Oncology reviews
Cognitive impairment and chemotherapy: a brief overview

https://doi.org/10.1016/j.critrevonc.2017.08.001Get rights and content

Highlights

  • Chemotherapy has significantly increased overall survival in cancer patients.

  • Chemotherapeutic drugs cause various side effects.

  • An emerging side effect is the decline in cognitive function.

  • Cognitive impairment has a serious impact on quality of life (QoL).

Abstract

Patients with cancer are experiencing long-term survival following chemotherapy, but the treatment may also be associated with short and long-term toxicity, including the possibility of cognitive dysfunction. A literature overview indicated a significant association between chemotherapy and cognitive impairment but prospective longitudinal research is warranted to examine the degree and persisting nature of this decline. Although chemotherapeutic agents are unlikely to cross the blood-brain barrier, it has been alleged that the occurrence of neurotoxicity is linked to the pro-inflammatory cytokine pathways. Moreover in most cases many other factors could play an ancillary and concomitant role. The contribution of hormone therapy as well as emotional, social, behavioural and genetic factors should always be considered.

Especially physical activity and cognitive training appear promising in the management of cognitive impairment but additional studies are required to establish their efficacy.

Introduction

In the last years chemotherapy has significantly increased overall survival in patients with different cancer types. However, chemotherapy drugs often cause various side effects and many patients report a decline in cognitive function. These disordersaffect several cognitive domains over time: memory, speed of cognitive processes and executive functions are especially involved (Tchen et al., 2003, Conroy et al., 2013a, Koppelmans et al., 2012, Zimmer et al., 2015, Wefel et al., 2010, Hess et al., 2015, Hermelink et al., 2010, Tager et al., 2010, Deprez et al., 2012, Ahles et al., 2010, Jim et al., 2012, Hutchinson et al., 2012, Amidi et al., 2015, Iconomou et al., 2004, Ono et al., 2015, Cruzado et al., 2014, Wefel et al., 2014). A variety of other factors, different to chemotherapy may contribute to cognitive impairment in cancer patients (Table 1) (Cimprich et al., 2005, Jung and Cimprich, 2014, Kugaya et al., 2000, Shelby et al., 2008, Young et al., 2017, Koleck et al., 2014, Hermelink et al., 2017, Rieben et al., 2016, Jung and Visovatti, 2017, Le Rhun et al., 2015, Wu and Amidi, 2017, McGinty et al., 2014, Merritt et al., 2017, Miskowiak et al., 2017, Matsuzaka et al., 2017, Collins and Williams-Gray, 2016). Moreover, cognitive function decline always has a serious impact on the quality of life (QoL), especially in long-term survivors (Amidi et al., 2015, Iconomou et al., 2004, Ono et al., 2015). In literature these dysfunctions are mainly reported in breast cancer (Tchen et al., 2003, Conroy et al., 2013a, Koppelmans et al., 2012, Wefel et al., 2010, Tager et al., 2010, Ahles et al., 2010, Jim et al., 2012, Ono et al., 2015) trials, but many other types of cancer can be involved (Zimmer et al., 2015, Hess et al., 2015, Amidi et al., 2015, Iconomou et al., 2004).

In this brief non systematic review we discuss these emerging problems, with some insights into their etiology and a focus into some aspects of their diagnosis and management.

Section snippets

Chemotherapy and cognitive disorders

There is strong evidence that chemotherapy in cancer patients can cause a decline in short-term cognitive ability (Koppelmans et al., 2012, Wefel et al., 2010). By contrast, data about long-term chemotherapy effects are unclear (Koppelmans et al., 2012, Amidi et al., 2015). Several studies compared cancer patients treated with chemotherapy with healthy subjects and showed that chemotherapy can lead to cognitive function deterioration (Tchen et al., 2003, Conroy et al., 2013a, Koppelmans et al.,

Cognitive impairment detections

A very important issue in the diagnostic process and management of cognitive disorders is the presence of a high number of different neuro-cognitive tests (Supplementary Table 2) (Faust and Fogel, 1989, Fogel, 1991, Folstein et al., 1975, Conners and Barta, 1967, Rey, 1964, Brown et al., 2007, Wechsler, 1981, Wechsler, 1987, Wilkinson and Robertson, 2006, Anon., 1999, Delis et al., 2001, Levine et al., 2004, Benedict et al., 1998, Ruff et al., 1996, Erlanger et al., 2002, ISPOCD, 2006, EBCTCG,

Cognitive impairment etiology in cancer patients

Many preclinical studies suggest the hypothesis that systemic inflammatory processes contribute to the cognitive disorders genesis in cancer patients (Dantzer et al., 2008, Haroon et al., 2012, Miller et al., 2008, Irwin and Cole, 2011, Wang et al., 2015, Yang et al., 2014, Reichenberg et al., 2001, Spath-Schwalbe et al., 1998). In these patients the immune cells continuous activation produce pro-inflammatory cytokines which interact with multiple CNS pathways involved in the development of

Non pharmacological management: exercise effects

An increase in physical activity is associated with a cognitive function improvement in animal and human studies (Zimmer et al., 2016). The helpful effect of yoga, Qigong and Tai Chi has been evaluated in some studies in women with cognitive function deterioration after breast cancer treatment (Reid-Arndt et al., 2012, Oh et al., 2012, Culos-Reed et al., 2006, Janelsins et al., 2012). In the study by Janelsins et al., 358 patients (75% breast cancer patients) were randomized to standard care or

Conclusions

Cognitive impairments during and after chemotherapy in cancer patients is undoubtedly a very relevant emerging issue. Cancer patients are experiencing long-term survival after chemotherapy but these treatments can be related with long-term toxicity, including cognitive impairment. The literature data showed a significant link between chemotherapy and cognitive disturbances but the degree and nature of this decline is not clear. Chemotherapeutic drugs are not able to cross the blood-brain

Conflict of interest statement

The authors have no financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work.

