Poor Sleep Related to Cerebrovascular Pathology in Elderly Adults

An autopsy study has established a link between sleep fragmentation and quantitative measures of cerebrovascular pathology in older people, but the direction of the relationship remains uncertain.

“Although based on this study alone, we cannot know for sure that sleep fragmentation contributes to brain blood-vessel damage and infarct pathology as opposed to vice versa, our data are consistent with this hypothesis and add to the growing body of evidence suggesting that sleep quality is linked to brain injury in older persons,” study author Andrew Lim, MD, of Sunnybrook Health Sciences Center (Toronto, Canada), told TCTMD in an email.Poor Sleep Related to Cerebrovascular Pathology in Elderly Adults

In prior research, his team has shown that sleep fragmentation is associated with dementia and cognitive decline in old age, but the mechanisms have not been established. Because experimental data have suggested that poor sleep may lead to impaired vascular health, Lim and his colleagues looked for relationships between sleep fragmentation and various types of brain injury.

The study, which was published online this week in Stroke, included 315 deceased individuals (mean age at death 90.4 years; 70% women) who participated in the Rush Memory and Aging Project. Sleep fragmentation measured by actigraphy was related to the severity of arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy as well as to the number of macroscopic and microscopic pathological infarcts assessed by structured brain autopsy. Overall, 61% of people had at least 1 moderate-to-severe vascular pathology.

A 1-SD increase in sleep fragmentation was associated with more severe arteriolosclerosis (OR 1.27; 95% CI 1.02-1.59) and more subcortical macroscopic infarcts (OR 1.31; 95% CI 1.01-1.68). Both relationships were independent of potential confounders, including established cardiovascular risk factors and comorbidities.

Sleep disruption was not related to the severity of atherosclerosis or amyloid angiopathy or to other types of infarcts or clinically evident strokes.

Uncertainty About Potential Mechanisms

There are 3 possible explanations for the findings, according to the authors: cerebrovascular pathology causes sleep fragmentation, sleep disruption causes brain injury, or an unmeasured variable predisposes to both.

Arguing against the first possibility is the fact that “the hypothalamus and other sleep centers represent a tiny volume of the brain and hypothalamic infarction is unusual because of its rich blood supply,” the authors explain. “Moreover, although individuals with clinical stroke symptoms should be the most likely to have stroke-induced sleep fragmentation, the associations were independent of clinically evident stroke.”

In support of the possibility that sleep fragmentation causes brain injury, “other forms of sleep disruption are associated with physiological risk factors for cerebrovascular pathology, including diurnal and nocturnal hypertension and abnormal glucose processing, among others…,” they say.

“Further work is needed to clarify whether these are consequences or causes of sleep fragmentation, the role of specific contributors to sleep fragmentation (eg, sleep apnea), and underlying biological mechanisms,” they conclude.

Lim ASP, Yu L, Schneider JA, et al. Sleep fragmentation, cerebral arteriolosclerosis, and brain infarct pathology in community-dwelling older people. Stroke. 2016;Epub ahead of print.

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  • The study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario, and the NIH.
  • Lim reports no relevant conflicts of interest.

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