Obstructive sleep apnea and cognitive dysfunction

Obstructive sleep apnea (OSA) affects up to 5% of the population in Western countries, but as many as 80% of cases remain undiagnosed.^1,2 Prevalence increases with age, peaking at approximately 60 years.1,3 Although 1 in 5 adults has mild OSA, only 1 in 15 has a moderate to severe case.¹

Obesity is a significant risk factor, partly because layers of fat adjacent to the pharynx narrow its lumen. A 10% increase in weight leads to a six-fold risk of developing OSA.¹ Thus, the incidence of OSA is expected to rise as the rate of obesity increases in the United States. Other risk factors for OSA include male sex and abnormalities of craniofacial morphology. Frequent alcohol use has also been considered a risk factor since it depresses the central respiratory drive and enhances muscle relaxation.^3,4

Patients with untreated OSA may present with conditions such as hypertension, coronary artery disease (including MI), diabetes, heart failure, stroke, and cognitive dysfunction. Although these conditions are commonly treated without a search for underlying pathology, OSA can be a major contributor. Previous research has focused on the cardiac effects of untreated OSA, such as hypertension, stroke, and arrhythmias. ^5,6 However, a mechanism that causes cardiac dysfunction may also cause cognitive dysfunction resembling dementia. Failure to diagnose and treat OSA effectively may result in improper management of this dementia. With proper treatment, its progression may be halted—although the condition may not be completely reversed.

At present, no optimal treatment options are availablefor OSA. Continuous positive airway pressure (CPAP) therapy is the first-line treatment, but patient adherence is only 46% to 70% because of discomfort caused by the mask.^3,7

Physiology

OSA is defined as periods of apnea (cessation of breathing for longer than 10 seconds) or hypopnea (reduction but not complete cessation of airflow to less than 50% of normal) that occur throughout sleep. These are caused by partial or complete obstruction of the upper airway, usually the oropharynx, which inhibits inspiratory airflow⁸ (see Figure 1).

Airway closure results from the relaxation during sleep of skeletal muscles—specifically, the pharyngeal dilator muscles and the genioglossus, which maintain the tongue in the anterior position when the person is supine. Too much muscle relaxation allows the tongue to slide posteriorly, partially or completely occluding the airway and causing the typical loud snoring and sudden choking and gasping for air. Other contributing anatomic anomalies include excessive soft palate tissue and enlarged tonsils, tongue base, or uvula.

Mechanism of action Cyclical oxygen desaturation occurs with each pause in breathing that stimulates arousal from sleep. In rapid eye movement (REM) sleep, muscle tone is most relaxed and apnea episodes are prolonged, with severe desaturations, often 60% to 70% lower than normal.⁹ Following each apneic or hypopneic event, a surge of sympathetic activity occurs, stimulating transient tachycardia and increasing BP.³ Over time, cardiac hypertrophy, arrhythmias, and cor pulmonale can result.¹⁰ Each interruption of their sleep pattern prevents patients from reaching the deep sleep stage. They wake feeling unrested and experience daytime somnolence.

OSA and motor vehicle accidents Patients with OSA perform poorly on driving-simulator tests ^2,3,11,12
and have a 2% to 7% greater risk of a motor vehicle accident (MVA) caused by driver sleepiness, fatigue, and inattentiveness.² Up to 21% of patients who present to the emergency department (ED) following an MVA have undiagnosed OSA.² The true number may be even higher than reported, given that a significant number of crashes are attributed to comorbid conditions such as stroke and MI when OSA may have been a contributing cause. ED staff should be aware of the seriousness of OSA and screen MVA patients for this condition.

Cognitive impairment

Untreated OSA has been strongly implicated in contributing to cardiovascular morbidity by increasing the
risk of atherosclerosis, ischemia, and stroke⁵ (see Table 1). The proposed mechanism is increased levels of oxidative stress that contribute to excess free radical production,¹³ soluble adhesion molecules,^14,15 and decreased levels of nitric oxide (NO), a potent vasodilator. 16 Repeated transient hypopnea/apnea and reoxygenation events resulting from untreated OSA also affect cerebral oxygenation and blood flow velocity.¹⁷This produces a condition similar to myocardial hypoxia, resulting in increased production of free radicals and adhesion molecules and decreased levels of NO.¹⁸

Free radicals are highly reactive substances capable of doing extensive damage to healthy tissue if not properly contained within the mitochondria.¹⁸ NO suppression triggers vasoconstriction, elevated BP, and decreased oxygen supply to local brain tissue.¹⁶ It has been hypothesized that severe oxygen desaturation and decreased blood flow velocity to brain tissue may cause an infarct, similar to a cardiac infarct, resulting in death of brain tissue with permanent neuropsychological dysfunction.¹⁷ After several years of untreated OSA, the impact may become clinically evident as dementia. This destructive process is thought to represent vascular dementia rather than the degenerative dementia commonly seen in Alzheimer's disease and Parkinson's disease.^19,20 Patients currently classified as having dementia may not be treated properly if underlying OSA is not considered or treated. Effective CPAP therapy in patients with OSA can increase the NO concentration and rapidly decrease free radical and adhesion molecule release.^13,15 Thus, further cognitive damage may be prevented with adequate treatment.