- Obstructive sleep apnea, the most common type of sleep breathing disorder, is a risk factor for cerebrovascular disease, conditions that affect blood vessels in the brain.
- Obstructive sleep apnea is also linked to mild cognitive impairment and Alzheimer’s disease, but the mechanisms underlying this association are not well understood.
- Dementia is also associated with abnormalities in the brain’s white matter that are hallmarks or markers of cerebrovascular diseases.
- A recent observational study shows that severe obstructive sleep apnea and reduced deep sleep were independently associated with white matter abnormalities related to cerebrovascular diseases in cognitively unimpaired older adults.
- These findings show that severe obstructive sleep apnea and poor sleep quality can lead to an increase in the biomarkers of cerebrovascular disease, potentially increasing the risk of cognitive decline and stroke.
Obstructive sleep apnea is the most common type of sleep-breathing disorder that affects nearly a billion individuals across the globe.
A recent study published in Neurology suggests that obstructive sleep apnea and a reduction in deep sleep, also known as slow-wave sleep, were independently associated with an increase in white matter abnormalities in the brain.
The white matter abnormalities assessed in the study are known markers of cerebrovascular disease and are also observed in mild cognitive impairment and Alzheimer’s disease.
The findings from this observational study thus suggest that obstructive sleep apnea and poor sleep quality could potentially lead to increased white matter abnormalities, subsequently increasing the risk of dementia and stroke.
The study’s author Dr. Diego Carvalho, a neurologist at the Mayo Clinic in Rochester, MN, told Medical News Today:
“White matter abnormalities increase with aging and may contribute to cognitive decline, dementia, and stroke. Since there is no treatment to reverse or slow them down other than risk factor prevention, it is important to understand what may contribute to their development.”
“In our study, we found that severe sleep apnea and decreased deep sleep were associated with more white matter abnormalities. Although we cannot infer a direct causal relationship with a cross-sectional study design, the findings raise the possibility that sleep interventions may prevent the progression of white matter disease. Although there is already compelling evidence that sleep apnea is involved in white matter abnormalities, the potential role of slow-wave sleep (or deep sleep) in white matter health is much less understood,” added Dr. Carvalho.
Sleep quality and dementia
Obstructive sleep apnea is a sleep-breathing disorder characterized by episodes of interruption of breathing due to partial or complete blockage of the upper airway. The episodes of reduced breathing are known as hypopnea, whereas apnea refers to events involving a complete blockage of the upper airway.
The apnea-hypopnea index (AHI) describes the number of apnea and hypopnea events per hour. Specifically, obstructive sleep apnea involves at least five such episodes of apnea or hypopnea per hour.
The interruption of breathing triggers a compensatory response that leads to arousal from sleep. Thus, obstructive sleep apnea leads to sleep disturbances and an experience of feeling unrefreshed after sleep.
Several studies have shown that poor sleep quality is associated with an increased risk of cognitive decline and dementia.
The accumulation of misfolded deposits of the amyloid-beta and tau proteins is a hallmark of Alzheimer’s disease. A previous study showed a higher accumulation of the amyloid-beta protein in the brains of individuals experiencing excessive daytime sleepiness.
In contrast, a brain imaging study showed that cognitively unimpaired individuals with higher tau levels in their brains were at an increased risk of obstructive sleep apnea.
These studies suggest a bidirectional relationship between sleep quality and pathological changes associated with Alzheimer’s disease.
Why white matter changes have an impact
In addition to the accumulation of misfolded proteins, individuals with dementia also show damage to neurons.
The brain tissue can be categorized into white matter and gray matter. The gray matter consists of the cell bodies of neurons, whereas the white matter consists of axons that transmit information.
Several of the axonal processes in the white matter are encased in an insulating layer called the myelin sheath. The myelin sheath gives white matter its color and allows the axons to conduct electrical impulses more rapidly and efficiently.
Individuals with dementia and mild cognitive impairment show abnormalities in the white matter. Some of these white matter abnormalities, such as white matter hyperintensities and a decline in the integrity of the white matter tract, are also markers for cerebrovascular diseases, which are diseases of the blood vessels in the brain.
White matter hyperintensities are hyperintense regions identified using MRI that represent lesions of white matter generally caused by cerebral small vessel disease.
The integrity of the white matter tract is measured in terms of fractional anisotropy using a technique called diffusion tensor imaging. These white matter abnormalities due to damage to blood vessels may contribute to cognitive decline.
Sleep and cerebrovascular health
Sleep disorders such as obstructive sleep apnea are also associated with increased risk of cerebrovascular diseases. Thus, sleep disorders could potentially lead to cerebrovascular disease-related white matter abnormalities and increase the risk of dementia.
