Innovations In Clinical Neuroscience

JAN-FEB 2018

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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R E V I E W 41 ICNS Innovations in Clinical Neuroscience • January–February 2018 • Volume 15 • Number 1–2 that has been used to assess the major cognitive domains identified as key for cancer-related treatments. 24,96–98 The standard CDR cognitive assessment battery includes immediate and delayed word recall, word recognition, picture recognition, simple reaction time, digit vigilance, choice reaction time, numeric working memory, and spatial working memory. Additional individual tests, such as executive function, can be added to the standard battery to target specific cognitive domains. The CDR demonstrated sensitivity in detecting cancer treatment-related cognitive changes in a clinical trial of patients with advanced colorectal cancer by revealing that patients treated with recombinant IL-2 (rIL-2) with chemotherapy experienced significant cognitive impairments, especially in reaction time, picture recognition, and vigilance compared to patients treated only with chemotherapy. Additionally, baseline cognitive functioning was restored within 10 days following the cessation of rIL-2. 96 In one study of adult patients with cancer (Hodgkin's disease, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, or multiple myeloma), the CDR found marked impairments on the Power of Attention domain (focused attention, information processing ability, and ability to concentrate), as well as slowing in speed of retrieval of information. 98 In studies of patients with breast cancer, the CDR system has recorded significant impairment in attention, verbal memory, visual recognition memory, and working memory. 24,78 CNS Vital Signs is another a computerized neurocognitive test battery that has been validated in a broad age range and across both clinical and nonclinical populations, including cancer patients. 99 The CNS Vital Signs platform has 10 normed neurocognitive tests available, including verbal memory, visual memory, finger tapping, symbol digit coding, the Stroop test, shifting attention, continuous performance test, perception of emotions, nonverbal reasoning, and four-part continuous performance test. The 10 normed neurocognitive tests of CNS Vital Signs can be arranged into a custom testing panel for standardized data collection and can be complemented with additional 26 un- normed cognitive tests. In one prospective study examining the incidence and severity of cognitive dysfunction in meningioma patients before and after surgery, cognitive assessment using the CNS Vital Signs battery found that meningioma patients demonstrated significantly lower scores in all cognitive domains (i.e., memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, processing speed, and executive functioning) pre- and post- operatively compared to normative data, which is consistent with previous research examining cognitive functioning in meningioma patients with conventional paper-and-pencil cognitive measures. 100 Additional analyses revealed that patients demonstrated improvement in test performance post-operatively in all domains, with the exception of psychomotor speed and reaction time. Evaluation of cognitive functioning using the CNS Vital Signs battery in lymphoma survivors who had completed treatment in the past five years revealed that lymphoma survivors obtained significantly poorer scores on measures of attention and executive functioning compared to controls. 32 CogState is another computerized testing platform that offers a series of valid and reliable computerized neurocognitive tests that can be customized for cognitive assessment of cancer patients. The CogState Brief Battery assesses four core cognitive domains: processing speed, attention, visual learning, and working memory, and has been used extensively in evaluating cognitive functioning and impairments in a range of clinical indications in adult and pediatric populations. A recent study utilized the CogState Brief Battery Tests and conceptually matched traditional neuropsychological tests and a self-report measure of daily functioning (the Functional Activities Questionnaire) in 53 post- menopausal women (26 breast cancer survivors and 27 healthy controls). 101 Analyses revealed significant correlations between the CogState Brief Battery tests on some, but not all, traditional neuropsychological tests. 101 These researchers reported preliminary support for criterion validity but noted additional research was needed to further confirm the use of CogState tests to detect subtle cognitive differences between breast cancer survivors and healthy controls, given the small sample size and low base rate of cognitive impairment in the study. In a separate, ongoing study collecting cerebrospinal fluid while prospectively assessing cognitive functioning in patients with acute lymphoblastic leukemia (ALL) during and after chemotherapy, baseline data found that 85 percent of patients demonstrated intact cognitive functioning in domains of working memory, executive functioning, learning, processing speed, and attention on the CogState computerized battery compared to same age peers along with the baseline cerebral spinal fluid (CSF) markers being within expected normal ranges. 102 MANAGEMENT AND TREATMENT INTERVENTIONS FOR COGNITIVE CHANGES IN CANCER Some interventions might be useful to manage the cognitive changes experienced by patients with cancer. Possible nonpharmacological interventions include cognitive rehabilitation, occupational therapy, instruction in coping strategies, behavioral modification, and mindfulness practices to manage distress, pain, sleep disturbances, and fatigue. 5,103 Clinically it is usually appropriate to begin with nonpharmacologic interventions. For instance, attention retraining and instructional use of compensatory strategies have shown some promise in addressing cognitive complaints and mental fatigue in patients with cancer. 104 Similarly, cognitive rehabilitation and training techniques that employed repeated skills training, awareness practice, and adaptive difficulty levels showed positive benefits in cognitive organization and self-reported quality of life. 105 A multidisciplinary approach delivered by a team of psychologists, speech and language pathologists, and occupational and vocational specialists has been shown to facilitate improved community independence and employment outcomes in a study of patients diagnosed with brain tumors. 106 Some of the neurotoxic fatigue and cognitive side effects of cancer chemotherapy might be managed with psychostimulant medications. 8 It is important to note that psychostimulants are generally prescribed for a limited period of time during chemotherapy and that the long-term benefits, if any, for cognition in survivors of cancer has not been assessed. Gehring et al 107 found that patients with brain tumors treated with methylphenidate or modafinil had improvements in divided attention, particularly in patients who had the greatest cognitive impairment at baseline. Using the CDR computerized test system, Kohli et al 97 found that modafinil 200mg given daily for eight weeks improved cognitive functioning in the domains of memory and attention in survivors of breast cancer, specifically the speed of memory and quality of episodic memory. Donepezil also has been used to treat cancer-related fatigue, attention, and memory,

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