From: drarwingnuttephd@gmail.com   
      
   Can General Anesthesia Trigger Dementia?   
   Scientists try to untangle the relationship between a temporary effect and a   
   permanent condition   
   October 23, 2014 |By Roni Jacobson   
   anesthesia   
      
      
   What do we know about the relationship between general anesthesia, which is   
   typically inhaled and completely knocks people unconscious, and dementia, a   
   permanent, debilitating condition?    
   Credit: Stefan Ray via flickr   
   Sanfra Anastine had surgery at age 42 and couldn't speak for about 12 hours   
   afterward. The next time she was operated on she was 56 and it took three   
   months for her speech to return. Now 61, Anastine says that she doesn't have   
   difficulty forming words    
   anymore but is still more forgetful than before her second surgery. She's   
   afraid of what will happen if she has to go under anesthesia again.   
      
   It is common to hear that an elderly patient "just isn't the same" after   
   surgery, says Roderic Eckenhoff, an anesthesiologist at the University of   
   Pennsylvania.* Many people wonder if anesthesia--which is designed to make   
   people groggy and temporarily    
   rob them of their mental faculties--is to blame. Elderly patients often   
   exhibit a condition called postoperative cognitive decline in which they   
   experience lapses in memory and attention, but it usually does not last for   
   more than a few weeks.   
      
   Most evidence suggests that receiving general anesthesia during the course of   
   surgery does not increase the likelihood of developing lasting dementia. Yet   
   it is clear something is going on: Recent experiments on animals and human   
   cells show that    
   anesthesia can increase the buildup of the proteins thought to underlie   
   Alzheimer's disease, especially in high doses.   
      
   So what do we know about the relationship between general anesthesia, which is   
   typically inhaled and completely knocks people unconscious, and dementia, a   
   permanent, debilitating condition?   
      
   Despite being a well-established component of modern medicine, much of how   
   anesthesia works is a mystery. Evidence indicates that drug molecules bind to   
   sites on the surface of neurons and deactivate different proteins important in   
   a wide range of    
   cognitive functions, including sleep, attention, learning and memory. Most   
   recently research has suggested that in addition to targeting specific areas   
   involved in sleep and arousal general anesthesia works by knocking out the   
   neural networks that enable    
   communication between brain regions.   
      
   Because anesthesia affects so many diverse brain processes and areas, some   
   researchers worry that it may have unforeseen consequences. The molecules in   
   anesthesia "can trigger other mechanisms that have nothing to do with   
   anesthesia itself," says Maria    
   Lioudyno, a neuroscientist at the University of California, Irvine. Including   
   "processes that may be linked to neurodegeneration."   
      
   At the cellular level, Lioudyno has found that anesthesia can set off a   
   chemical cascade triggering the release of microglia, immune cells normally   
   deployed to fight infections in the brain. When microglia are activated for   
   long periods of time they can    
   inflame brain tissue, which is thought to contribute to the cognitive problems   
   associated with Alzheimer's.   
      
   Recent research on animals has also shown that anesthesia can induce brain   
   changes like those thought to underlie dementia. In 2004 and 2007 studies, for   
   instance, Eckenhoff and his colleagues found that exposing mice to inhaled   
   anesthetics, especially    
   at high doses, accelerated the buildup and toxicity of amyloid beta, a protein   
   implicated in the development of Alzheimer's. Other studies have shown a   
   similar effect with tau, another Alzheimer's-linked protein.   
      
   These studies are very preliminary, Eckenhoff cautions. Humans are vastly more   
   complex than mice and just because something shows up in a petri dish does not   
   mean it leads to the development of Alzheimer's. Although changes are showing   
   up on the cellular    
   and tissue levels, "the effect on what we really care about--cognition,   
   memory, the ability to learn--seems to be really minimal," Eckenhoff says.   
      
   Furthermore, epidemiological evidence casts doubt on a link between receiving   
   anesthesia and developing dementia. In a 2013 Mayo Clinic study doctors   
   compared medical records of 900 people over 45 who had developed dementia with   
   a similar group who did    
   not develop the disorder and found that both received anesthesia at similar   
   rates, making it unlikely to be a risk factor.   
      
   But although anesthesia does not appear to increase the risk of developing   
   dementia, there is no denying that some people seem more deeply affected by it   
   than others. One possible explanation is that its effects may be amplified in   
   patients who are    
   already genetically predisposed to dementia or have other risk factors. "Human   
   beings come in many different sizes and have different preexisting conditions   
   that may put them at higher risk," says Robert Whittington,  professor of   
   clinical anesthesiology    
   at Columbia University Medical Center. Postoperative cognitive decline has   
   been found to be especially prevalent in patients who have had cardiac   
   surgery, for instance, as well as among people with diabetes and hypertension,   
   conditions which have also    
   been tied to Alzheimer's.   
      
   It is difficult to untangle the effects of anesthesia from those caused by the   
   operation itself, however. Surgery is a traumatic experience that is known to   
   provoke inflammation. Eckenhoff believes neuroinflammation from surgery rather   
   than anesthesia is    
   the true culprit in cognitive decline, which can "interact with pathology that   
   is sort of smoldering along in somebody with incipient Alzheimer's disease"   
   and accelerate it, he says. "We don't think that anesthesia and surgery   
   actually cause Alzheimer's    
   or cause dementia," he adds. "We think that it interacts with individual   
   vulnerabilities where if you're already predisposed to getting something like   
   this, this speeds it up."   
      
   Scientists are working on ways to identify populations that might be more   
   susceptible to dementia via biomarkers and other tests, and eventually hope to   
   use that information to make surgery safer for them. This could potentially   
   include smarter,    
   biologically targeted anesthetics, along with drugs to counteract the stress   
   involved in surgery. For instance, statins--commonly used to treat   
   cardiovascular disease--have been found to reduce cognitive decline in mice   
   when given before an operation.   
      
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)