Post-chemotherapy cognitive impairment
Encyclopedia
Post-chemotherapy cognitive impairment (PCCI) (also known as chemotherapy-induced cognitive dysfunction, chemo brain or chemo fog) describes the cognitive impairment that can result from chemotherapy
treatment. Approximately 20–30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The phenomenon first came to light because of the large number of breast cancer survivors who complained of changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy.
Although the causes and existence of post-chemotherapy cognitive impairment have been a subject of debate, recent studies have confirmed that post-chemotherapy cognitive impairment is a real, measurable side effect of chemotherapy that appears in some patients. While any cancer patient may experience temporary cognitive impairment due to stress, fatigue, and depression, the long-term symptoms of PCCI are almost exclusively seen in patients treated for breast cancer
, ovarian cancer
, prostate cancer
, and other cancers of the reproductive system.
PCCI is clinically important due to the large number of women who survive breast cancer, more aggressive dosing
of chemotherapeutic agents, and the use of chemotherapy as an adjuvant to other forms of treatment. In some patients, fear of PCCI can impact treatment decisions. The magnitude of chemotherapy-related cognitive changes and their impact on the activities of daily living
are uncertain.
, though the overall epidemiology
and prevalence
is not well known and may depend on many factors.
It generally affects about 10–40% of breast cancer patients, with higher rates among pre-menopausal women and patients who receive high-dose chemotherapy.
and semantic memory
, attention
and motor coordination
. These effects can impair a chemotherapy patient's ability to understand and make decisions regarding treatment, perform in school
or employment
and can reduce quality of life
. Survivors often report difficulty multitasking, comprehending what they've just read, following the thread of a conversation, and retrieving words
Breast cancer
survivors who were treated with chemotherapy have to work harder to perform tasks than survivors whose treatment was surgical. A year after treatment the brains of cancer survivors treated with chemotherapy had physically shrunk while those of people not treated with chemotherapy had not.
Post-chemotherapy cognitive impairment comes as a surprise to many cancer survivors. Often, survivors think their lives will return to normal when the cancer is gone, only to find that the lingering effects of post-chemotherapy cognitive impairment impede their efforts. Working, connecting with loved ones, carrying out day-to-day tasks—all can be very challenging for an impaired brain. Although post-chemotherapy cognitive impairment appears to be temporary, it can be quite long-lived, with some cases lasting 10 years or more.
PCCI is complex and factors other than the chemotherapeutic agents may impact cognitive functioning. Menopause
, the biological impact of a surgical procedure with anesthesia
, medication
s prescribed in addition to the chemotherapy, genetic predisposition
, hormone therapy
, emotional states (including anxiety
, depression
and fatigue), comorbid
conditions and paraneoplastic syndrome
may all co-occur and act as confounding
factors in the study or experience of PCCI.
Bortezomib
is known to cause reversible neuropathy to the sensory
and peripheral nervous system
s. In most cases there is no known way of reducing the effects of chemotherapeutic agents related to taxane
s, thalidomide
and platinum
-based compounds (oxaliplatin
is a notable exception to the latter category—though it does cause PCCI its effects can be buffered by infusion of calcium
and thought related to PCCI include the ability of the nerves to repair themselves, the ability of cells to excrete compounds, permeability of the blood-brain barrier
, damage done to DNA
including shortening of telomere
s and cellular oxidative stress
.
The importance of hormones, particularly estrogen, on cognitive function is underscored by the presence of cognitive impairment in breast cancer patients before chemotherapy is begun, the similarity of the cognitive impairments to several menopausal symptoms, the increased rate of PCCI in pre-menopausal women, and the fact that the symptoms can frequently be reversed by taking estrogen.
Other theories suggest vascular injury, inflammation
, autoimmunity
, anemia
and the presence of the epsilon 4 version of the apolipoprotein E
gene
.
Fifty-six of the 132 chemotherapy agents approved by the FDA have been reported to induce oxidative stress. The drug doxorubicin
(adriamycin) has been investigated as a PCCI-causing agent due to its production of reactive oxygen species
. It has been investigated in an animal model
with mice
.
