Cancer-related cognitive impairment (CRCI) is not limited to chemotherapy. A multidisciplinary approach has improved knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life (QoL) during and after cancer. Those are conclusions from a review of literature published between 2012 and 2019 and conducted by Prof. Florence Joly of the Medical Oncology Department, Centre François Baclesse in Caen, France and colleagues. The findings are published on 16 October 2019 in the Annals of Oncology.
The authors wrote that in patients with non-central nervous system (CNS) cancers, CRCI is mainly studied after chemotherapy. The relation between objective and subjective cognitive problems is still debated with complaints often beeing linked to psychological factors. State-of-the-art published in 2011 and 2015 by the International Cancer and Cognition Task Force, primarily focussed on neuropsychological tests and clinical data with chemotherapy. Since then, a growing body of literature has highlighted the potential effects of other cancer treatments and pathophysiological mechanisms. New generations of hormone therapies, targeted therapies, and immunotherapy have resulted in improved survival rates for some patients with potential impact on cognition. Consequently, the long-term toxic impact of treatment on neurological function is an important issue in terms of QoL.
The study team wrote in the study background that it remains uncertain whether cognitive deficits result from the treatment, the cancer itself, and/or psychological factors. Moreover, studies have suggested that factors such as age, genetic polymorphisms, and psychosocial components may predispose to a higher risk of cognitive impairment. As cognitive difficulties have a negative impact on QoL in terms of autonomy, return to work, social relationships, and self-confidence in the context of long-term cancer care, there is a growing demand from patients for CRCI management. This has led to studies implementing cognitive rehabilitation in cancer patients.
In their article, the authors present an update on CRCI in non-CNS cancers, taking into consideration the increasing use of newer anticancer therapies and the development of multidisciplinary (pre-clinical, imaging) and interventional (management) research strategies. In that context, the authors performed PubMed search in terms of articles published between 2012 and March 2019 by using as keywords ‘cognition’, ‘cancer’, ‘antineoplastic agents’ or ‘chemotherapy’.
Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. The study team found that recent investigations show that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits.
Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy.
In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response.
An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens.
Multidisciplinary cooperation between oncologists, neurologists, imaging researchers, and neuroscientists is encouraged to define mechanisms of CRCI and to optimise medical care and patients’ rehabilitation. Early detection of cognitive impairment is needed, especially in elderly patients who could be referred to an onco-geriatrician and/or neurologist to screen for cognitive impairment before and during treatment. Management of CRCI should be incorporated into clinical practice as for patients with neurodegenerative disease.
The Cancer and Cognition Platform is supported by the French Ligue contre le Cancer.
Reference
Lange M, Joly F, Vardy J, et al. Cancer-related cognitive impairment: an update onstate of the art, detection, and management strategies in cancer survivors. Annals of Oncology; Published online 16 October 2019. pii: mdz410. doi: 10.1093/annonc/mdz410.