Impairment in cognitive functioning, including decreased attention span and impaired perception and thinking, is commonly associated with fatigue.[47,48] Although fatigue and cognitive impairments are linked, the mechanism underlying this association is unclear. Mental demands inherent in the diagnosis and treatment of cancer have been well documented, but little is known about the concomitant problem of attention fatigue in people with cancer. Attention problems are common during and after cancer treatment. Some of the reported attention problems may be caused by the fatigue of directed attention.[49,50] Attention fatigue may be relieved by activities that promote rest and recovery of directed attention. Although sleep is necessary for relieving attention fatigue and restoring attention, it is insufficient when attention demands are high. Empirical literature suggests that the natural environment contains the properties for restoring directed attention and relieving attention fatigue.
Sleep Disorders and Inactivity
Disrupted sleep, poor sleep hygiene, decreased nighttime sleep or excessive daytime sleep, and inactivity may be causative or contributing factors in CRF. Patients with less daytime activity and more nighttime awakenings were noted to consistently report higher levels of CRF. Those with lower peak-activity scores, as measured by wristwatch activity monitors, experienced higher levels of fatigue.
Sleep disorders clearly contribute to fatigue  and may differentially affect fatigue ratings, depending on the time of the rating. A study evaluating fatigue in women undergoing radiation therapy for breast cancer found that sleep had a greater influence on morning fatigue values than on evening fatigue scores. In a similar study of men undergoing radiation therapy for prostate cancer, sleep contributed to both morning and evening fatigue levels. However, fatigue and sleep can also be distinct problems. One study that resulted in significant improvement in sleep with the use of cognitive behavioral therapy did not significantly affect fatigue.
Medications other than chemotherapy may contribute to fatigue. Opioids used in the treatment of cancer-related pain are often associated with sedation, though the degree of sedation varies among individuals. Opioids are known to alter the normal function of the hypothalamic secretion of gonadotropin-releasing hormone. Hypogonadism may be found in patients with advanced cancer and can contribute to fatigue during cancer treatment. One case-control study examined the effects of chronic oral opioid administration in survivors of cancer and, consistent with the research on intrathecal administration, found marked central hypogonadism among the opioid users with significant symptoms of sexual dysfunction, depression, and fatigue. One ongoing trial (NCT00965341) is studying whether and how testosterone replacement therapy might affect fatigue in men with advanced cancer and low testosterone levels.
Other medications-including tricyclic antidepressants, neuroleptics, beta blockers, benzodiazepines, and antihistamines-may produce side effects of sedation. In addition, concurrent medications such as analgesics, hypnotics, antidepressants, antiemetics, steroids, or anticonvulsants-many of which act on the central nervous system-can significantly compound the problem of fatigue. The coadministration of multiple drugs with varying side effects may compound fatigue symptoms.
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