New Sunnybrook-led research shows for the first time that fragmented sleep causes damage at the cellular level to the brain’s blood vessels, providing further evidence to suggest sleep disruption predisposes the brain to dementia.
“We found that individuals who had more fragmented sleep – such as sleeping restlessly and waking up a lot at night – had a change in their balance of pericytes – a brain blood vessel cell that plays an important role in regulating brain blood flow and the entry and exit of substances between the blood and the brain,” says Dr. Andrew Lim, principal investigator of the study and a sleep neurologist and scientist at Sunnybrook Health Sciences Centre. “This in turn was associated with more rapid decline in cognitive function in the decade leading up to their death.”
Published in the July 14 issue of Brain, the researchers applied wearable smartwatch-like sensors to the research subjects – over 600 older adults – to measure their sleep and used new gene sequencing technologies to measure levels of pericytes in the brain. The research participants subsequently passed away and donated their brains for analysis.
“We know that in some individuals, sleep disruption can precede the onset of cognitive impairment by years, with emerging evidence suggesting a bidirectional link between sleep disruption and Alzheimer’s disease,” adds Dr. Andrew Lim, also an associate professor in the Temerty Faculty of Medicine at University of Toronto. “However, we didn’t have sufficient evidence behind the mechanisms underlying these links, until now.”
The results suggest:
- Sleep fragmentation may be an important factor leading to brain blood vessel injury;
- Pericytes may be particularly important in mediating these effects;
- Targeting sleep fragmentation may be a means of improving brain vascular health, and
- Targeting pericytes may be a mechanism of preventing the deleterious effects of sleep fragmentation on brain blood flow and subsequently on Alzheimer’s disease and other dementias.
This is the first time that research has provided evidence at the cellular and molecular level that sleep disruption directly causes damage to brain blood vessels and blood flow, and in turn providing another mechanism that could contribute to the development of dementia.
“This study raises the possibility that changes in pericytes may be a mechanism linking sleep fragmentation with small vessel disease and cognitive decline,” says Dr. Andrew Lim. “If confirmed in clinical trials of sleep interventions with pericyte biomarker outcomes, it would highlight that sleep interventions may be an effective means to alter human small vessel biology and cognitive decline, and it also raises the possibility that aggressive treatment of other risk factors for cerebral small vessel disease may help prevent the deleterious impact of sleep fragmentation on small vessel biology.”