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From the Townsend Letter
April 2015

Integrative Treatment Considerations for Cancer–Treatment Related Cognitive Dysfunction
by Lise Alschuler, ND, FABNO
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Other Considerations
Research demonstrates that increasing oxygen to the brain can facilitate repair. Hyperbaric oxygen therapy (HBOT) administers pure oxygen in a pressurized chamber. HBOT has been primarily utilized for wound healing and decompression sickness, a hazard of scuba diving. It may also help repair brain damage. Preliminary research primarily involving traumatic brain injury demonstrates that HBOT induces neuroplasticity that repairs impaired brain function.32 The same neurological improvements in neuroplasticity were also seen in post stroke patients who utilized HBOT.33 Presently HBOT is not a recognized treatment for cancer-related cognitive dysfunction; however, the potential efficacy is intriguing.
   
Because chemo brain can significantly affect quality of life in some patients, referral to a psychotherapist may be beneficial. Cognitive behavior therapy (CBT) is a blend of cognitive and behavioral principles to help patients deal with dysfunctional cognitive processes and maladaptive behaviors. CBT can be especially effective in cases where depression and anxiety are present.34
   
In addition to psychotherapy and CBT, patients may benefit from speed of processing training as seen in brain fitness software programs. In one study, immediate and delayed memory was improved significantly compared with those who did not go through the brain fitness training.35
   
Finally, long-term meditation practitioners have thicker callosal regions, which leads to greater connectivity. 36 Brain mapping has in fact demonstrated enhanced structural connectivity in meditators compared with controls throughout the entire brain.37 Certainly, meditation would be a solid component of a self-care plan for individuals with chemo brain.

Conclusion
Presently, conventional medicine provides few options for patients who are experiencing chemo brain. After carefully considering potential underlying functional issues affected by chemotherapy – specifically brain connectivity, neurological inflammation, and nerve growth factor levels, integrative practitioners can work to rebuild greater cognitive function through a combination of targeted brain botanicals and nutrients such as lion's mane mushroom, acetyl-L-carnitine, citicoline, curcumin, and rosemary. Recommending HBOT, CBT, brain-building games, and meditation may also prove valuable for some of these patients. These treatments certainly do not represent an exhaustive list of cognitive-enhancing therapies. The most important take-away is to ask patients who have completed chemotherapy about their cognition. If cognitive challenges are present, integrative practitioners have a myriad of strategies to offer to these patients.

Notes
1.   Janelsins MC et al. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38(3):431–438.
2.   Koppelmans V, Breteler MM, Boogerd W, et al. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol. 2012;30(10):1080–1086.
3.   Hede K. Chemobrain is real but may need new name. J Natl Cancer Inst. 2008;100(3):162–163,169.
4.   Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7(3):192–201.
5.   Hede 2008. Op cit.
6.   Vardy J. Cognitive function and fatigue after diagnosis of colorectal cancer. Ann Oncol. Epub Sept. 11, 2014.
7.   Wefel JS et al. Chemobrain in breast carcinoma? A prologue. Cancer. 2004;101(3):466–475.
8.   Deprez S et al. Longitudinal assessment of chemotherapy-induced alterations in brain activation during multitasking and its relation with cognitive complaints. J Clin Oncol. 2014;32:2031–2038.
9.   Deprez S et al. Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol. 2012; 30:274–281.
10. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7(3):192–201.
11. Pusztai L et al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine. 2004;25(3):94–102.
12. Bermejo P et al. Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunol Lett. 2008;117(2):198–202.
13. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012;10:239.
14. Zimmer P. Post-chemotherapy cognitive impairment in patients with B-cell non-Hodgkin lymphoma: a first comprehensive approach to determine cognitive impairments after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or rituximab and bendamustine. Leuk Lymphoma. Epub 2014 Jun;5:1–6.
15. Li K et al. Protective effects of Hericium erinaceus mycelium and its isolated erinacine a against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. Int J Mol Sci. 2014;15(9):15073–15089.
16. Mori K et al. Improving effects of the mushroom Yamabushitake (Hericium ernaceus) on mild cognitive impairment: a double-blind, placebo-controlled clinical trial. Phytother Res. 2009;23(3):367–372.
17. Nagano M. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res. 2010;31(4):231–237.
18. Li G, Yu K, Li F, et al. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers. J Ethnopharmacol. 2014 Apr 28;153(2):521–530.
19. Pisano C et al. Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetyl-L-carnitine. Clin Cancer Res. 2003;9(15):5756–5767.
20. Vivoli E et al. Acetyl-L-carnitine increases artemin level and prevents neurotrophic factor alterations during neuropathy. Neuroscience. 2010;167(4):1168–1174.
21. Malaguarnera M et al. Acetyl-l-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial. Metab Brain Dis. 2011;26:281–289.
22. Cotroneo AM et al. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study. Clin Interv Aging. 2013;8:131–137.
23. McGlade E et al. Improved attentional performance following citicoline administration in healthy adult women. Food Nutr Sci. 2012;3:769–773.
24. Silveri MM et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR Biomed. 2008;21(10):1066–1075.
25. Mishra S, Palanivelu K. The effects of curcumin (turmeric) on Alzheimer's disease: an overview. Ann Indian Acad Neurol. 2008;11(1):13–19.
26. Nam SM, Choi JH, Yoo DY, et al. Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling. Med Food. 2014;Apr 8. 
27. Sanmukhani J et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014;28(4):579–585.
28. Mushtaq N et al. Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats. Cell Biochem Funct. 2014;32(3):287–293.
29. Moss M, Oliver L. Plasma 1,8-cineole correlates with cognitive performance following exposure to rosemary essential oil aroma. Ther Adv Psychopharmacol. 2012;2(3):103–113.
30. Moss M, Cook J, Wesness K, Duckett P. Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults. Int J Neurosci. 2003;113(1):15–38.
31. Barton DL et al. The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9. Support Care Cancer. November 13, 2012.
32. Boussi-Gross R et al. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury – randomized prospective trial. PLOS One. 2013;8(11):e7995.
33. Efrati S et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients – randomized, prospective trial. PLOS One. 2013;8(1):e53716.
34. Page AC, Hooke GR. Effectiveness of cognitive-behavioral therapy modified for inpatients with depression. ISRN Psychiatry. 2012;2012(2012).
35. Von Ah D et al. Advanced cognitive training for breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat. 2012;135(3):799–809.
36. Luders E et al. Bridging the hemispheres in meditation: thicker callosal regions and enhanced fractional anisotropy (FA) in long-term practitioners. Neuroimage. 2012;61(1):181–187.
37. Luders E et al. Enhanced brain connectivity in long-term meditation practitioners. Neuroimage. 2011;57(4):1308–1316.

Lise AlschulerDr. Lise Alschuler received her ND degree from Bastyr University in 1994 and is board certified in naturopathic oncology. She is past president of the American Association of Naturopathic Physicians and was a founding board member of the Oncology Association of Naturopathic Physicians. She is the coauthor of The Definitive Guide to Cancer: An Integrative Approach to Prevention, Treatment and Healing, now in its 3rd edition (Random House, 2010) and Five To Thrive: Your Cutting-Edge Cancer Prevention Plan (AIM Publishers, 2011). She, along with her coauthor Karolyn Gazella, have created www.FiveToThrivePlan.com, a multimedia website dedicated to sharing information about integrative cancer prevention and treatment. They also cohost a daily radio show, Five To Thrive Live! on www.w4CS.com, which provides listeners with tools for living healthier lives in the face of cancer.

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