Research has revealed that neural progenitor cells are particularly vulnerable to the cytotoxic effects of chemotherapy agents. 5-fluorouracil has been demonstrated to reduce the viability of neural progenitor cells by 55-70% at concentrations of 1 μM, whereas cancer cell lines exposed to 1 μM of 5-fluorouracil were unaffected. Other chemotherapy agents such as BCNU, cisplatin, and cytarabine also displayed toxicity to progenitor cells in vivo and in vitro. This is a concern because neural progenitor cells are the major dividing cell population in the brain, giving rise to neurons and glia.
Due to the critical role the hippocampus
plays in memory, it has been the focus of various studies involving post-chemotherapy cognitive impairment. The hippocampus is one of the rare areas of the brain that exhibits neurogenesis
. These new neurons created by the hippocampus are important for memory and learning and require a brain-derived neurotrophic factor
(BDNF) to form. 5-fluorouracil, a commonly used chemotherapy agent, has been shown to significantly reduce the levels of BDNF in the hippocampus of the rat. Methotextrate an agent widely used in the chemotherapy treatment of breast cancer, has also displayed a long-lasting dose dependent decrease in hippocampal cell proliferation in the rat following a single intravenous injection of the drug. This evidence suggests that chemotherapy agent toxicity to cells in the hippocampus may be partially responsible for the memory declines experienced by some patients.
Deficits in visuo-spatial, visual-motor, and visual memory functions are among the symptoms seen in post-chemotherapy patients. There is evidence that this may be due to damage to the visual system rather than caused by cognitive deficits. In one study 5-flouracil caused ocular toxicity in 25-38% of patients treated with the drug. Methotextrate also caused ocular toxicity in 25% of patients within 2–7 days of initial chemotherapy regimen with the drug. This evidence suggests that some of the visual based cognitive deficits experienced by cancer survivors may be due to damage at the ocular level rather than cognitive processing, but most likely it is due to a synergistic effect on both systems.
s, cognitive behavior therapy, erythropoietin
and stimulant drugs such as methylphenidate
, though as the mechanism of PCCI is not well understood the potential treatment options are equally theoretical.
Modafinil
, approved for narcolepsy
, has been used off-label in trials with people with symptoms of chemobrain. Modafinil is a wakefulness-promoting agent that can improve alertness and concentration and appears to be effective at least among women with breast cancer.
While taking estrogen will frequently reverse the symptoms when they appear in women with breast cancer, this carries health risks, including possibly promoting the proliferation of breast cancer cells.
, difficult to draw.
Several recent studies have advanced the field using neuroimaging
techniques. In 2005, Dr. Masatoshi Inagaki used magnetic resonance imaging
(MRI) to measure differences in brain volume between breast cancer patients exposed to chemotherapy and subjects unexposed. Subjects were tested at two periods. One year after surgery and again at three years post-surgery. Results from the first year study found smaller volumes of gray and white matter in patients exposed to chemotherapy. However, in the three year study, both exposed and unexposed breast cancer survivors were observed to have similar gray and white matter volumes. Altered brain structure in chemotherapy patients provides explanation for cognitive impairment.
Another study in 2007 investigated the differences in brain structure between two adult, monozygotic twin females. One underwent chemotherapy treatment for breast cancer, while the other did not have cancer and was not treated with chemotherapy. MRI scans were taken of both twins' brain while taking part in a working memory task. Results found that twin A (exposed to chemotherapy) experienced a broader spatial extent of activation in her brain than twin B (not exposed to chemotherapy). Twin A also reported a greater difficulty than twin B in completing the memory activity. The authors of this study declare that commonly chemotherapy patients will self-report cognitive complaints, although they perform within normal limits on neuropsychological tasks. MRI scans may provide evidence for this occurrence. Chemotherapy patients may require greater volume of neural circuitry to complete neuropsychological tasks compared to others.
