08:42am Sunday 20 October 2019

Cancer therapy and “chemobrain”

After chemotherapy many cancer patients report lapses of memory, difficulties in concentrating, and other cognitive problems. Many studies have indeed found cognitive compromise associated with cancer and cancer therapy. The deficits are usually mild, and only a subset of patients is affected. However, it has been repeatedly observed that the subjective cognitive problems are not related to objective assessments of cognitive function. Patients who complain of “chemobrain” generally do no worse (and no better) than others in neuropsychological tests of memory or concentration. At LMU Munich, this discrepancy has now been investigated in a study with over 100 breast cancer patients. The researchers included various factors in the analysis that might mask an underlying association between self-perceived and objectively assessed cognitive performance. They also investigated whether or not objectively assessed changes of cognitive performance are reflected in the patients’ self-reports. Nevertheless, subjective and objective evaluations of cognitive function were not related, and changes of test scores were not mirrored in self-reports. Patients who reported cognitive problems were more likely to be depressive and had higher levels of the personality trait Negative Affectivity, i.e., the disposition to experience negative emotional states. “Obviously, patients generally don’t notice the subtle neuropsychological compromise that has been detected in many studies”, says Dr. Kerstin Hermelink from the Department of Gynecology and Obstetrics of LMU Munich, the principal investigator or the study. “For the most part, complaints of ‘chemobrain’ seem to be pessimistic self-appraisals of cognitive functioning that are induced by depression and negative affectivity, regardless of whether or not neuropsychological compromise is actually present.” (Psycho-Oncology online, 5 February 2010)

As treatments become more effective, the number of cancer survivors continues to increase. After a period of intensive and often very distressing therapy, they reassume their everyday lives. At this point, the expectations of the patients themselves and the people around them are often rather great. Performance is assumed to return rapidly to its previous level, allowing the survivors once again to fulfil their accustomed roles at work and at home. However, many survivors fail to complete this transition successfully, even when their physical health has been restored. They are under the impression that they have become forgetful and are easily distracted, take longer to get things done, and often capitulate in the face of even minor problems. They notice odd mistakes and instances of confusion. In short, they seem to be less mentally acute than before their illness. Most patients attribute these perceived changes to the chemotherapy and talk of “chemobrain”.

Scientists have confirmed this picture. Cognitive compromise, such as mild deficits in memory, concentration and problem-solving, has often been demonstrated in subsets of cancer patients. However, in virtually all studies to the subject, subjectively perceived and objectively assessed cognitive dysfunction has not been found in the same patients –  the group of patients who feel cognitively impaired is different from the group of patients who show impairment in cognitive tests, and the overlap of the two groups doesn’t seem to be greater than a chance overlap. This puzzling observation has been made on patients who have had different types of cancer and different treatments. It has often been ‘explained away’ by arguing that the neuropsychological tests fail to reproduce everyday tasks or are insufficiently sensitive to capture the deficits reported by patients. Actually, these tests do detect cancer-related cognitive impairment, but in the ‘wrong’ patients — that is, not necessarily in those who complain of cognitive decline.

A team of researchers led by Dr. Kerstin Hermelink from the Department of Gynecology and Obstetrics of Ludwig-Maximilians-Universität (LMU) in Munich and Professor Karin Münzel of the Department of Neuropsychology has now investigated this discrepancy. More than 100 breast cancer patients from five hospitals and hemato-oncology praxes in Bavaria participated in the prospective, longitudinal study COGITO (short for “Cognitive Impairment in Therapy of Breast Cancer“).The researchers tested the hypothesis that confounding factors mask an underlying association between perceived cognitive dysfunction and actual cognitive compromise.  Among others, the effects of the possible confounders depression, negative affectivity (i.e., the disposition to experience negative emotional states like shame, guilt, or anger), and intensity of the chemotherapy on self-reports of cognitive functioning were considered..

But even when the effects of these factors were accounted for, there were no associations of self-reports with the results in any of twelve neuropsychological tests, and changes in test scores were not reflected in self-reports. Patients who reported cognitive dysfunction showed more depression and were more disposed to experience negative emotional states even before the start of therapy, but their test results did not differ from those of other patients. The intensity of chemotherapy also influenced subjective evaluations of cognitive functioning but did not affect the performance in cognitive tests.

Based on these findings, Dr. Hermelink concludes that depression, negative affectivity, and therapy burden contribute to pessimistic self-appraisals of cognitive functioning, irrespective of whether neuropsychological compromise is actually present or not. The subtle cancer-associated cognitive compromise detected by neuropsychological assessments, however, generally remains unnoticed by affected patients.

”Our findings imply that the cognitive compromise associated with cancer and cancer therapy that has been demonstrated in many studies is not what the patients complain about”, says Hermelink.

Dr. Hermelink emphasizes that although generally complaints of cognitive decline after chemotherapy are not based on actual compromise they still should be taken seriously. “Of course, there are exceptions to the general rule: subjective and objective deficits in cognitive function can coincide in individual patients. In any case, subjective perceptions of cognitive dysfunction represent a further burden for patients who are already under a great deal of pressure, and should therefore be addressed. However, it doesn’t help the patients to simplify the problem, to ignore the divergence of subjective and objective cognitive compromise, and to encourage the notion that complaints of ‘chemobrain’ usually are based on damage caused by chemotherapy. This attitude fosters expectations and fears and thus very likely even promotes subjective perceptions of cognitive dysfunction. “(CA/suwe)


”Two different sides of ‘chemobrain’: determinants and nondeterminants of self-perceived cognitive dysfunction in a prospective, randomized, multicenter study”;
Kerstin Hermelink, Helmut Küchenhoff, Michael Untch, Ingo Bauerfeind, Michael Patrick Lux, Markus Bühner, Juliane Manitz, Veronika Fensterer, Karin Münzel;
Psycho-Oncology online, 5 February 2010
DOI: 10.1002/pon.1695

Dr. Kerstin Hermelink
Medical Center of the University of Munich
Phone: +49 (0) 89 / 7095-7579
E-mail: kerstin.hermelink@med.uni-muenchen.de

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