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Omega-3s May Curb Post-Surgery Brain Fog
Some adults and children lose brain function after surgery; Omega-3-derived agents may help
7/7/2014By Craig Weatherby
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Image It’s normal to feel a bit “foggy” after major surgery.

This condition – called Postoperative Cognitive Dysfunction (POCD) – usually lifts within hours or days.

However, losses in memory and focus can last for weeks, months, or (more rarely) years following major surgery. 

POCD most often occurs after cardiac operations, but mental fog can result after any kind of major surgery.

Up to 40 percent of patients over 60 suffer POCD following major non-cardiac surgery, such as hip replacements. 

Surprisingly, POCD is as likely to occur after operations that involve regional anesthesia … suggesting that surgery itself, rather than drug-induced unconsciousness, is the main cause.

Risk factors for POCD
The risk of POCD rises with age, and patients aged 60 years or older run a significant risk of long-term cognitive problems.

POCD risk is affected by a number of factors:
  • Prior history of stroke
  • Duration of the operation
  • Success of the operation
  • Age – it’s more likely in people over 60
  • Drinking – it’s more likely in people who drink to excess
  • Declining mental functions (mild cognitive impairment) before surgery
While seniors run the greatest risk, some studies have linked use of general anesthesia in children to speech and learning difficulties (Flick RP et al. 2011; Wang X et al. 2014).

An Australian study found that one-third to one-half of all surgical patients suffered from POCD in the first week after surgery … a figure that dropped to 10 to 15 percent after three weeks, with almost all of those being older people (Evered L et al. 2011).

The Aussies found that one year after surgery, three-quarters of patients over 60 who’d had orthopedic or abdominal surgery still suffered from mild cognitive decline, while 11 percent suffered from severe mental decline.

Does surgery raises seniors’ dementia risk?
A recent animal study found that a common general anesthetic (propofol) produced brain changes linked to Alzheimer’s disease (Zhang Y et al. 2014).

There’s also growing human evidence that anesthetic drugs promote key biochemical mechanisms associated with Alzheimer's disease (Silverstein JH 2014).

Surgery and anesthetic drugs alike incite brain inflammation and may thereby promote the amyloid plaques linked to Alzheimer's disease.

However, the evidence is mixed when it comes to the likelihood for major surgery to cause or accelerate the decline toward dementia (Chen CW et al. 2014; Chen PL et al. 2014; Nadelson MR et al. 2014)

Most recently, British researchers concluded that the key factors determining the risk of POCD were the success of the surgery, the patient’s pre-operative cognitive health, and the patient’s post-operative stress levels.

They listed post-operative complications, ongoing inflammation, and chronic pain as preventable or treatable risk factors for POCD.

As the Brits wrote, major surgery does not usually cause lasting mental decline in people with good brain health, while cardiovascular surgery sometimes boosts brain function that was impaired by lack of circulation:
“When surgery is successful with minimal post-operative [problems], elderly patients can expect cognition to follow its pre-operative course. Furthermore, when surgery alleviates symptoms and enhances quality-of-life, postoperative cognitive improvement is a possible and desirable outcome.” (Nadelson MR et al. 2014)

Why would omega-3s help prevent POCD?
Most researchers believe that the body's inflammatory response to surgery plays a key part in promoting POCD.

Accordingly, surgeons sometimes prescribe anti-inflammatory drugs before operations ... and because both post-op problems can trigger inflammation, POCD risk is lower when doctors practice optimal pain and infection control.

As of this writing, researchers have not proven any pre- or post-surgery treatments for POCD consistently effective .

But hope may be on the horizon in the form of a fishy omega-3 fatty acid.

As we reported last year, aspirin stimulates production of potent inflammation-resolving (ending) substances called (appropriately) “resolvins”.

The body makes resolvins from DHA, the essential omega-3 fat found in virtually all human cells, especially brain cells … and in seafood.

DHA-derived resolvins may provide the basis for anti-inflammatory drugs more powerful than aspirin, yet far safer … see “Aspirin Mimics a Fishy Omega-3”. 

Swedish lab study finds omega-3-derived agent effective against POCD
According to Professor Lars Eriksson, who heads a Swedish group behind exciting new findings, “In the presence of essential omega-3 fatty acids, aspirin increases the body’s own production of resolvins like AT-RvD1, which promote resolution of inflammatory processes.” (KI 2013)

Last year, Eriksson’s research group – based at Sweden’s famed Karolinska Institute – found that aspirin protected rats from POCD by triggering the production of DHA-derived resolvins (Terrando N et al. 2013).

