HIGHER levels of sleep fragmentation in older adults are linked to increased expression of specific vascular cell genes and a faster rate of cognitive decline, new research has revealed. The study identifies M-pericytes, a blood vessel cell subtype, as a potential mechanistic bridge between disrupted sleep and the development of dementia.
Sleep disturbances are known to be common in later life and frequently precede cognitive decline and dementia, yet the biological links have remained unclear. Researchers analysed brain tissue samples and extensive clinical assessments from the Religious Orders Study and Rush Memory and Aging Project cohorts, involving a total of 1,092 adults for the dorsolateral prefrontal cortex and 495 for the lateral orbitofrontal cortex. Using recent advances in single-nucleus RNA sequencing, they profiled two distinct pericyte subtypes: extracellular matrix protein-expressing M-pericytes and solute carrier-expressing T-pericytes. By quantifying the expression of marker genes for these cell types in post-mortem brain tissue and linking this to data from yearly cognitive assessments and sleep analysis via wrist-actigraphy, the researchers discovered that greater sleep fragmentation was consistently associated with heightened expression of M-pericyte genes in both brain regions examined (P = 0.024 in prefrontal cortex; P = 0.02 in orbitofrontal cortex). Furthermore, higher M-pericyte marker gene expression was significantly related to steeper decline in global cognitive function in the ten years before death (P = 0.014 in prefrontal cortex; P = 0.0044 in orbitofrontal cortex). No such associations were found for T-pericyte marker genes, nor did these genetic relationships appear in participants with more consolidated sleep.
The findings suggest that changes in M-pericyte biology, possibly linked to blood–brain barrier integrity and vascular health, may help explain how sleep disruption promotes cognitive decline and dementia onset in ageing populations. This research also encourages more frequent screening for sleep problems in patients with established cognitive impairment, highlighting sleep management as a modifiable contributor to long-term brain health.
Reference
Hamid M et al. Sleep, pericyte subtypes and cognitive decline in adults with and without Alzheimer’s disease. Brain. 2025;awaf161.
