The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 14 No. 1 • February 2011

Post-Operative Cognitive Decline
Associated with a Cytokine Cascade Triggered
by Tumor Necrosis-Factor-Alpha

Post-operative cognitive decline has been for many years a little known (by potential surgical patients) risk of operations. It is particularly common following open heart surgery, such as bypasses and opening blocked arteries with balloons. We had a good friend who had a heart transplant and was reported by those living in close proximity to him to have had a mental decline afterward from which he never recovered; he died a couple of years later.

A new paper1 reports on mechanisms underlying postoperative cognitive decline. As the authors point out, “[c]ritical illness and postoperative recovery are often associated with cognitive decline, including memory dysfunction, especially in the elderly …” The incidence of postoperative delirium reportedly ranges from “28 to 92% in hospitalized medical patients, depending on age, patient comorbidity, and the type of surgery …” though this acute confusion state is said to be typically limited in duration and potentially reversible. However, postoperative cognitive dysfunction is a longer lasting type of damage detected through a battery of neuropsychological tests. “After major noncardiac surgery, POCD [post-operative cognitive dysfunction] occurs in 7 to 26% of patients, and is independently associated with poor short-term and long-term outcomes, including an increased risk of mortality, inability to cope independently, premature unemployment, and possible permanent dementia.” The authors used a mouse model of orthopedic surgery to search for underlying immune and inflammatory mechanisms for this serious problem.

The researchers report that following surgery under general anesthesia, TNF-alpha (tumor necrosis factor alpha, a major inflammatory cytokine) was the first cytokine to be released and peaked at 30 minutes after surgery. In contrast, they note, other important proinflammatory cytokines such as IL-1beta and IL-6 were not detected until 6 hours postoperatively.

Moreover, the authors found that preoperative administration of a TNF-alpha antibody “effectively reduced the amount of systemic IL-1beta both at 6 and 24 hours following surgery.” Administering the TNF-alpha antibody 1 hour AFTER surgery had no effect. Although the inflammatory cytokine IL-1beta at low levels is important for hippocampal learning and memory, high levels are reported to interfere with long-term potentiation and synaptic plasticity.1

The authors note that: “Therapy with TNF-alpha inhibitors is clinically well established and already offers beneficial effects in inflammatory conditions, such as rheumatoid arthritis, Crohn’s disease, and ankylosing spondylitis, and may thus be useful for the prevention of postoperative cognitive decline in susceptible individuals.”

Natural products that attenuate the effects of TNF-alpha include quercetin2 (as contained, for example, in our high potency antioxidants, multivitamin, multimineral formulation, the herbal Cat’s Claw,3 xanthohumol (as found in hops),4 fish oil5 (as is found in our premium blend of omega-3 fatty acids derived from coldwater fish, highly concentrated and purified), and N-acetylcysteine.6


  1. Terrando et al. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 107(47):20518-22 (2010).
  2. Chuang et al. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-alpha-mediated inflammation and insulin resistance in primary human adipocytes. Am J Clin Nutr 92:1511-21 (2010).
  3. Sandoval et al. Cat’s Claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 29(1):71-8 (2000).
  4. Lupinacci et al. Xanthohumol from hop (Humulus lupulus L.) is an efficient inhibitor of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha release in LPS-stimulated RAW 264.7 mouse macrophages and U937 human monocytes. J Agric Food Chem 57:7274-81 (2009).
  5. Grimble et al. The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 76:454-9 (2002).
  6. Muscari et al. Long-term treatment with N-acetylcysteine, but not caloric restriction, protects mesenchymal stem cells of aged rats against tumor necrosis factor-induced death. Exp Gerontol 41:800-4 (2006).

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