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 Anesthesia and Cognitive Dysfunction 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Anesthesia and Cognitive Dysfunction
This press release is from Mass. General Hospital last week on isoflurane; it causes Alzheimer's-like changes in mammalian brains. Researchers mention an anesthetic that may be safer -- desflurane.


http://www.massgeneral.org/about/pressr ... px?id=1443

Massachusetts General Hospital Press Release
01/Mar/2012

Study reveals how anesthetic isoflurane induces Alzheimer's-like changes in mammalian brains

MGH researchers find desflurane may be safer anesthetic option for patients with Alzheimer's disease


The association of the inhaled anesthetic isoflurane with Alzheimer's-disease-like changes in mammalian brains may by caused by the drug's effects on mitochondria, the structures in which most cellular energy is produced. In a study that will appear in Annals of Neurology and has received early online release, Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory – a result not seen when another anesthetic, desflurane, was administered. They also found evidence that the two drugs have significantly different effects on mitochondrial function.

"These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria," says Yiying (Laura) Zhang, MD, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study's lead author. "This work needs to be confirmed in human studies, but it's looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer's patients."

Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer's, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period. In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer's-like changes – increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease – in the brains of mice. The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane's effects with those of desflurane, another common anesthetic that has not been associated with neuronal damage.

In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase. The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species – unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group. None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.

In another study by members of the same research team – appearing in the February issue of Anesthesia and Analgesia and published online in November – about a quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance. That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients – 15 in each treatment group – so its results need to be confirmed in significantly larger groups.

"Approximately 8.5 million Alzheimer's disease patients worldwide will need anesthesia and surgical care every year," notes Zhongcong Xie, MD, PhD, corresponding author of both studies and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine. "Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in anesthesia, neurology, geriatric medicine and other specialties. As the first step, we need to identify anesthetics that are less likely to contribute to Alzheimer's disease neuropathogenesis and cognitive dysfunction." Xie is an associate professor of Anesthesia at Harvard Medical School (HMS)

Additional co-authors of the Annals of Neurology study are Zhipeng Xu, MD, PhD, Hui Wang, MD, and Yuanlin Dong, MD, MGH Anesthesia; Rudolph Tanzi, PhD, MGH Neurology; Hai Ning Shi, DVM, PhD, MGH Pediatrics; Deborah Culley, MD, and Greg Crosby, MD, Brigham and Women's Hospital; and Edward Marcantonia, MD, MS, Beth Israel Deaconess Medical Center. The study was supported by grants from the National Institutes of Health, the American Geriatrics Society, the Alzheimer's Association and the Cure Alzheimer's Fund.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.


Mon Mar 05, 2012 5:42 pm
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Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Re: Anesthesia and Cognitive Dysfunction
Mass. General Hospital researchers were already sounding alarms about the (inhaled) anesthetic isoflurane back in 2007. There was a very good article on delirium associated with hospital stays in the Boston Globe on 2/12/07. (I posted the article elsewhere on the Forum back in 2007. Surprisingly, the link remains the same.)


http://www.boston.com/news/globe/health ... ?page=full

An end's beginning
More than half of all elderly hospitalized patients suffer severe confusion. Many ultimately decline into dementia. Are there common triggers to both?

By Alice Dembner, Globe Staff
The Boston Globe
February 12, 2007


Mon Mar 05, 2012 5:45 pm
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Joined: Fri Jan 15, 2010 9:33 pm
Posts: 3436
Location: Vermont
Post Re: Anesthesia and Cognitive Dysfunction
Thanks. I am facing rotator cuff surgery and my biggest fear is the anesthesia causing dementia issue. Glad you posted this - will talk with my dr. about it. Lynn

_________________
Lynn, daughter of 89 year old dad dx with possiblity of LBD, CBD, PSP, FTD, ALS, Vascular Dementia, AD, etc., died Nov. 30, 2010 after living in ALF for 18 months.


Wed Mar 14, 2012 9:59 am
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Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Re: Anesthesia and Cognitive Dysfunction
Interesting research from a Canadian, Portuguese, and American team was just published on how post-anesthesia dementia looks like Alzheimer's.

Here's a lay article (though still challenging reading):

http://www.newswise.com/articles/comput ... anesthesia

Here's a link to the research article:

http://www.plosone.org/article/info%3Ad ... ne.0037251

The lay article's final paragraph is:

Travis Craddock PhD, lead author on the study said: “The good news is that therapies aimed at microtubule stabilization may help in both Alzheimer’s and post-anesthetic dementias. Clinical trials are underway, or planned, for microtubule stabilizers Epothilone D, NAPVSIPQ, and the zinc ionophore PBT2, as well as brain ultrasound, shown in vitro to excite MT resonances and promote polymerization. However it’s done, ‘tightening the tubules’ may best treat dementia.”


FYI - Microtubules are not a problem in LB disease.

Robin


Thu Jun 28, 2012 11:35 am
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