Sleep apnea may raise microbleed risk in brain, lead to dementia or stroke

• Obstructive sleep apnea is associated with upper airway collapse that occurs during sleep. 

• One study found that having moderate to severe obstructive sleep apnea may increase the risk for cerebral microbleeds. 

• The data highlights how obstructive sleep apnea affects brain health and implies that it may increase the risk for greater problems like dementia and stroke.

Obstructive sleep apnea (OSA) is a common problem, affecting over 935 million adults all over the world. The condition involves upper airway collapse that then leads to someone waking up or experiencing drops in oxygen levels. But the possible effects of the condition may extend far beyond interruption of a good night’s sleep.

A recent study published in JAMA Network Open that involved an eight-year follow-up with over 1,400 participants found that there is an increased risk for cerebral microbleeds among adults who have moderate to severe OSA.

Cerebral microbleeds may increase the chances of experiencing symptomatic strokes and dementia. The authors suggest that addressing OSA may be a way to help with stroke and dementia prevention among older individuals.  

Another potential risk posed by obstructive sleep apnea

For this study, researchers examined the relationship between OSA and cerebral microbleeds in older and middle-aged adults. Cerebral microbleeds involve a chronic buildup of certain blood products in the brain. As noted in the study, cerebral microbleeds are linked to a higher risk for symptomatic stroke and dementia and are more common in older adults.

Researchers selected study participants from a subcohort of the Korean Genome and Epidemiology Study. These individuals had undergone polysomnography, which helps to diagnose sleep disorders, as well as MRI exams.

Researchers selected participants who had undergone polysomnography and MRIs at three separate time points. They excluded individuals with a history of cerebrovascular disease or cardiovascular disease, missing covariates, or baseline microbleeds. The final analysis included 1,441 Korean adult participants.

Researchers were able to look at baseline brain data as well as brain data at the four and eight-year follow-ups.

Researchers took into consideration multiple covariates, including regular exercise, smoking status, blood pressure, and body mass index. Researchers did sensitivity analyses excluding participants who used CPAP therapy throughout the follow-up time frame, including a sensitivity analysis to account for the APOE-ε4 gene, which is a genetic variant that increases risk for Alzheimer’s disease.

Researchers divided participants into three categories of OSA: none, mild, and moderate to severe. The average age of participants at baseline was just under fifty-eight years old. At baseline, 436 participants had mild OSA, and 193 had moderate to severe OSA. There was a higher proportion of men, current drinkers, and current smokers in the moderate to severe group, and body mass index was highest in this group as well.

The incidence of cerebral microbleeds was highest in the moderate to severe OSA group. For example, at the eight-year mark, 7.25% of participants in this group had cerebral microbleeds, while only 3.33% of participants in the group without OSA had cerebral microbleeds.

In the first few models, moderate to severe OSA was associated with an increased risk for cerebral microbleeds at the four and eight-year follow-up marks. However, in the final model, which adjusted for the most factors, the risk for cerebral microbleeds was only increased at the eight-year mark. For this, the risk was about double that of the group that did not have OSA.

Mild OSA was not associated with an increased risk for cerebral microbleeds.

2 times increased microbleed risk

In the sensitivity analyses, researchers found similar results. When considering the APOE-ε4 genotype, they used a subsample that excluded participants who didn’t have data on APOE-4.

The results were similar to the main analysis, with the relative risk actually appearing even higher. However, researchers believe this was due to the smaller sample size and the higher loss of participants with microbleeds in the group without OSA compared to those in the OSA group.

Overall, study author Chol Shin, MD, PhD, Institute of Human Genomic Study, College of Medicine, Korea University, highlighted the following to Medical News Today about the study’s findings:

“From a Korean population, sleep studies and brain MRIs over eight years revealed that adults with moderate to severe obstructive sleep apnea (OSA) were more than twice as likely to develop microbleeds in the brain than those without sleep apnea.”

Timothy J. Barreiro, DO, MPH, professor of internal medicine, section chair, pulmonary, critical care, and sleep medicine, director of the pulmonary health & research center, who was not involved in the study, added the following:

“The finding is particularly strong because the association (Relative Risk, 2.14) persisted even after rigorous adjustment for key vascular and demographic confounders, including hypertension, diabetes, body mass index, and APOE−ϵ4 carrier status. This independence suggests that the mechanisms inherent to severe OSA, such as nocturnal hypoxia, oxidative stress, and inflammatory responses, may play a direct role in damaging the endothelium of the vasculature.”

Where the study may fall short

While insightful, this study also has limitations.

First, this research focused on the Korean population, which limits generalizability to other groups. Work from other ethnicities and countries can add more data. Work in younger participants may also be warranted, since this study focused on middle-aged and older adults. Less than 200 participants had moderate to severe OSA at baseline, so more data on this group may be warranted in the future. Only a small number of participants carried the APOE-ε4 allele, and even fewer had the same allele type from both parents or were homozygous for this allele, further limiting the research.

There were a fairly small number of microbleeds that occurred, and those that did occur were single microbleeds. Therefore, researchers were limited in the analysis they could conduct. Because researchers identified cerebral microbleeds using a less sensitive method, they recognize that they may have underestimated them.

Additionally, there was a difference between the scanners used for the baseline brain imaging and at the four-year follow-up and what was used for the eight-year follow-up, which could have impacted the results. Researchers chose to exclude participants from analysis, such as those with missing data, so they acknowledge the possible risk of selection bias.

Some data on covariates were based on participant reporting, such as data on exercise, which could be incorrect. Additionally, while some participants reported CPAP use, research did not have data on how often they were using it.

Researchers note that “a potential healthy cohort effect due to the long-term follow-up over two decades may limit the overall generalizability of our study findings.”

Future research can explore the underlying mechanisms or why obstructive sleep apnea has this impact on risk for cerebral microbleeds, such as how inflammation and oxidative stress may be involved.

What this means for people with sleep apnea

The research does imply that addressing OSA is important because of the risks associated with it. There’s the possibility of preventing far worse outcomes.

“Preventive measures for OSA and early diagnosis and treatment are necessary, not just to improve one’s sleep quality but also to prevent chances of developing brain microbleeds — a precursor of future stroke and dementia,” explained Shin.  

While more research on the benefits of obstructive sleep apnea treatment is needed, Stephen Carstensen, doctor of dental surgery and sleep expert, who was not involved in the study, also noted the following to Medical News Today:

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