Authors contribute

All authors of this manuscript have directly participated in its planning and execution.

Funding statement

None.

Acknowledgement

The authors want to thank Peter Head and Camilla Amati for their valuable support in medical writing assistance.

Milena Vitali MD Since 2001 she has been working at National Cancer Institute of Milan, Italy. She is currently dedicated to the research and treatment of Thoracic Tumors. She is also committed in the follow-up planning of patients and in the oncologic therapy side effects management. She has actively participated as co-investigator in numerous clinical trials in “Good Clinical Practice” carried out at National Cancer Institute of Milan over the last ten years. She is involved as clinician as

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    Milena Vitali MD Since 2001 she has been working at National Cancer Institute of Milan, Italy. She is currently dedicated to the research and treatment of Thoracic Tumors. She is also committed in the follow-up planning of patients and in the oncologic therapy side effects management. She has actively participated as co-investigator in numerous clinical trials in “Good Clinical Practice” carried out at National Cancer Institute of Milan over the last ten years. She is involved as clinician as well as co-investigator research projects in the field of oncologic simultaneous palliative care. She has co-authored about 20 peer-reviewed publications regarding clinical oncology.

    Carla Ida Ripamonti MD specialized in medical oncology and clinical pharmacology, Head of Supportive Care in Cancer Unit at National Cancer Institute of Milan Italy, Lifetime Board Advisers of IAHPC; ESMO Faculty Member Educational Committee Supportive and Palliative Care; Member of Directors of the ESMO Palliative Care Working Group (PCWG), Member of Directors of the MASCC, Vice Director of Italian Network of Supportive Care in Cancer (NICSO) .Graduated in Medicine and Surgery at the University of Milan in 1983 (110/110 cun laudem). As a post-graduate she specialized in Oncology (1987) and in Clinical Pharmacology (1991). Trained in the Michael Sobell House Hospice, Northwood, London; the Continuing Care Unit c/o The Royal Marsden Hospital, London; the Palliative Care Unit, Edmonton General Hospital, Alberta University, Canada, Palliative Care Division of the MD Anderson Cancer Center, University of Texas, Houston. Working from 1983 till December 2008 at the Pain Therapy and Palliative Care Division of the National Cancer Institute of Milan concerning three activities: clinical, research and continuing medical and nursing education as Assistant of Director and then as Vice Director. From January 2009 Head of the Supportive Care in Cancer Unit of the IRCCS Foundation National Cancer Institute of Milan, Italy. Consultant of the Collaborative Centre for Cancer Pain Relief of the W.H.O. Writer of ESMO Guidelines and for AIOM guidelines on Bone metastases. Author/Co-author of more than 300 papers published in international Journal as well as author of instruction manuals for doctors, nurses, volunteers regarding Palliative Medicine. Author/co-author of more than 130 chapters of books. Adjunct Professor in the Department of Oncology, Division of Palliative Care Medicine c/o Cross Cancer Institute, University of Alberta, Canada; Professor of Pain Therapy, Palliative Medicine and Supportive Care at the School of Specialization in Oncology of the University of Milan, and European teacher of Palliative Medicine for ESMO (European Society Medical Oncology).

    Filippo de Braud, MD, is currently Director of Medical Oncology Department and Division of the National Cancer Institute, Milan, where his principal area of expertise is clinical research in oncology. In 1984, Dr de Braud received his medical degree in medicine from the University of Milan and continued his training in oncology at various institutions, including the Royal Free Hospital School of Medicine, London, UK, the Wayne State University, Detroit, MI, USA, and the Institute Gustave Roussy, Paris, FR. He has held clinical posts at the European Institute of Oncology, where he was appointed Deputy Director of the Medical Oncology Division in 1994, later becoming Director of Division of Clinical Pharmacology and New Drugs Development since August 2011 when he was appointed as Chief of Division of Medical Oncology at National Cancer Institute, Milan. He is leading researchers in new drugs development (Phase I and early Phase II studies) and teaching in academic environment at University of Milan (Full professor), Rome and Ferrara. Since 2000, he has been appointed Scientific Advisor and Member of Committee at Italian Medicine Agency AIFA, Ministry of Health, and several Pharmaceutical Companies. Dr de Braud is the author or coauthor of over 270 publications in medical oncology

    Marina Chiara Garassino, MD, is the Head of the thoracic oncology Unit of the National Cancer Institute of Milan, where her principle area of research is thoracic malignancies (lung cancer, mesothelioma, thymic malignancies). Her most important work was the TAILOR trial. She is principal investigator of several international and national trials. She is the PI of several independent trials funded within Program In 1995, Dr Garassino received her medical degree in medicine from the University of Milan, in 1999 she achieved her board specialization in Oncology and continued her training in oncology at various European institutions. She has held clinical post at the Fatebenefratelli e Oftalmico Hospital. She is author and co-author of several papers on lung cancer and she is in the steering commitee of italian and international trials. She is the ESMO National Representative and she has been the Chair of the Young Italian National Society (2001-2006), she is a member of the ESMO Lung Cancer Faculty and EMA expert for Lung Cancer.

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