Cognitive effects of cancer and chemotherapy

DEFINITION: Cancerous brain tumors often lead to neurological problems such as difficulties with memory, attention span, speed of mental processing, and reasoning skills. Chemotherapy for all types of cancer can also cause deficits in normal, healthy cognitive functioning. The drugs used can interfere with mental processing and produce what some refer to as “chemobrain” or “chemofog,” but the problems typically subside shortly after the treatment is terminated. However, for some individuals, the difficulties will remain for months or even years after chemotherapy has ended.

Diagnosing cognitive deficits: Cognitive functioning refers to a host of processes that are performed by the brain that allow people to adapt to their environment and make informed judgments. Cognitive skills refer to the ability to attend to and concentrate on one or more tasks at the same time, to initiate and plan future actions, to engage in verbal or written language, and to have the ability to learn and recall information. All of these skills help people cope in a complex world. When one or more of these processes are short-circuited, mild or even devastating consequences can ensue.

People with cognitive problems are likely to find it difficult to return to work or school and to function as well as they did in the past. In more severe cases, people might find it difficult to fully manage their normal daily activities. Their ability to maintain social relationships, to manage a household, and to monitor their own self-care during treatment can be significantly diminished.

Because healthy cognitive functioning is so important, any dysfunction regarding cognitive processes brought on by cancer directly or due to chemotherapy must be diagnosed, assessed, and closely monitored. The preponderance of evidence reveals that chemotherapy in standard-dose ranges can bring on cognitive impairments during treatment periods in approximately 75 percent of cancer patients. Furthermore, 35 percent of patients experience cognitive issues for several months. If high-dose treatments are used, research has shown that there is a significantly greater likelihood that normal functioning will be adversely affected. Neuropsychological testing with instruments such as the Halstead-Reitan Neuropsychological Battery, the Mini-Mental Status Exam, and the Weschler Adult Intelligence Scale is commonly done to diagnose and assess cognitive problems. These tests are crucial not only for providing an initial benchmark regarding how well an individual is functioning but also for long-term tracking of cognitive performance during and after cancer treatment.

Behavioral symptoms: Patients undergoing chemotherapy often report that their ability to think is clouded and that they feel as if their heads are in a fog. Their ability to think and process information efficiently seems slowed and compromised. Neurological and neuropsychological testing reveals that some chemotherapy patients will have difficulty concentrating or paying attention. For others, the primary cognitive deficits emerge in terms of memory processing. Although long-term memory appears to be spared, short-term memory, including the manipulation of concepts that are present in the immediate consciousness, can be severely affected. Problems with comprehension, combined with language difficulties, can make it very difficult for a person to engage in multitasking, an ability that is very important for adequate functioning in the workplace or in school.

Almost any combination of cognitive symptoms can result in problems with decision-making and reasoning. Fortunately, the cognitive symptoms experienced by most cancer patients are usually mild to moderate. Although the literature contains reports of severe cases of delirium (mental confusion) due in part to chemotherapy, these instances are rare. In addition, in the vast majority of people with deficits brought on by cancer-fighting drugs, particularly adults, the chemo-induced cognitive problems are usually transient.

Young children undergoing chemotherapy are more susceptible to long-term cognitive deficits. This is most likely because their central nervous systems are still immature, and the drugs are affecting the development of critical brain structures that are involved in mental processing. Long-term consequences for young children include an increased risk for developing a learning disability or attention-deficit disability, a general lowering of the intelligence quotient, and overall lowering of academic success in school.

Possible causes and mechanisms involved: Although numerous studies have been conducted on the effects of chemotherapy agents on cognitive functioning, relatively little is known about the specific mechanisms that create the deficits. It is known that most chemotherapy drugs do not easily cross the blood-brain barrier. This protective barrier controls the types of substances that can leave the blood supply and enter the central nervous system. Because most chemotherapy drugs have difficulty crossing the barrier, they appear to exert their effect on the brain by influencing multiple secondary mechanisms that ultimately produce cognitive impairments.

Several chemotherapy agents have been implicated in a neurological impairment called leukoencephalopathy, which is characterized by profound changes in the brain’s white matter. This condition could be caused by drugs coming into contact with the brain’s glial cells, which form the protective myelin sheath that covers some neurons. If the drugs are toxic to the glial cells, resulting in cell death, this could lead to abnormal neural signaling and ultimately influence cognitive processing. Another possible mechanism could be chemotherapy-induced anemia, which has long been associated with poor mental functioning, as is the case with vascular dementia. When the brain is not getting enough oxygen, it can result in deficiencies in alertness, attention, concentration, and memory.

Brain tumors can lead to deleterious effects on cognition through several mechanisms. First, as brain tumors begin to grow, they can displace healthy structures adjacent to the cancer and alter the functional properties of neurons. Typically, as the tumor grows, more and more healthy tissue will be displaced, leading to more cognitive deficits. One explanation for the problems that develop is that the tumor growth squeezes adjacent structures to the point that the brain tissue that makes up the structure is no longer able to function normally. If this squeezing occurs over a long period of time, it could result in massive cell destruction, leading to permanent cognitive impairment.

Management and treatment: Usually, chemotherapy-induced cognitive deficits begin to subside shortly after treatment has ended. If the deficits do not go away, there are ways to manage the impairments. Neurocognitive-enhancing drugs can be prescribed to help counteract whatever mechanisms might be involved in maintaining the cognitive deficiencies. Behavioral stimulants, such as methylphenidate, commonly used in children with attention-deficient disorder, have been found to increase alertness, concentration, and energy levels in adults who have suffered from cognitive problems brought on by chemotherapy. Researchers have also found similarities between cytokines of patients with depression and those with cognitive impairments from chemotherapy. Thus, targeting those cytokines with antidepressant drugs has proven beneficial for patients dealing with cognitive side effects of chemotherapy.

Another treatment alternative involves cognitive rehabilitation therapy. This form of therapy targets specific areas of need, such as multitasking, organizational skills, or short-term memory, and teaches patients to practice mental exercises that force them to use their brains in a way that strengthens these areas. In some instances, patients are able to develop new coping strategies that compensate for cognitive processes that have become compromised.

Bibliography

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