(NaturalNews) Evidence continues to emerge that general anesthetics commonly used in surgery may actually produce some of the brain changes that lead to Alzheimer's disease.
Researchers have known for many years that certain patients experience dementia-like symptoms following surgery. In 2007, a team of researchers from Massachusetts General Hospital provided some of the first evidence directly linking anesthetics to these symptoms. When the researchers applied the common anesthetic gas isoflurane to nerve cells in the laboratory, levels of the enzymes beta-secretase (BACE) and gamma-secretase both increased, as did levels of the protein caspase.
BACE and gamma-secretase, in turn, are known to damage healthy amyloid precursor proteins (APPs) in the brain, breaking them into the abnormal alpha-beta proteins that accumulate during Alzheimer's disease. In the absence of BACE and gamma-secretase, an enzyme called alpha-secretase instead transforms APPs into a different, non-toxic protein.
These findings imply that the anesthetic isoflurane starts a chemical cascade that may lead to the accumulation of alpha-beta proteins and the development of Alzheimer's. The elevated levels of caspase further indicate increased cell death.
Effects confirmed in living model
In order to determine whether the same effect occurs in living mammals, the same research team exposed mice to isoflurane gas, in a study published in the Annals of Neurology in 2008. The mice were given a dose similar to what humans would receive prior to surgery, and their brains were examined at 2, 6, 12 and 24 hours after exposure.
At 6 hours, levels of caspase were elevated and BACE levels had slightly increased. By 12 hours, caspase levels remained elevated and BACE levels had increased further. At 24 hours, caspase levels had returned to normal, but levels of BACE were four times higher than normal, and amyloid-beta levels had also risen. None of these changes were observed in a control group.
"These are the first in vivo results indicating that isoflurane can set off a time-dependent cascade inducing apoptosis [cell death] and enhanced levels of the Alzheimer's-associated proteins BACE and A-beta," lead author Zhongcong Xie, MD, PhD, said.
"[I]t's looking like isoflurane may not be the best anesthesia to use for patients who already have higher A-beta levels, such as the elderly and Alzheimer's patients."
Evidence in human tests
Studies in humans also suggest a link between anesthesia and Alzheimer's development. One study found that, among people aged 80 years and older, Alzheimer's risk was directly correlated with exposure to general anesthesia. Another found a direct relationship between a greater exposure to general and spinal anesthesia before the age of 50 and a younger age of Alzheimer's onset.
A study conducted by researchers from the University of Pennsylvania and published in the journal Anesthesiology in 2011 further strengthened the case. Researchers collected samples of cerebral spinal fluid from 11 people about to undergo a routine endoscopic nasal surgery, then collected a further four samples at regular intervals after the surgery. They found that, six hours after surgery, levels of the Alzheimer's biomarker "tau protein" were significantly elevated in cerebral spinal fluid. Other biomarkers of inflammation and injury also increased.
High tau protein levels are considered a warning sign of Alzheimer's disease.
Participants exposed to the common inhaled anesthetic sevoflurane experienced the greatest increase in inflammatory biomarkers, compared with patients given other anesthetics.
"We have long sought a clearer picture of the true impact of anesthesia and surgery on the central nervous system," study author Dr. Roderic Eckenhoff said.
"Although not definitive, this human biomarker study gives some credibility to the notion that anesthesia and surgery produce an inflammatory insult on the brain and accelerate chronic neurodegenerative diseases like Alzheimer's."