Dr. Eriksson’s group conducted a mouse study in which animals destined for surgery received a single dose of “aspirin-triggered resolvin D1” – AT-RvD1 for short – which the body makes from omega-3 DHA.

As expected, surgery triggered inflammation in the animals’ brains and caused memory impairment.

Encouragingly, the results showed that the DHA-derived resolvin protected the rodents’ brains from post-surgical memory problems.

And, even when it was given 24 hours after surgery, the omega-3-derived agent preserved the animals’ brain function.

“We report a novel role for [the omega-3-derived resolvin] AT-RvD1 in restoring memory dysfunction after surgery”, said Dr. Niccolo Terrando, who lead the study. “It was remarkable that AT-RvD1 displayed such unexpected effects on the central nervous system when administered at very low doses ...” (KI 2013)

As he said, “We hope to apply these therapies to prevent cognitive decline in at-risk surgical patients by translating our findings into patient care.” (KI 2013)

Dr. Terrando added an important point: “These molecules, aside from reversing inflammation, also promote healing and tissue regeneration that are of relevance to patient safety and recovery.”

Of course, these results need to be clinically tested in humans before we can know whether and how well they work in people … and we hope they soon will be.


Sources
  • Ballard C et al. Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. 15 Jun 2012; PLOS ONE 10.1371/journal.pone.0037410
  • Chen CW, Lin CC, Chen KB, Kuo YC, Li CY, Chung CJ. Increased risk of dementia in people with previous exposure to general anesthesia: a nationwide population-based case-control study. Alzheimers Dement. 2014 Mar;10(2):196-204. doi: 10.1016/j.jalz.2013.05.1766. Epub 2013 Jul 27.
  • Chen PL, Yang CW, Tseng YK, Sun WZ, Wang JL, Wang SJ, Oyang YJ, Fuh JL. Risk of dementia after anaesthesia and surgery. Br J Psychiatry. 2014 Mar;204(3):188-93. doi: 10.1192/bjp.bp.112.119610. Epub 2013 Jul 25.
  • Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg. 2011 May;112(5):1179-85. doi: 10.1213/ANE.0b013e318215217e. Epub 2011 Apr 7.
  • Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011 Nov;128(5):e1053-61. doi: 10.1542/peds.2011-0351. Epub 2011 Oct 3. Erratum in: Pediatrics. 2012 Mar;129(3):595.
  • International Society for the Study of Fatty Acids and Lipids (ISSFAL). Omega-3 Fats Critical to Brain Health After Traumatic Injury and Surgery. June 30, 2014. Accessed at http://www.prnewswire.co.uk/news-releases/omega-3-fats-critical-to-brain-health-after-traumatic-injury-and-surgery-265161181.html
  • Karolinska Institute (KI). Aspirin triggered resolvin protects against cognitive decline after surgery. February 26, 2014. Accessed at http://ki.se/en/news/aspirin-triggered-resolvin-protects-against-cognitive-decline-after-surgery
  • Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30.
  • Nadelson MR, Sanders RD, Avidan MS. Perioperative cognitive trajectory in adults. Br J Anaesth. 2014 Mar;112(3):440-51. doi: 10.1093/bja/aet420. Epub 2014 Jan 2. Review.
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  • Silverstein JH. Influence of anesthetics on Alzheimer's disease: biophysical, animal model, and clinical reports. J Alzheimers Dis. 2014;40(4):839-48. doi: 10.3233/JAD-130815.
  • Sprung J, Jankowski CJ, Roberts RO, Weingarten TN, Aguilar AL, Runkle KJ, Tucker AK, McLaren KC, Schroeder DR, Hanson AC, Knopman DS, Gurrieri C, Warner DO. Anesthesia and incident dementia: a population-based, nested, case-control study. Mayo Clin Proc. 2013 Jun;88(6):552-61. doi: 10.1016/j.mayocp.2013.01.024. Epub 2013 May 1.
  • Terrando N, Gómez-Galán M, Yang T, Carlström M, Gustavsson D, Harding RE, Lindskog M, Eriksson LI. Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. FASEB J. 2013 Sep;27(9):3564-71. doi: 10.1096/fj.13-230276. Epub 2013 May 24.
  • Wang X, Xu Z, Miao CH. Current clinical evidence on the effect of general anesthesia on neurodevelopment in children: an updated systematic review with meta-regression. PLoS One. 2014 Jan 20;9(1):e85760. doi: 10.1371/journal.pone.0085760. eCollection 2014.
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