diagnosed with OSA experienced hypotrophy (loss of cells) in the left hippocampus, the bilateral pallidus and the mid-posterior section of the corpus callosum (2016). After just one month of CPAP therapy, the patients no longer showed significant hypotrophy when compared to healthy individuals (Rosenzweig et al. 2016). Indeed, OSA patients undergoing CPAP therapy exhibited significant hypertrophy in the thalamus, thus regaining lost brain matter caused by obstructive sleep apnea. Compared to OSA patients only undergoing lifestyle therapy, patients treated with CPAP therapy had statistically significant improvements in verbal episodic memory and daytime solomnence (Rosenzweig et al. 2016). Rosenzweig et al. postulate that their study indicates that the thalamus is physically vulnerable to disruption of sleep-wake cycles and to oxygen desaturation (2016). In a large population-based study by Zuurbier et al. the magnitude of oxygen desaturation caused by OSA was statistically significant in predicting white matter atrophy (2016). Additionally, Zuurbier et al. found that increased oxygen desaturation led to a smaller hippocampus and a smaller white matter parietal volume (2016). The researchers' statistical model showed that oxygen desaturation alone, not AHI or nighttime arousals, was the primary cause of brain damage (Zuurbier et al. 2016).
Improvements in Cognitive Performance of OSA Patients (all ages) Undergoing CPAP Therapy
Peer-reviewed articles reveal that, in the general population, patients diagnosed with OSA can reverse or partially reverse cognitive impairments associated with an OSA diagnosis (Aloia et al. 2006). Aloia et al. state that, "Patients who used CPAP for at least 6 hours a night were nearly eight times as likely to demonstrate normal memory abilities compared with patients who used CPAP for 2 or fewer hours a night," (2006). After three months of CPAP therapy, 68 percent of patients who used their machines more than 6 hours a night exhibited normal memory ability. Contrastingly, only 21 percent and 44 percent of "poor" and "moderate" CPAP users, respectively, exhibited normal memory after three months (Aloia et al. 2006). Sánchez et al. performed a 2009 meta-analysis of all available data at the time and found that CPAP therapy improves some areas of cognitive function for patients diagnosed with OSA. Barnes et al. found that patients with OSA saw statistically significant improvements in verbal fluency and vigilance after CPAP therapy (2002). More recently, Pecotic et al. conducted research on 40 patients diagnosed with OSA (mean age 58.39) and found that all 23 patients diagnosed with "severe" OSA experienced gains in psychomotor and cognitive performance after 6 months of therapy (2018). The greatest gains in therapy were seen in self-reported daytime sleepiness and reaction times to complex psychomotor limb coordination tests (Pecotic et al. 2018). This study ensured its patients were compliant with their machines, so as to ensure consistent research results.
Improvements in Cognitive Performance of Elderly OSA Patients Undergoing CPAP Therapy
Researchers have shown that OSA exacerbates age-related cognitive decline (Crawford-Achour et al. 2015). Additionally, researchers have pointed out that there is a high prevalence of OSA in elderly populations (Crawford-Achour et al. 2015). McMillan et al. conducted research on 34 patients above the age of 64 who were diagnosed with sleep-disordered breathing (2013). They randomly assigned half the patients to best supportive care (BSC) and the other half to CPAP therapy. After 6 months, patients assigned to the CPAP group experienced greater gains in the cognitive domains of attention and executive function compared to the BSC group (McMillan et al. 2013). Additionally, patients in the CPAP group saw a greater reduction in oxygen desaturation events. However, between these two groups, there was not a statistically significant difference in reported daytime sleepiness or in memory. Thus, McMillan et al. concluded that a reduction in OSA-related hypoxia was the reason for observed cognitive improvements (2013). Crawford-Achour et al. performed research on a large cohort of adults above 64 years of age. None of the patients were diagnosed with OSA (2015). The researchers screened 508 participants for OSA. At the end of the screening process, the researchers had identified 126 participants with undiagnosed severe OSA. Those diagnosed with severe OSA were followed up 10 years later to determine if they had received CPAP treatment. Only 26% of the patients in the follow-up group had received CPAP therapy. Those who had received CPAP therapy experienced maintenance of delayed free recall, attention, and executive functioning, compared to the group which did not receive therapy. Patients with OSA who did not receive treatment saw further declines in these areas (Crawford-Achour et al. 2015). Thus, CPAP therapy is important for preserving cognitive performance in older adults.
Effect of CPAP Therapy on Biomarkers Associated with Cognitive Function
Obstructive Sleep Apnea plays a role in modulating biomarkers associated cognitive function. Kanbay et al. explain that insulin-like growth factor-1 (IGF-1) has neuroprotective effects (2015). These researchers found that patients with OSA had reduced blood serum levels of IGF-1 present. After only three months of CPAP therapy, patients diagnosed with OSA saw significant increases in blood serum levels of IGF-1. Correspondingly, these patients then began to score better on the Min-Mental State Exam (MMSE) The Mini-Mental State Exam is a tool many healthcare providers use to measure cognitive performance (Kanbay et al. 2015). Wu et al. discuss C-reactive protein (CRP) as an inflammatory marker that promotes coronary artery disease and is associated with cognitive deficits (Wu et al. 2016). These researchers found that patients diagnosed with severe OSA had higher blood serum concentrations of CRP. The researchers used the Montreal Cognitive Assessment tool (MoCA) to evaluate cognitive function. Patients with an elevated CRP scored significantly lower on the MoCA. Compared to patients who did not receive CPAP therapy, patients treated with CPAP therapy had reductions in CRP and improvements on the MoCA (Wu et al. 2016). Patients diagnosed with severe OSA,who did not receive therapy, experienced a significant deterioration of memory and had worse cognitive function (Wu et al. 2016).
