Sleep Apnea and Dementia

Insomnia, narcolepsy, sleep apnea- sleep disorders like these are prevalent in Alzheimer’s disease and other forms of dementia. Insomnia, a very common sleep disorder, is typically defined as difficulty falling and staying asleep, leading to sleep that is highly unsatisfactory and leads to fatigue throughout the day (1). While insomnia can be extremely problematic, many treatment modalities exist to lessen the symptoms of insomnia, from lifestyle modifications, foods that enhance sleep, and herbal remedies. On the other hand, sleep apnea (often referred to as Obstructive Sleep Apnea or OSA), can be a challenging condition to treat and can pose serious health risks. OSA is a condition in which the upper airway is obstructed during sleep, which causes interruptions or complete cessation of breathing. This disruption in normal breathing decreases oxygen flow throughout the body, intermittently creating a hypoxic environment in the body by reducing the concentration of oxygen within the blood (2). As with all sleep disorders, OSA can lead to daytime sleepiness. OSA has been linked to increased risk of hypertension, cardiovascular morbidity, and even depression (2,4). Most concerningly, OSA is associated with impaired neurocognitive function and increased risk for Alzheimer’s disease and dementia (3). As noted in the journal Parkinson’s Disease, the most common reported cognitive deficits in people with OSA are reduced executive function and attention capacity deficits such as impaired information processing speed (5). Additionally, OSA is associated with impaired cognition and psychomotor performance.

The likelihood of developing OSA is influenced by a number of factors, including genetics. ApoE4 is the genetic variant most strongly associated with late onset Alzheimer’s disease. However, carriers of this genetic variant also have increased risk for OSA, as research shows that ApoE4 also increases the risk of sleep apnea. Women in particular are more susceptible to OSA if they carry one or two copies of ApoE4 (5). Beyond genetic susceptibility, OSA is largely influenced by modifiable lifestyle factors. OSA is often linked to obesity because those with OSA are likely to have larger tongues and wider pharyngeal wall width (throat width). More weight equals more tissue, and more tissue equals smaller throat space (3). Sleep position can also influence sleep apnea, especially in obese individuals. A clinical study looked at sleep position and dementia in those with sleep apnea. Their results lead to the conclusion that those with dementia are more likely to sleep in the supine position, although the exact mechanism of action is still unknown (7).

Recent studies have shown that approximately 50% of those with Alzheimer’s disease will or have experienced OSA in their lifetime (6). A well studied mechanism of action supporting this connection involves beta amyloid plaques. A buildup of beta amyloid plaques in the brain are characteristic of Alzheimer’s disease. During the preclinical stages of Alzheimer’s disease, soluble beta amyloid becomes insoluble and aggregate into plaques. Hypoxia induces signals in the cell that promote inflammatory pathways. Oxidative stress occurs as a direct result of the decrease of oxygen levels in the blood, which decreases the pH of the blood. Additionally, hypoxia shunts the cell to create energy through anaerobic respiration, which indirectly activates proinflammatory pathways and creates oxidative stress. This increase in inflammation, coupled with the disruption of natural sleep cycles, increases the production of beta amyloid plaque (6). In the presence of genetic predisposition from ApoE4, this plaque production is boosted further. Furthermore, under healthy sleep conditions, beta amyloid plaques are naturally cleared. The lack of healthy sleep results in increased production as just described, as well as decreased clearance (8). In fact, even one night of sleep deprivation was shown to cause an increase in AB production, especially in the areas of the brain that can contribute to negative mood (7).

The great news is, OSA can be treated very effectively. Before 1981, the only cure was a tracheostomy. In 1981, the Continuous Positive Airway Pressure (CPAP) was developed as an alternative cure (4). This treatment involves a pressurized mask worn during sleep (9). Most studies have shown that CPAP slows cognitive decline (6). Unfortunately, some studies have shown inconsistent results and improvements due the placebo effect (4). Alternatively, many individuals find relief when using a HEPA filter, which in brief, purifies the air, thinning it and making it easier to breathe. Additionally, in those suffering from sleep apnea as a result of obesity, weight loss is an effective treatment (that will also help reduce the risk of Alzheimer’s disease). Remember to always practice good sleep hygiene and when in doubt, get a sleep study to assess your need for sleep apnea treatment.

References:

1. Raman, S. and Roy, A. (2009). Insomnia- a general review. Drug Invention Today, 12(1): 123-126.
2. Knoepke, C. and Aloia, M. (2009). Proposed mechanisms of cognitive dysfunction in obstructive sleep apnea. Primary Psychiatry, 16(10): 51-56.
3. Sutherland, K. and Cistulli, P. (2015). Recent advances in obstructive sleep apnea pathophysiology and treatment. Sleep and Biological Rhythms, 13: 26-40.
4. El-Ad, B. and Lavie, P. (2005). Effect of sleep apnea on cognition and mood. International Review of Psychiatry, 17(4): 277-282.
5. Kaminska, M. et al. (2015). The interaction between obstructive sleep apnea and Parkinson’s Disease: possible mechanisms and implications for cognitive function. Parkinson’s Disease, 1-11.
6. Polsek, D. et al. (2018). Obstructive sleep apnoea and Alzheimer’s disease: In search of shared pathomechanisms. Neuroscience and Biobehavioral Reviews, 86: 142-149.
7. Levendowski, D.J. et al. (2019). Head position during sleep: potential implication for patients with neurodegenerative disease. Journal of Alzheimer’s Disease, 67: 631-638.
8. Cedernaes, J., et al. (2017). Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer’s disease. Sleep Medicine Reviews, 31: 102-111.
9. Richards, K.C. et al. CPAP adherence may slow 1-year cognitive decline in older adults with mild cognitive impairment and apnea. The American Geriatrics Society, 00(00): 1-7.
10. Bresden, D.E. (2017). The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline. New York, New York: Penguin Random House.