||Researchers at the University
of Pennsylvania’s School of Medicine have discovered
that common inhaled anesthetics increase the number of amyloid
plaques in the brains of animals, which might accelerate the
onset of neurodegenerative diseases like Alzheimer’s.
||Researchers exposed “middle-aged” Alzheimer
mice to anesthetics at low to moderate concentrations for two
hours a day over a total of five days, not unusual for a clinical
||Compared to controls, the anesthesia did not appear to worsen
cognitive ability but it did accelerate amyloid beta aggregation
and plaque appearance.
||The researchers have reported their findings
in the March 7th online edition of Neurobiology of Aging.
(PHILADELPHIA) – Researchers at the University
of Pennsylvania School of Medicine have discovered
that common inhaled anesthetics increase
the number of amyloid plaques in
the brains of animals, which might accelerate the onset of neurodegenerative diseases
like Alzheimer’s. Roderic
Eckenhoff, MD, Vice Chair of Research
in the University of Pennsylvania’s Department of Anesthesia
and Critical Care, and his co-authors, report their findings
in the March 7th online edition of Neurobiology
Every year over 100 million people undergo surgery worldwide,
most under general
anesthesia with an inhaled drug. These drugs
clearly affect cognitive ability at least in the short term, but
the growing concern is that inhaled anesthetics may affect a person
well beyond the perioperative period, even permanently. Several
factors appear to play a role in this subtle loss of cognitive
ability, most notably age.
A specific effect of these drugs on dementias like Alzheimer’s
disease, though suspected for many years, has only been recently
supported by data. In 2003, Eckenhoff’s group showed that
the inhaled anesthetics enhance the aggregation and cytotoxicity
of the amyloid beta peptide. Just last month, a study reported
that these drugs also enhance the production of amyloid beta in
isolated cells. But these protein and cell culture studies are
a long way from showing that an effect occurs in vivo. This new
study provides the first evidence that the predicted effect occurs
“This animal study data suggests that we have to at least
consider the possibility that anesthetics accelerate certain neurodegenerative
disorders,” said Eckenhoff. “In the field of Alzheimer’s
research, most effort is focused on delaying, not curing the disease.
A delay in the onset of Alzheimer’s disease of only three
to five years would be considered a success. Therefore, if commonly
used drugs, like anesthetics, are accelerating this disorder, even
by a few years, then a similar success might follow even small
changes in the care of the operative patient.”
Mice don’t naturally get Alzheimer’s, so the animals
in this study were genetically engineered to express the human
protein responsible, called amyloid
beta. “These mice develop
a syndrome with many features of the human disease,” explains
Eckenhoff. Post-doctoral fellow and first author Shannon
Bianchi, MD, exposed “middle-aged” Alzheimer
mice to anesthetics at low to moderate concentrations for two hours
a day over a total of five days, not unusual for a clinical scenario.
The cognitive abilities of the mice were then analyzed using standard
behavioral tests, and their brains were examined for plaque and
“Compared to controls, the anesthesia did not appear to
worsen cognitive ability, which was already considerably compromised
at this age, but it did accelerate amyloid beta aggregation and
plaque appearance,” said corresponding author Maryellen
Eckenhoff, PhD. “We need to test whether anesthetic
at earlier, presymptomatic stages, might accelerate both cognitive
loss and plaque.” This is the main cause of concern because
a large fraction of clinical patients receiving inhaled anesthetics
during surgery are older, but presymptomatic individuals.
Are there anesthetics that do not accelerate plaque? “We
think so, but far more research is necessary to show this with
any confidence. We have to take this one step at a time – a
problem has still not been demonstrated in humans." It is
important to remember that this effect is likely to be subtle,
especially with brief surgical procedures, so the risk of not having
needed surgery may exceed any potential risk from this still unproven
effect. But this latest study adds a little urgency to the effort
to find out. “If inhaled anesthetics are contributing to
the rise and early onset of this devastating disease then we need
to know, and soon,” concludes Eckenhoff.
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