Sleep Disorder May Cause Brain Inflammation in Parkinson’s Patients

Researchers have long proposed that a sleep disorder may increase inflammatory responses, and may increase the risk of developing various neurodegenerative diseases, including Parkinson’s disease.  A recent study called “Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behavior disorder: a case-control study” published in the journal The Lancet seems to support this claim.

Sleep disorders are quite common and may affect up to one-fourth of adults or even more at any given time. It has been proven beyond doubt that sleep disorders increase the risk of metabolic disorders and cardiovascular diseases.

Multiple studies have also demonstrated that those who suffer from sleep apnea are at a higher risk of developing depression, anxiety and dementia, though the relationship between sleep disturbances and Parkinson’s disease remains poorly understood.

Among the various theories that have been proposed to explain the link between sleep disorders and neurodegeneration is regarding the chronic inflammation processes. Studies have demonstrated that multiple inflammatory markers are elevated in the periphery in those suffering from sleep disturbances.

It is well known that sleep deprivation has grave consequences for mental health, cognition, and may even lead to a disruption of the blood-brain barrier. Sleep loss may also alter the immune responses. However, little is known about the mechanism through which sleep deprivation leads to low-grade inflammation.

Although, it remains unclear that what causes the chronic inflammation in sleep deprivation, and what are the sources of various inflammatory mediators in such condition. However, both animal and human studies have demonstrated the presence of chronic inflammation. It has been shown that these inflammatory mediators further disrupt the so-called blood-brain barrier, and thus leading to low scale chronic inflammation of the brain. It is entirely possible that this very low scale inflammation may trigger neurodegeneration if it persists over an extended period.

Apart from causing low-grade brain inflammation due to chronic sleep issues, research has shown that even short-term deprivation of sleep may have an adverse effect on physical movements, leading to low-frequency tremors.

In one of the studies, Tomczak and colleagues studied the effect of sleep deprivation on trainees of Polish Air Force Academy. These were the subjects who were deprived of sleep for 36 hours during intensive military training. Researchers measured the level of tremor before, during and after completion of 36 hours training, and they found that muscular tremor was increased on sleep deprivation.

Although the underlying mechanism of a tremor caused by acute sleep deprivation and chronic sleep disorder may differ, but what research does indicate that any kind of sleep deprivation would cause worsening of physical movements.

Coming back to the subject, in one of the first studies of its kind Stokholm et al. focused their research efforts on the changes in the brain caused due to a chronic sleep disorder.

For their research, they studied the subjects known to be suffering from rapid eye movement behavior disorder or RBD. RBD is more frequently found in men in comparison to women and is most commonly diagnosed between the age of 50-70. In contrast to an obstructive sleep disorder like sleep apnea, RBD is of central origin, which is caused due to changes in the brain. It is a disease in which a person may display abnormal movements in sleep, especially during rapid eye movement (REM) stage, which is when a person is dreaming. 

Healthy subjects remain relaxed during sleep and rarely display movements or make any sounds while sleeping. However, those suffering from RBD may kick, shout or even scream in dreams. Something that alters their sleep quality, and of those around.

There have been studies earlier that demonstrated the link between RBD, Parkinson’s disease and dementia. However, these studies did not try to study the underlying mechanism. So, to solve this mystery, Stokholm et al. analyzed the brains of 20 individuals diagnosed with RBD, comparing their brain scans with 19 healthy subjects in sleep centers in Barcelona, Spain.

Their research found a higher level of activity of immune cells in the brain, which is the higher activity of microglial cells. They also found the reduced activity in substantia nigra with lower levels of dopamine, when compared to healthy subjects. The low level of dopamine in substantia nigra is characteristic of Parkinson’s. So, for the first time, it was demonstrated that sleep disturbance might be directly responsible for the prevalence of Parkinson’s.

Researchers also demonstrated the higher level of inflammatory changes in the dopamine-producing areas of the brain. Thus, researchers concluded that RBD caused the changes in the brain that were quite similar to the early stages of diseases like dementia and Parkinson’s.

Although many researchers have hypothesized that brain inflammation in sleep disorders may be responsible for neurodegeneration, however, it was the first study to demonstrate the validity of such theories.

Finally, researchers want to develop a better understanding about the early changes in the brain caused due to RBD or other sleep disorders, so that they could understand who is at higher risk of developing dementia or Parkinson’s disease later in life. 

References

1. Stokholm MG, Iranzo A, Østergaard K, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behavior disorder: a case-control study. The Lancet Neurology. 2017;16(10):789-796. doi:10.1016/S1474-4422(17)30173-4
2. Hurtado-Alvarado G, Domínguez-Salazar E, Pavon L, Velázquez-Moctezuma J, Gómez-González B. Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link. J Immunol Res. 2016;2016. doi:10.1155/2016/4576012
3. Tomczak A, Gajewski J, Mazur–Różycka J. Changes in physiological tremor resulting from sleep deprivation under conditions of increasing fatigue during prolonged military training. Biology of Sport. 2014;31(4):303. doi:10.5604/20831862.1127343
4. Unnikrishnan D, Jun J, Polotsky V. Inflammation in Sleep Apnea: An Update. Rev Endocr Metab Disord. 2015;16(1):25-34. doi:10.1007/s11154-014-9304-x