How might sleeping aids affect brain health? A mouse study aims
to shed some light on this matter.
- As many as 70 million people have consistent
sleeping issues.
- Not getting enough sleep each night can raise a
person’s risk for several health concerns, including cognitive decline and
dementia.
- For the first time a new study describes the
synchronized oscillations during sleep that power the brain’s glymphatic
system to help remove ‘waste’ associated with neurodegenerative diseases,
via a mouse model.
- Researchers also found that a commonly
prescribed sleep aid might suppress those oscillations, disrupting the
brain’s waste removal during sleep.
- Looking at all the possible factors that might
contribute to potential cognitive decline risk is important, particularly
as new research estimates that dementia risk the risk after the age of 55
among Americans has now more than doubled.
Although doctors recommend
that adults over the age of 18 get at least 7
hoursTrusted Source of quality sleep each
night, the most recent data suggest that many may face consistent sleep issues,
such as insomnia and sleep apnea.
Data from 2022 suggest
that, in the United States alone, 39% of adultsTrusted Source over
the age of 45 were not getting sufficient sleep.
Past studies report that
not getting enough sleep each night can increase a person’s risk for several
health concerns, including brain-related conditions, such as cognitive
declineTrusted Source and dementia.
“Sleep allows the brain to go offline, shut down
processing of the external world and focus on maintenance tasks, such as immune
surveillance and removal of waste,” Natalie Hauglund, PhD, a postdoctoral
fellow at the Universities of Copenhagen in Denmark, and Oxford in the United
Kingdom, explained to Medical News Today. “The
lack of sleep is associated with cognitive impairment and disease development.”
But could some sleep aids
also contribute to poorer brain health as we age? It is now more important than
ever to study all the possible factors that might contribute to cognitive
decline, particularly seeing that a new study published in Nature MedicineTrusted Source estimates
that dementia risk after the age of 55 among Americans has more than doubled,
compared to past figures.
Hauglund is the first
author of another study, which appears in the journal CellTrusted Source,
and that, for the first time, describes the synchronized oscillations during
sleep that power the brain’s glymphatic
system to help remove “waste” associated with neurodegenerative
diseases, via a mouse model.
The study also reports that the commonly prescribed
sleep aid zolpidemTrusted Source —
marketed under the name Ambien —
may suppress those oscillations, disrupting the brain’s waste removal during
sleep.
For this study,
researchers used various technologies to record brain activity while mice were
both awake and asleep.
Scientists observed that
slow synchronized oscillations of the neurotransmitter norepinephrine, along
with cerebral blood and cerebrospinal
fluid (CSF)Trusted Source,
combine during non-rapid eye movement (non-REM) sleep, essentially power the brain’s
waste-removing glymphatic system.
“Our brain is unique in
that it does not have lymphatic
vessels, which removes waste products such as dead cells and
bacteria from the rest of our body,” Maiken Nedergaard, MD, PhD, professor at the
Universities of Rochester and Copenhagen and lead author of this study told MNT.
“Instead, the brain uses
cerebrospinal fluid, a brain fluid that is produced inside the brain, to flush
the brain tissue and wash away unwanted molecules,” she explained.
“The cleaning system of the
brain is called the glymphatic system. Importantly, the glymphatic system is
only on during the deep part of sleep called non-REM sleep. This is because of
a neuromodulator called norepinephrine,
which during non-REM sleep is released in slow cycles roughly every 50
seconds.”
– Maiken Nedergaard, MD,
PhD
“Norepinephrine binds to
the muscle cells of the arteries, which makes them constrict,” Nedergaard told
us. “Therefore, the slow oscillation in norepinephrine concentration drives a
slow fluctuation in the diameter of the arteries and in the blood volume in the
brain.”
”This dynamic change in
blood volume works like a pump to transport cerebrospinal fluid along the
arteries towards the brain and through the brain tissue. Thus, norepinephrine
coordinates the synchronized constriction and dilation of the blood vessels
which drives the glymphatic system,” she detailed.
Researchers
also examined if sleep aids might replicate the natural
oscillations needed for glymphatic function. They focused their research on the
sedative zolpidem.
They discovered that
zolpidem appeared to halt norepinephrine oscillations, interrupting the
glymphatic system’s waste removal in the brain during sleep.
“Sleep aids may provide a
short-cut to sleep, but our study shows that the sleep you get with sleep
medication may lack the beneficial effects of natural, restorative sleep,”
Hauglund said. “Our findings underscore that sleep aids should only be used for
short periods of time and as a last resort.”
Nedergaard explained that:
“Sleep is crucial as it
gives the brain time to perform homeostatic housekeeping tasks such as waste
removal. On the contrary, sleep aids block the neuromodulators that drive the
waste removal system and prevent the brain [from] properly preparing for a new
day.”
MNT also
spoke with Clifford Segil, DO, a
neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about
this study.
According to Segil, who was not involved in the
recent research, “it is extremely unlikely the benefits of increased sleep which
occurs when patients use a sleep aid like zolpidem are outweighed by any
claimed potential adverse effect of this medication decreasing REM sleep, which
then in turn decreases brain neurotransmitter levels, [which] then in turn
decreases brain protein levels,”
“There are too many ‘in
turn’ claims to cause me any concern [that] there is any clinical significance
to the research,“ he told us. “Clinical neurologists like me are not concerned
[that] using zolpidem appropriately in elderly patients who can’t sleep will
cause dementia.”
Furthermore, he pointed
out: “In the year 2025, there remains no accepted response on why we sleep.
Different researchers make different claims and sometimes these are the same
and sometimes they are different. We know healthy sleep makes us healthy and
poor sleep makes us unhealthy.”
“For clinical neurologists
like me, it is challenging to agree that a sleeping medication will cause
dementia, and I would reassure my patients the benefits or a good night sleep
outweigh any claimed potential risk these can cause memory loss as you age or
dementia,” Segil added.
Finally, MNT spoke
with Peter G. Polos, MD, PhD, FCCP, FAASM,
an assistant professor of sleep medicine at the Hackensack Meridian
Neuroscience Institute at JFK University Medical Center in New Jersey, about
this research.
Polos, who was not involved
in the study, commented that he found the results intriguing.
“There is no doubt that the
interaction between the glymphatic system and various transmitters and waste
products in the brain can work in synchrony,” he said.
“This study suggests that
alterations in this tight balance have potential cellular and perhaps clinical
consequences. While fascinating, we must remind ourselves that this is an
animal study and, as is often the case, extrapolation of animal data to humans
must be done cautiously. Nonetheless, it does give clinicians a phenomenon that
is deserving of some discussion.”– Peter G. Polos, MD, PhD, FCCP, FAASM
“If
more work were to be done in this area, we certainly would like to see if
studies could assess the impact of sleep aids on human glymphatic flow,” Polos
continued. “This of course would require noninvasive techniques and perhaps
some advanced imaging. Such information, even if in small numbers, would be of benefit.”
“The interaction between
the brain, quality sleep, and overall health cannot be understated,” he added.
“The rhythmic nature of sleep and the regular
cycling of sleep stages have been well studied, We have learned much about the
effects of alterations in the brain and their impact on sleep, We do have much
more to learn and so we, as sleep physicians, fully support continued research
in the relationship between the brain, sleep, and overall health.”