Positron Emission Tomography
(PET) is also used to study post-chemotherapy cognitive impairment. In one study in 2007, scans were taken of patients exposed to adjuvant chemotherapy. Significantly altered blood flow in the brain was found, most notably in the frontal cortex and cerebellum. The most significant difference of blood flow was found in the inferior frontal gyrus. Authors report resting metabolism in this area is associated with performance on short term memory tasks.
survivor and support group
s as affecting a subset of individuals treated with chemotherapy
, who attributed it to the effects of the medication taken to treat their cancers.
The term chemobrain appears in publications at least as early as 1997.
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
treatment. Approximately 20–30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The phenomenon first came to light because of the large number of breast cancer survivors who complained of changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy.
Although the causes and existence of post-chemotherapy cognitive impairment have been a subject of debate, recent studies have confirmed that post-chemotherapy cognitive impairment is a real, measurable side effect of chemotherapy that appears in some patients. While any cancer patient may experience temporary cognitive impairment due to stress, fatigue, and depression, the long-term symptoms of PCCI are almost exclusively seen in patients treated for breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
, prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, and other cancers of the reproductive system.
PCCI is clinically important due to the large number of women who survive breast cancer, more aggressive dosing
Dose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
of chemotherapeutic agents, and the use of chemotherapy as an adjuvant to other forms of treatment. In some patients, fear of PCCI can impact treatment decisions. The magnitude of chemotherapy-related cognitive changes and their impact on the activities of daily living
Activities of daily living
Activities of Daily Living is a term used in healthcare to refer to daily self-care activities within an individual's place of residence, in outdoor environments, or both...
are uncertain.
Incidence
PCCI affects a subset of cancer survivorsCancer survivors
A cancer survivor is an individual with cancer of any type, current or past, who is still living. About 11 million Americans alive today—one in 30 people–are either currently undergoing treatment for cancer or have done so in the past." Currently nearly 65% of adults diagnosed with cancer in the...
, though the overall epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
and prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
is not well known and may depend on many factors.
It generally affects about 10–40% of breast cancer patients, with higher rates among pre-menopausal women and patients who receive high-dose chemotherapy.
Symptoms
The systems of the body most affected by chemotherapy drugs include visualVisual memory
Visual memory describes the relationship between perceptual processing and the encoding, storage and retrieval of the resulting neural representations. Visual memory occurs over a broad time range spanning from eye movements to years in order to visually navigate to a previously visited location...
and semantic memory
Semantic memory
Semantic memory refers to the memory of meanings, understandings, and other concept-based knowledge unrelated to specific experiences. The conscious recollection of factual information and general knowledge about the world is generally thought to be independent of context and personal relevance...
, attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
and motor coordination
Motor coordination
thumb|right|Motor coordination is shown in this animated sequence by [[Eadweard Muybridge]] of himself throwing a diskMotor coordination is the combination of body movements created with the kinematic and kinetic parameters that result in intended actions. Such movements usually smoothly and...
. These effects can impair a chemotherapy patient's ability to understand and make decisions regarding treatment, perform in school
School
A school is an institution designed for the teaching of students under the direction of teachers. Most countries have systems of formal education, which is commonly compulsory. In these systems, students progress through a series of schools...
or employment
Employment
Employment is a contract between two parties, one being the employer and the other being the employee. An employee may be defined as:- Employee :...
and can reduce quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
. Survivors often report difficulty multitasking, comprehending what they've just read, following the thread of a conversation, and retrieving words
Breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
survivors who were treated with chemotherapy have to work harder to perform tasks than survivors whose treatment was surgical. A year after treatment the brains of cancer survivors treated with chemotherapy had physically shrunk while those of people not treated with chemotherapy had not.
Post-chemotherapy cognitive impairment comes as a surprise to many cancer survivors. Often, survivors think their lives will return to normal when the cancer is gone, only to find that the lingering effects of post-chemotherapy cognitive impairment impede their efforts. Working, connecting with loved ones, carrying out day-to-day tasks—all can be very challenging for an impaired brain. Although post-chemotherapy cognitive impairment appears to be temporary, it can be quite long-lived, with some cases lasting 10 years or more.