For instance, there is evidence from the authors’ own work showing that individuals with daytime sleepiness have elevated levels of the neurofilament light chain protein in their blood, though research evidence is contradictory.
The neurofilament light chain protein is a protein associated with the myelin sheath covering the axons of neurons. Thus, elevated neurofilament light chain protein levels suggest damage to myelinated axons and, thus, white matter damage.
In the present study, the researchers examined the association between sleep quality, including the presence of obstructive sleep apnea, with white matter abnormalities in the brain of cognitively unimpaired individuals.
A study on sleep and cognitive impairment
The new study consisted of 140 individuals participating in the Mayo Clinic Study of Aging (MCSA), a population-based cohort study that aims to characterize the prevalence and risk factors associated with mild cognitive impairment and dementia.
The study included individuals who had previously undergone a brain MRI scan and at least one polysomnography test as a part of the MCSA study.
A polysomnographic study is a sleep study that assesses multiple parameters associated with sleep, including brain waves, breathing and heart rate, and blood oxygen levels. The average duration between the brain MRI scan and the polysomnography test was 1.74 years.
The researchers aimed to only include participants who were cognitively unimpaired at the time of both the MRI and the polysomnography test. The study consisted of 90.7% of the participants who were cognitively unimpaired at the time of both assessments.
Only participants with obstructive sleep apnea were included in the study. These participants were categorized as having either mild, moderate, or severe obstructive sleep apnea on the basis of the number of episodes of apnea and hypopnea per hour.
Sleep quality and cerebrovascular biomarkers
The researchers first examined the association between sleep patterns and white matter abnormalities. Sleep can be divided into the non-rapid eye movement (NREM) and rapid eye movement (REM) phases.
Furthermore, the NREM phase can be further subdivided into N1-N3 phases, with the N1 being the lightest sleep phase and N3 involving deep sleep. These phases show differences in their patterns of brain waves, eye movements, and muscle tone.
Using brain waves collected during polysomnography, the researchers found that a lower fraction of time spent in the N3 phase or slow wave sleep was associated with elevated levels of white matter damage.
This association was present after accounting for variables such as age, sex, genetic risk of Alzheimer’s disease, and cardiovascular risk factors.
In a separate analysis, the researchers looked at the association between obstructive sleep apnea severity and markers of white matter damage. They categorized patients as either having severe or mild-to-moderate obstructive sleep apnea and matched individuals from the two groups for age, sex, and N3 sleep levels for this analysis.
Individuals with severe obstructive sleep apnea showed higher white matter abnormalities than those with mild-to-moderate.
Individuals in the two groups did not show differences in cardiometabolic risk factors, but the individuals with severe obstructive sleep apnea showed higher arousal levels. This indicates the fragmentation of sleep in individuals with severe obstructive sleep apnea.
Dr. Sandra Narayanan, a board-certified vascular neurologist and neuro-interventional surgeon at Pacific Stroke & Neurovascular Center at Pacific Neuroscience Institute in Santa Monica, CA, not involved in the research told us that these findings show that, while obstructive sleep apnea is associated with cardiovascular disease, it could independently increase the risk of cerebrovascular diseases.
Dr. Narayanan said: “[Obstructive sleep apnea] is an important vascular comorbidity, as it is significantly associated with an increased risk of hypertension, cardiovascular disease, and stroke. This study demonstrates a separate association of OSA with imaging biomarkers of cerebrovascular disease.”
Strengths and limitations
Some of the previous studies showing a link between sleep quality and white matter abnormalities have not controlled for cardiometabolic risk factors. These cardiometabolic factors can increase the risk of cerebrovascular conditions, such as stroke, thus potentially biasing the results.
One of the strengths of the present study was that the researchers controlled for cardiometabolic risk factors.
The authors acknowledged that their study had a few limitations. They noted that they only collected sleep data during the initial few hours of sleep.
This could have biased the data on sleep patterns. For instance, the period of REM sleep tends to increase during the night, whereas the duration of deep sleep tends to decline.
Dr. Narayanan noted: “While the imaging biomarkers of CVD noted in this study were not independently linked during the course of this study to the development of incident stroke, the presence of white matter hyperintensities is strongly associated with cognitive impairment, stroke, and death in numerous other studies.”
“Fractional anisotropy (FA) is a marker of white matter integrity, as noted in diffusion tensor imaging (DTI),“ she explained. “Decreased FA is associated with other neurodegenerative disorders such as Alzheimer’s dementia and Parkinson’s disease, but has a poor prognostic value for motor recovery following stroke.”
The authors also noted that the study had an observational design, and further studies are needed to show that obstructive sleep apnea and reduced slow-wave sleep can cause an increase in the biomarker of cerebrovascular disease.
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