by Fred Lane PhD
After years of resistance, “chemo brain” (aka post-chemotherapy cognitive impairment, chemotherapy-induced cognitive dysfunction, et al), is gaining recognition in mental health and allied professional fields. Nearly all cancer patients undergoing powerful chemotherapy report this disorder and many surgical patients experience some kind of memory problem. Maybe 15 or 20 per cent report chronic significant impairment (Silverman and Davidson, 2009). Additionally, some cholinesterase inhibiting drugs, ostensibly for the treatment of Alzheimer’s disease, have been linked to dangerous falls because of chemical interactions in the brain.
The symptoms are fairly consistent, particularly in high-functioning people who had a past history of successfully juggling complex and multiple demands: problems with memory, word retrieval, concentration, handling numbers, multi-tasking and setting priorities. Some of these signs are seen in early Alzheimer’s disease, except true Alzheimer’s patients might not be aware of the problem until someone draws their attention to it. Early intervention and prevention strategies are therefore important if we are to fully understand the problem and avoid the “do-nothing” misdiagnoses.
Equally important is the avoidance of unnecessary stress on the one hand and apathy on the other. Both can make the condition worse. It is very important to differentiate the potentially curable “chemo brain” disorder from one of the more malignant dementias, like Alzheimer’s disease.
But first, Alzheimer’s patients taking cholinesterase inhibiting drugs, such as Aricept (donepezil hydrochloride), Exelon (rivastigmine) and Reminyl (galantamine hydrobromide), might have yet another more serious chemotherapy-related problem. These specific drugs were all used in the treatment of mild to moderate dementia, but in July 2009 they were moved to the “do not use” category by Worst Pills Best Pills, a highly respected American pharmaceutical research group.
As well as the usual but comparatively less dangerous side effects like nausea, diarrhoea, muscle cramps and incontinence, these drugs might contribute to slow heart rhythms and particularly to sudden fainting (syncope) when sitting or standing,
Falls, bone fractures
Fainting spells are particularly dangerous. They lead to falls and bone fractures, according to a persuasive study involving 80,000 patients (Sudeep et al, 2009). Dangerous side effects might not be seen at first, but they can develop over time and many other drugs can interact to produce potentially dangerous behaviour. An increased proportion of these patients taking these drugs were hospitalised for pacemaker insertions. This low risk, but nevertheless invasive procedure might not be needed at all if the cholinesterase inhibiting medication is avoided in the first place.
The cholinesterase inhibitors’ efficacy is in doubt in that while they might seem to blunt some of the more florid symptoms of Alzheimer’s disease and briefly slow the progress of the disorder, these benefits, like nearly all of the other Alzheimer’s interventions over the past 50 years, disappear over time and make little or no difference to the ultimate outcome of the disease. On the other hand, the prestigious Mayo Clinic and some other respected groups are still recommending cholinesterase inhibitors for mild to moderate Alzheimer’s and suggest they may be taken even in conjunction with Namenda (memantine hydrochloride) for moderate to severe cases. “People with moderate Alzheimer’s may experience even better results by taking memantine along with a cholinesterase inhibitor,” said a July 2009 Mayo Clinic report.
Oddly, the medical researcher presenting the results of a 2003 investigation into Namenda data to the USA Federal Drug Administration (FDA) reported, “Only a small minority of patients treated with memantine showed even a minimal or moderate improvement, with no patients showing a marked improvement, and the most common response being no change,” (Mani, 2003).
Namenda, marketed in Europe since the 1980s and approved by the FDA in 2003, is claimed to moderate the activity of glutamate, a common brain messenger chemical linked to the over-activation of some brain receptors that contribute to the destruction of brain cells. At the time of its approval, it was the only drug approved by the FDA for use with severe Alzheimer’s patients. Nameda is also used at times in the treatment of acute pain and AIDS-related dementia.
Once more, however, Worst Pills Best Pills researchers allocate Nameda to the “do not use” category with Alzheimer’s disease because of its modest (if at all) proven efficacy and dangerous side effects. Further research seems warranted and we await eagerly the outcome of a study presently under way in Stanford University, California, testing the drug’s efficacy with Huntington’s disease patients.
Let’s return to the chemo brain question in cancer patients who have no other convincing dementia sign. Interestingly, the disorder may be most frequently seen during or after chemotherapy treatment for breast cancer, ovarian cancer, prostate cancer and other cancers of the reproductive system (Matsuda et al). If there has been no sign of cognitive impairment before chemotherapy, then confusion and difficulty completing a job, losing a car in a car park or difficulty adding numbers may be a first warning sign of a serious chemical reaction affecting the memory components of the brain.
Sitting down and saying, “I’m getting old, I have to accept this,” is absolutely the worst thing to do for any kind of memory impairment. Start with a regular written daily log of memory problems to quantify their quality and quantity. This serves two purposes. It helps your GP understand your problem and serves to quantify positive changes frequently missed by simple ancedotal reminiscence. That log becomes important hard evidence for a post-treatment “Attaboy” self-talk pat on the back, an important component of all cognitive-behavioural therapy.
Stopping medication might be enough to control some disorders, but this might be too dangerous or too late for problems arising from cancer medication or anaesthesia.
Silverman and Davidson recommend a smorgasbord of systematic and thoroughly tested cognitive behavioural therapy techniques such as prioritising tasks, developing routines, rehearsing responses to expected difficult situations, employing mnemonics and rhymes, using multiple senses, using notebooks, posting checklists in strategic places, using day planners, leaving messages for yourself, monitoring sleeping patterns, getting adequate rest and using cues like a saucepan on the TV to remind you of cooking on the stove. They strongly support the “use it or lose it” strategy.
Control your life
On the one hand, learn how to say “No” to those who want to overload you with routine work. On the other hand, keep your brain active, for instance with reading, crosswords, number puzzles and learning new skills.
Memory impairment is real. It does react positively to cognitive-behavioural interventions. Check it out. Give it a try.
Mani R.B. Food and Drug Administration – Final briefing document for advisory committee meeting – Efficacy review of memantine (Namenda), Aug 19, 2003: 15.
Matsuda T., T. Takayama, M. Tashiro, Y. Nakamura, Y. Ohashi, K. Shimozuma. Mild cognitive impairment after adjuvant chemotherapy in breast cancer patients – evaluation of appropriate research design and methodology to measure symptoms. Breast Cancer 12 (4), pp. 279–87. 2005.
Silverman D and I. Davidson. Your brain after chemo: A practical guide to lifting the fog and getting back your focus. Da Capo Press: Cambridge. 2009.
Sudeep S.G., G.M. Anderson, H.D. Fischer, C.M. Bell, P. Li, S.T. Normand and P.A. Rochon. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: A population-based cohort study. Archives of Internal Medicine 169(9), pp. 867-873. 2009.
Mayo Clinic. http://www.mayoclinic.com/healthj/alzheimers/AZ00015.
Worst Pills Best Pills. https://www.worstpills.org/public/page.cfm?op_id=49.