Sleep Fragmentation Linked to Cerebrovascular Pathology

Pauline Anderson

January 14, 2016

Researchers have found an association between greater sleep fragmentation, defined as interruption of sustained sleep by repeated awakenings, and arteriosclerosis and subcortical infarcts in older adults.

"Although it's too early to say for sure that improving sleep will prevent damage to brain blood vessels, this study adds to the growing body of evidence that this may be the case, and provides another reason to get a good night's sleep," said lead author Andrew Lim, MD, neurologist, Sunnybrook Health Sciences Centre, and assistant professor, neurology, University of Toronto, Ontario, Canada.

The study was published online January 14 in Stroke.

The analysis included 315 autopsied individuals from the Rush Memory and Aging Project, a community-based cohort study of aging with brain donation upon death. The mean age of participants was 90.4 years; 70% were female.

Every 2 years, participants in the study wore actigraphs, wrist-watch like accelerometers, for up to 10 days. To separate sleep from awakenings, researchers used algorithms that correlate well with polysomnographic measures of fragmentation, including the arousal index, and sleep efficiency.

All participants had at least one actigraphic recording (the average was 3). Researchers then averaged all measurements.

More than a quarter of participants (29%) had a clinical stroke and 61% had at least one moderate to severe vascular pathology.

Severe Arteriosclerosis

The researchers found that each standard deviation (SD) higher sleep fragmentation was associated with an almost 30% higher odds of more severe arteriosclerosis (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.02 - 1.59; P = .03).

Sleep fragmentation was not significantly associated with atherosclerosis or amyloid angiopathy.

Each SD higher sleep fragmentation was also associated with a greater than 30% higher odds of having more subcortical macroscopic infarcts (OR, 1.31; 95% CI, 1.01 - 1.68; P = .04). Sleep fragmentation was not associated with cortical macroscopic infarcts, microscopic infarcts, or clinically evident strokes.

Adjusting for arteriosclerosis only changed the association between sleep fragmentation and subcortical infarcts by less than 5%, indicating that arteriosclerosis does not account for this association, said the authors.

The associations remained significant after adjustment for date of actigraphy and time of autopsy, and total daily rest and activity. The associations also didn't change significantly after factoring in other potential confounders, including cardiovascular risk factors and diseases, Alzheimer's pathology, pain, depression, and heart failure.

"For the most part, these other diseases played at most a minimal role in the association between sleep fragmentation and cerebrovascular pathology," commented Dr Lim.

According to the authors, the results could be interpreted in many ways: Cerebrovascular pathology causes sleep fragmentation, an unmeasured variable produces both sleep fragmentation and cerebrovascular pathology, or sleep fragmentation contributes to cerebrovascular pathology.

The results are consistent with a growing body of data suggesting that the last interpretation might be the most likely, Dr Lim told Medscape Medical News. "Although our study could not tell for certain the direction of causation, when considered in the context of the experimental evidence, we think it's plausible that sleep fragmentation may contribute to blood vessel damage."

Although actigraphy correlates strongly with polysomnography, it does not directly measure brain electric activity and does not distinguish between causes of sleep fragmentation. The study did not measure sleep apnea, one of the most common — and treatable — causes of sleep fragmentation in older adults.

Sleep fragmentation can be reduced by identifying and treating sleep disorders, including sleep apnea, and avoiding environmental and social causes of sleep disruption, such as excess noise and light, and irregular sleep patterns, said Dr Lim.

But at this point, he said, there's not enough evidence to suggest that patients try to prevent cerebrovascular pathology by treating fragmented sleep through sleep aids.

Stronger Wording

Commenting on the study for Medscape Medical News, Brian Silver, MD, associate professor, neurology, Alpert Medical School, Brown University, and director, Comprehensive Stroke Center, Rhode Island Hospital, Providence, said that although the authors were careful not to identify sleep apnea as the cause of sleep fragmentation, "that's more likely than not the situation."

He pointed to a recent study (Sleep Med. 2015;16:1198-1203) that showed almost 80% of patients with ischemic stroke had obstructive sleep apnea verified by polysomnography.

"The implication is that if we treat the sleep apnea, we would then reduce the likelihood of a second stroke; but that remains to be proven," said Dr Silver.

Recent guidelines suggest that clinicians consider ordering sleep apnea tests in patients who have had an ischemic stroke. "I have a feeling that as more data come out, the guideline is going to be more strongly worded," said Dr Silver.

That's because mounting evidence suggests that sleep apnea is causing the stroke, or at least contributing to it, rather than the stroke causing sleep apnea, or a third factor contributing to both, said Dr Silver.

There's no correlation, he explained, between regions of the brain affected by stroke and the likelihood of having sleep apnea. "You can't correlate brain regions with sleep apnea, so that suggests that it's not the brain that's causing the sleep apnea; it's the sleep apnea that's causing the stroke, and it can occur anywhere in the brain."

The new study contributes to the evidence, said Dr Silver. "It's saying that these are the pathological changes that we now see — that there's arteriosclerosis, and subcortical disease."

But because other research found associations between sleep disruptions and cortical strokes while this new study did not, "more work needs to be done in terms of how the relationship exists and to what extent it exists," said Dr Silver.

The study was funded by National Institutes of Health, the Heart and Stroke Foundation of Ontario, and the Canadian Institutes of Health Research. Dr Lim has disclosed no relevant financial relationships.

Stroke. Published online January 14, 2016. Abstract

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