Researchers from the University of Toronto, Canada; Columbia University, New York, NY; and Rush University, Chicago, IL have linked aging of particular cells in the brain (microglia) with disrupted sleep patterns (sleep fragmentation).

Kaneshwaran et al. (2019)

Disrupted sleep patterns (sleep fragmentation) associated with aging, along with dementia and cognitive decline in older adults.  The underlying physiological mechanisms causing disrupted sleep patterns (sleep fragmentation) and associated problems with cognition have previously remained unclear.  In rodents, disrupted sleep patterns (sleep fragmentation) caused activation of particular cells in the brain (microglia). Microglia constituted the purported immune system of the central nervous system (brain and spinal column).  Interestingly, suppression of the microglial response in these rodents improved cognition.

Scientists lacked data on this topic in humans. This caused some concern as global prevalence of dementia with subsequent disrupted sleep patterns (sleep fragmentation) is approximately 35.6 million people, and scientists believe the prevalence will double in the next 20 years. Thus, this team of neuroscientists embarked on a study measuring gene expression levels, shape of microglia (morphology), and levels of activity during sleep. These neuroscientists wanted to test whether an association existed between higher levels of disrupted sleep patterns (sleep fragmentation) and activated microglia as measured with gene expression and cell shape (morphology) of microglia.

In order to test for an association, the team recruited 685 adults older than 65 years of age, 265 of which had Alzheimer’s dementia.  This team of neuroscience researchers measured disrupted sleep patterns (sleep fragmentation) using actigraphy, a watch-like device that measured rest/activity cycles.  The neuroscientists then measured gene expression levels using a method called RNA sequencing. After performing statistical analyses, the researchers found an association between expression of genes from aged microglia and disrupted sleep patterns (sleep fragmentation).  The association remained with and without Alzheimer’s dementia or other brain pathology.

The next step of this study sought to see if an association existed between expression of genes from aged microglia and microglia in an activated state (microglia in activated states clean up or repair dead or dying neurons) as measured with observation of microglia cell shape (morphology).  The analyses run found an association between expression of genes from aged microglia and microglia in an activated state with disrupted sleep patterns (sleep fragmentation). Thus, the team speculated disrupted sleep patterns (sleep fragmentation) mediated expression of genes associated with aged microglia which become activated to clean up or repair dead or dying neurons.  This sequence may have facilitated difficulties related to cognition through aging.

The three possibilities that this study provided evidence for included microglia aging and activation could lead to sleep fragmentation, sleep fragmentation could lead to microglia aging and activation, or other changes like dementia-related brain pathologies may cause both.  Thus, the premise that this study supported related to greater levels of disrupted sleep patterns (sleep fragmentation) in older adults associating with higher expression of genes from aged microglia and with microglia in their activated state as measured with cell shape (morphology).  The sequence of causation remained uncertain.

Considering the data from this study, the possibility of disrupted sleep patterns (sleep fragmentation) contributing to microglia aging and activation persisted.  The association which this study makes may allow researchers to explore mechanisms involved in disrupted sleep patterns (sleep fragmentation) with age, cognitive decline, and dementia in older adults.  If the association was true, it “suggests that targeting microglia aging and/or associated activation may improve cognition in the context of sleep fragmentation,” according to this team of neuroscientists.  This topic will require further experimentation, though. First, future experiments will need to confirm that treating disrupted sleep patterns (sleep fragmentation) will affect whether microglia are activated in humans.  Next, experiments will need to also confirm that treating microglia biology has effects on cognition in older adults. For instance, in rats that undergo sleep deprivation, inhibiting microglia activation with medicine (minocycline) improves a type of memory (spatial memory).  Limited evidence in humans with disrupted sleep patterns (sleep fragmentation) showed whether similar pharmacological manipulations of microglia biology had these effects. Future research on this topic will require that these effects are validated in humans before proceeding to clinical trials.  Last, the study only examined older adults; and future studies in younger people will show whether these findings generalize to younger populations.