Proposed mechanisms
The details of PCCI's causes and boundaries are not well known. Two major theories have been advanced: the direct effect of chemotherapy drugs on the brain, and the role of hormones in nervous system health.PCCI is complex and factors other than the chemotherapeutic agents may impact cognitive functioning. Menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
, the biological impact of a surgical procedure with anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
, medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s prescribed in addition to the chemotherapy, genetic predisposition
Genetic predisposition
A genetic predisposition is a genetic affectation which influences the phenotype of an individual organism within a species or population but by definition that phenotype can also be modified by the environmental conditions. In the rest of the population, conditions cannot have that effect...
, hormone therapy
Hormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
, emotional states (including anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
and fatigue), comorbid
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
conditions and paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
may all co-occur and act as confounding
Confounding
In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...
factors in the study or experience of PCCI.
Bortezomib
Bortezomib
Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma...
is known to cause reversible neuropathy to the sensory
Sensory system
A sensory system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory receptors, neural pathways, and parts of the brain involved in sensory perception. Commonly recognized sensory systems are those for vision, hearing, somatic...
and peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
s. In most cases there is no known way of reducing the effects of chemotherapeutic agents related to taxane
Taxane
The taxanes are diterpenes produced by the plants of the genus Taxus . As their name suggests, they were first derived from natural sources, but some have been synthesized artificially. Taxanes include paclitaxel and docetaxel . Paclitaxel was originally derived from the Pacific yew tree.Taxanes...
s, thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
and platinum
Platinum
Platinum is a chemical element with the chemical symbol Pt and an atomic number of 78. Its name is derived from the Spanish term platina del Pinto, which is literally translated into "little silver of the Pinto River." It is a dense, malleable, ductile, precious, gray-white transition metal...
-based compounds (oxaliplatin
Oxaliplatin
Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....
is a notable exception to the latter category—though it does cause PCCI its effects can be buffered by infusion of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and thought related to PCCI include the ability of the nerves to repair themselves, the ability of cells to excrete compounds, permeability of the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
, damage done to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
including shortening of telomere
Telomere
A telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos "end" and merοs "part"...
s and cellular oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
.
The importance of hormones, particularly estrogen, on cognitive function is underscored by the presence of cognitive impairment in breast cancer patients before chemotherapy is begun, the similarity of the cognitive impairments to several menopausal symptoms, the increased rate of PCCI in pre-menopausal women, and the fact that the symptoms can frequently be reversed by taking estrogen.
Other theories suggest vascular injury, inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and the presence of the epsilon 4 version of the apolipoprotein E
Apolipoprotein E
Apolipoprotein E is a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Fifty-six of the 132 chemotherapy agents approved by the FDA have been reported to induce oxidative stress. The drug doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
(adriamycin) has been investigated as a PCCI-causing agent due to its production of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
. It has been investigated in an animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
with mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
.
Research has revealed that neural progenitor cells are particularly vulnerable to the cytotoxic effects of chemotherapy agents. 5-fluorouracil has been demonstrated to reduce the viability of neural progenitor cells by 55-70% at concentrations of 1 μM, whereas cancer cell lines exposed to 1 μM of 5-fluorouracil were unaffected. Other chemotherapy agents such as BCNU, cisplatin, and cytarabine also displayed toxicity to progenitor cells in vivo and in vitro. This is a concern because neural progenitor cells are the major dividing cell population in the brain, giving rise to neurons and glia.
Due to the critical role the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
plays in memory, it has been the focus of various studies involving post-chemotherapy cognitive impairment. The hippocampus is one of the rare areas of the brain that exhibits neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
. These new neurons created by the hippocampus are important for memory and learning and require a brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...
(BDNF) to form. 5-fluorouracil, a commonly used chemotherapy agent, has been shown to significantly reduce the levels of BDNF in the hippocampus of the rat. Methotextrate an agent widely used in the chemotherapy treatment of breast cancer, has also displayed a long-lasting dose dependent decrease in hippocampal cell proliferation in the rat following a single intravenous injection of the drug. This evidence suggests that chemotherapy agent toxicity to cells in the hippocampus may be partially responsible for the memory declines experienced by some patients.