Effect of CPAP Therapy on Alzheimer's Type Dementia
Researchers established that OSA exacerbates cognitive decline experienced by patients diagnosed with Alzheimer's type dementia (AD) (Cooke et al. 2009). Cooke et al. state that the prevalence of OSA in institutionalized AD patients is over 40% (2009). Cooke et al. performed a study on 5 patients with AD treated with CPAP therapy and 5 patients who discontinued CPAP therapy (2009). The researchers found that the patients who continued CPAP therapy group, "...showed 1.) less cognitive decline with sustained CPAP use, 2.) stabilization of depressive symptoms 3.) stabilization of daytime somnolence, and 4.) significant improvement in subjective sleep quality," (Cooke et al. 2009). Caregivers of these patients also reported better sleep (Cooke et al. 2009). Ancoli‐Israel et al. performed a randomized controlled study on 52 men and women who were diagnosed with moderate AD and OSA (2008). They administered a set of neuropsychological exams at 3 and 6 weeks of CPAP therapy, respectively. (can you find the type of neuropsychological exam the researchers used?) After 3 weeks, the researchers found statistically significant improvements in cognition of patients undergoing therapeutic CPAP therapy (Ancoli‐Israel et al. 2008).
A lack of awareness of how OSA affects older patients leads to underdiagnoses of the disease in this population (Crawford-Achour et al. 2015). Untreated OSA can lead to exacerbated age-related mental decline. Since OSA is highly prevalent in older populations. Screening for OSAS should be part of the annual wellness examination for anyone 65 years of age and older. Physicians and the general population should be educated on the severe implications of untreated OSA. More research needs to be conducted on the associations between OSA and cognitive function to determine the exact mechanisms by which OSA exacerbates cognitive decline.
Many people with obstructive sleep apnea are undiagnosed. Some are diagnosed but do not use their CPAP machines. Mr. Singer’s research provides objective data and information physicians and nurse practitioners may find useful when educating patients about the importance of being compliant to PAP therapy.
If you have a CPAP machine or another type of PAP machine are you are no longer using your machine, you might benefit from reading “How to Love Your CPAP Machine: Secrets from a sleep specialist”.
If you have obstructive sleep apnea syndrome and you do not have insurance to cover the cost of buying a machine, you might find an affordable CPAP machine online. If you need assistance with using your machine, you may need to make an appointment with a sleep specialist.
Accpchest. (2006, December 11). Memory improves after sleep apnea therapy. Retrieved from https://www.eurekalert.org/pub_releases/2006-12/acoc-mia120606.php
Crawford-Achour, E., Dauphinot, V., Martin, M. S., Tardy, M., Gonthier, R., Barthelemy, J. C., & Roche, F. (2015). Protective Effect of Long-Term CPAP Therapy on Cognitive Performance in Elderly Patients with Severe OSA: The PROOF Study. Journal of Clinical Sleep Medicine. doi:10.5664/jcsm.4694
Jones, S. (2010). Cognitive Effects of Treating Obstructive Sleep Apnea in Alzheimers Disease: A Randomized Controlled Study. Yearbook of Pulmonary Disease,2010, 241-242. doi:10.1016/s8756-3452(09)79275-8
Mcmillan, A., Paniccia, L., Glasser, M., Edison, P., Simonds, A., & Morrell, M. (2013). S2 The impact of continuous positive airway pressure (CPAP) therapy on cognitive function in older people with sleep disordered breathing (SDB) and co morbidity. Thorax,68(Suppl 3). doi:10.1136/thoraxjnl-2013-204457.8
Pecotic, R., Dodig, I. P., Valic, M., Galic, T., Kalcina, L. L., Ivkovic, N., & Dogas, Z. (2018). Effects of CPAP therapy on cognitive and psychomotor performances in patients with severe obstructive sleep apnea: A prospective 1-year study. Sleep and Breathing. doi:10.1007/s11325-018-1642-6
Suri, T., Sharma, S., Kumaran, S., Nehra, A., Nischal, N., & Kalaivani, M. (2017). Neurocognitive impairment in patients with obstructive sleep apnea before and after therapy with continuous positive airway pressure. Sleep Medicine,40. doi:10.1016/j.sleep.2017.11.939
Sustained Use of CPAP Slows Deterioration of Cognition ... (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725246/
Sánchez, A. I., Martínez, P., Miró, E., Bardwell, W. A., & Buela-Casal, G. (2009). CPAP and behavioral therapies in patients with obstructive sleep apnea: Effects on daytime sleepiness, mood, and cognitive function. Sleep Medicine Reviews,13(3), 223-233. doi:10.1016/j.smrv.2008.07.002
Wu, S. Q., Liao, Q. C., Xu, X. X., Sun, L., Wang, J., & Chen, R. (2016). Effect of CPAP therapy on C-reactive protein and cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome. Sleep and Breathing,20(4), 1185-1192. doi:10.1007/s11325-016-1331-2
Zuurbier, L. A., Vernooij, M. W., Luik, A. I., Kocevska, D., Hofman, A., Whitmore, H., . . . Tiemeier, H. (2016). Apnea-hypopnea index, nocturnal arousals, oxygen desaturation and structural brain changes: A population-based study. Neurobiology of Sleep and Circadian Rhythms,1(1), 1-7. doi:10.1016/j.nbscr.2016.04.001
This post is based on the research of Devin Singer. Mr. Singer is a student in the department of Kinesiology and Health Sciences at Virginia Commonwealth University (VCU) Richmond VA @RVA