HMN 2025: How Disrupted sleep damages blood vessels in brain and may increase dementia risk

A new study reveals that fragmented sleep causes cellular damage to the brain’s blood vessels, providing further evidence to suggest that sleep disruption predisposes the brain to dementia.

The research, published in the journal Brain, is the first to offer cellular and molecular evidence that sleep disruption directly causes damage to brain blood vessels and blood flow.

“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,” said Andrew Lim, principal investigator of the study and a sleep neurologist and scientist at Sunnybrook Health Sciences Centre.

“This in turn was associated with a more rapid decline in cognitive function in the decade leading up to their death.”

The researchers applied wearable smartwatch-like sensors to the research subjects—more than 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 Lim, who is also an associate professor in the department of medicine in the University of Toronto’s Temerty Faculty of Medicine.

“However, we didn’t have sufficient evidence behind the mechanisms underlying these links, until now.”

The study’s findings 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
• 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 study raises the possibility that changes in pericytes may be a mechanism linking sleep fragmentation with small vessel disease and cognitive decline,” says Lim.

If confirmed in clinical trials of sleep interventions with pericyte biomarker outcomes, Lim adds, “it would highlight that sleep interventions may be an effective means to alter human small vessel biology and cognitive decline, and also raise 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.”