Deficits in visuo-spatial, visual-motor, and visual memory functions are among the symptoms seen in post-chemotherapy patients. There is evidence that this may be due to damage to the visual system rather than caused by cognitive deficits. In one study 5-flouracil caused ocular toxicity in 25-38% of patients treated with the drug. Methotextrate also caused ocular toxicity in 25% of patients within 2–7 days of initial chemotherapy regimen with the drug. This evidence suggests that some of the visual based cognitive deficits experienced by cancer survivors may be due to damage at the ocular level rather than cognitive processing, but most likely it is due to a synergistic effect on both systems.
Treatment
Hypothesized treatment options include the use of antioxidantAntioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, cognitive behavior therapy, erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
and stimulant drugs such as methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
, though as the mechanism of PCCI is not well understood the potential treatment options are equally theoretical.
Modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
, approved for narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, has been used off-label in trials with people with symptoms of chemobrain. Modafinil is a wakefulness-promoting agent that can improve alertness and concentration and appears to be effective at least among women with breast cancer.
While taking estrogen will frequently reverse the symptoms when they appear in women with breast cancer, this carries health risks, including possibly promoting the proliferation of breast cancer cells.
Research
Research on PCCI is limited, and studies on the subject have often been conflicting in results, in part due to differing means of assessing and defining the phenomenon, which makes comparison and synthesis difficult. Most studies have involved small samples, making generalization difficult, and there has been a focus on younger patients which makes conclusions about the largest group of cancer patients, the elderlyOld age
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...
, difficult to draw.
Several recent studies have advanced the field using neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
techniques. In 2005, Dr. Masatoshi Inagaki used magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) to measure differences in brain volume between breast cancer patients exposed to chemotherapy and subjects unexposed. Subjects were tested at two periods. One year after surgery and again at three years post-surgery. Results from the first year study found smaller volumes of gray and white matter in patients exposed to chemotherapy. However, in the three year study, both exposed and unexposed breast cancer survivors were observed to have similar gray and white matter volumes. Altered brain structure in chemotherapy patients provides explanation for cognitive impairment.
Another study in 2007 investigated the differences in brain structure between two adult, monozygotic twin females. One underwent chemotherapy treatment for breast cancer, while the other did not have cancer and was not treated with chemotherapy. MRI scans were taken of both twins' brain while taking part in a working memory task. Results found that twin A (exposed to chemotherapy) experienced a broader spatial extent of activation in her brain than twin B (not exposed to chemotherapy). Twin A also reported a greater difficulty than twin B in completing the memory activity. The authors of this study declare that commonly chemotherapy patients will self-report cognitive complaints, although they perform within normal limits on neuropsychological tasks. MRI scans may provide evidence for this occurrence. Chemotherapy patients may require greater volume of neural circuitry to complete neuropsychological tasks compared to others.
Positron Emission Tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) is also used to study post-chemotherapy cognitive impairment. In one study in 2007, scans were taken of patients exposed to adjuvant chemotherapy. Significantly altered blood flow in the brain was found, most notably in the frontal cortex and cerebellum. The most significant difference of blood flow was found in the inferior frontal gyrus. Authors report resting metabolism in this area is associated with performance on short term memory tasks.
Prognosis
The ultimate outcome is variable, with symptoms in some patients disappearing within 4 years, yet others were noted to have symptoms lasting almost 10 years after treatment.History
The symptoms of PCCI were recognized by researchers in the 1980s, who typically described it as mild cognitive impairment subsequent to successful cancer treatment. Some authors say that it was identified primarily in breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
survivor and support group
Support group
In a support group, members provide each other with various types of help, usually nonprofessional and nonmaterial, for a particular shared, usually burdensome, characteristic...
s as affecting a subset of individuals treated with chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, who attributed it to the effects of the medication taken to treat their cancers.
The term chemobrain appears in publications at least as early as 1997.
External links
- American Cancer Society - Chemobrain
- Column from Jane BrodyJane BrodyJane Ellen Brody is an American author on science and nutrition topics, who has written a number of books and reported extensively for The New York Times as its "Personal Health" columnist, which appears weekly in the paper's Science Times section, which has been syndicated nationwide...
at The New York Times