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Cognitive Dysfunction Cancer, Chemotherapy and Cognitive Dysfunction Jörg Dietrich 1 and Jochen Kaiser 2 1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, US; 2. Institute of Medical Psychology, Medical Faculty, Goethe University, Frankfurt, Germany Abstract Decline in cognitive function, such as memory impairment, is one of the most commonly reported symptoms in cancer patients. Importantly, cognitive impairment is not restricted to patients treated for brain tumors, but also frequently present in patients treated for tumors outside the nervous system. Recent discoveries from preclinical and translational studies have defined various risk factors and mechanisms underlying such symptoms. The translation of these findings into clinical practice will improve patient management by limiting the degree of neurotoxicity from current therapies, and by exploring novel mechanisms of brain repair. Keywords Cognitive function, memory impairment, cancer, chemotherapy, radiation, neural progenitor cells Disclosure: Jörg Dietrich received support from the National Institute of Health, the American Academy of Neurology Foundation, and the American Cancer Society. Jörg Dietrich also received generous philanthropic support from the family foundations of Sheila McPhee, Ronald Tawil and Bryan Lockwood. Jochen Kaiser has nothing to declare in relation to this article. No funding was received for the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: January 12, 2016 Accepted: February 11, 2016 Citation: US Neurology, 2016;12(1):43–5 Correspondence: Jörg Dietrich, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Yawkey 9E, Boston, MA 02114, USA E: Dietrich.Jorg@mgh.harvard.edu Neurocognitive function is commonly compromised in cancer patients. While symptoms can be caused by the tumor itself and are commonly seen in patients with brain tumors, the etiology of neurocognitive deficits is much more complex in patients treated for tumors outside the nervous system. Impaired cognition can be present in cancer patients prior to treatment; however, treatment related adverse effects from c hemotherapy and radiation are well known to cause harmful effects on the brain and play a significant role in the development and progression of neurocognitive symptoms. 1 In addition, various co-morbidities, mood and sleeping disorders, and medication effects can affect neurocognitive function (see Figure 1). It therefore can be difficult to delineate the exact contribution of each of these factors in clinical practice, posing a significant challenge to patient management. As disruption in neurocognitive function can be a major cause of impaired quality of life, attention to these symptoms and consideration of possible therapeutic interventions directed to improve neurocognitive deficits have become increasingly important in clinical oncology and cancer survivorship. Chemotherapy Effects on Neurocognitive Function The most frequently described neurocognitive problems in patients treated with various chemotherapy regimens include memory and TOU CH MED ICA L MEDIA learning deficits, alterations of attention, concentration, processing speed and executive function. 2 Symptoms can be of delayed onset and progressive for years after cessation of tumor therapy. While neurocognitive adverse effects from chemotherapy have long been recognized in long-term survivors of childhood cancer, 3,4 adult cancer patients can be equally affected, and chemotherapy associated cognitive dysfunction appears to be more common than previously anticipated. 1,5-8 Cognitive dysfunction has been reported in 15–95% of patients treated with chemotherapy, 5,6,9 depending on study design, patient population and the battery of neuropsychological tests administered. While cognitive impairment has been confirmed in patients treated for various cancer types, 10–12 most compelling studies were done in breast cancer patients, of whom 20–40% show cognitive deficits on post-treatment evaluation. 6,8,13–18 Symptoms might be of delayed onset and follow a progressive pattern. Approximately 30–60% of breast cancer survivors demonstrate cognitive deficits even up to 20 years after active cancer therapy. 18–20 Experimental studies have revealed insights into the underlying mechanisms of cognitive dysfunction in cancer patients. Specifically, a large number of animal studies have discovered the cell-biological effects of various chemotherapeutic drugs on the central nervous system. 21 Neurocognitive adverse effects have been observed with all categories of chemotherapeutic 43