Theorizes that chemotherapy has cumulative deleterious effects on CNS cells or vasculature.
Process has now been renamed as cancer-related cognitive impairment.
Impairment of cognitive function is usually subtle and may be intermittent.
As many as 75% of cancer patients experience cognitive impairment during or after treatment for cancer.
In up to 35% of patients who experience cognitive impairment, it may persist for months or years following treatment.
Cancer related cognitive impairment can process for years after treatment completion.
Breast cancer has been the most studied tumor type with cancer related cognitive impairment.
Evidence for cancer related cognitive impairment has been demonstrated in other cancers besides breast cancer, including lymphoma, head and neck cancers, brain tumors, and in patients who have received stem cell transplants.
Surveys suggest approximately 77% of patients with a history of breast cancer who receive chemotherapy with or without endocrine therapy and 45% who receive only endocrine therapy report cognitive symptoms during or soon after treatment.
More than 5 million Americans could be living with long-lasting cognitive difficulties from cancer and its treatments.
Despite complaints of memory and attention complaints cancer survivors frequently perform in the normal range on neuropsychological evaluations by recruiting additional areas of the brain to perform tasks.
Breast cancer chemotherapy is often associated with persistent cognitive problems that can reduce quality of life.
Cancer therapies, such as chemotherapy and cranial radiation, promote a proinflammatory state through microglioal activation, and induces this function of neural and precursor cell populations.
Immune dysregulated state that occurs result in neurotoxic astrocyte reactivity and dysregulation of oligodendroglial lineage and myelinization.
Patients who receive anthracycline based therapies may be at increased risk for memory problems and underlying brain injury and the affects persist several years beyond treatment conclusion.
Patients who receive anthracycline based therapies may be at increased risk for memory problems and underlying brain injury and the affects persist several years beyond treatment conclusion.
Symptoms are more frequent in patience who receive very high dose chemotherapy.
There is evidence of measurable neurocognitive effects among patients with Breast Cancer who were exposed to chemotherapy, however studies also suggest documented cognitive changes before any cancer directly therapies, as well as in association with other common breast cancer treatments such as with endocrine and radiation.
Cognitive impairment from chemotherapy can be long-lasting and limit quality of life and well-being.
Anemia increases the risk.
Radiologic changes with cognitive dysfunction not common on MRI.
May be a result of cerebral white matter changes.
BDNF and IL-6 might be involved in post-chemotherapy chemobrain and fatigue.
Chemotherapy is associated with neuroimaging evidence of diffuse brain injury, including vulnerability of the brain to degeneration.
Case reports of patients receiving high dose chemotherapy have shown MRI changes in water spaces of white matter areas.
No reported cases of cognitive dysfunction and white matter MRI changes with standard dose chemotherapy.
Women with breast cancer treated with adjuvant chemotherapy with CMF score lower on neuropsychological test 20 years after treatment and women never treated for cancer (Schagen SB et al).
Women treated with endocrine therapy may find down regulation of natural estrogen production or blocking of its activity through endocrine therapies associated with effects on cognition.
A randomized trial of endocrine therapy in breast cancer patients showed a meaningful patient reported cognitive decline 12 months after starting endocrine therapy with or without chemotherapy: these findings were present in both premenopausal and postmenopausal women.
Resembles depression, and patients may be misdiagnosed with a mood disorder.
It is a physiological disorder and not a psychological one.
Functional MRI studies reveal reductions in total brain volume and gray matter in patients who receive chemotherapy.
Changes in brain structure associated with chemotherapy correspond to cognitive changes on neuropsychological testing.
Chemotherapy associated with changes in the prefrontal cortex manifesting by decreased executive function.
Mechanisms for cancer related cognitive impairment may be related to increased systemic inflammation occurring in response to malignancy, as well as to chemotherapy, radiotherapy, and surgery.
Chronically elevated inflammation can lead to neuroinflammation that could result in neurotoxicity and increased oxidative damage.
Cancer related cognitive impairment vulnerabilities include aging and pre-existing medical conditions with cognitive risks such as diabetes or heart disease.
There may be increase vulnerability among APOE4 carriers.
Traditionally cancer related cognitive dysfunction has been attributed to chemotherapy.
Mechanisms to elucidate the pathophysiological basis of cancer related cognitive dysfunction include: a pro-inflammatory state within the CNS that results from cancer induced systemic immune responses and pro-inflammatory effects of chemo radiation, depletion of neural progenitor cells, neurotoxic affects of chemo radiation on neurons and glia, subcortical white matter changes, functional connectivity across cortical and sub cortical brain regions and neuropsychiatric symptoms such as anxiety and depression.
Microglia undergo therapy induced dysfunction of the hippocampus neural stem cells and the disruption of hippocampal neurogenesis through pro-inflammatory cytokines, such as interleukin 6.
22 to 41% of patients with non-CNS solid organ cancers experience cognitive decline compared with healthy patients, even before receiving cancer directed therapies.
There are a lung cancer induced anti-neuroantibodies that are related to cognitive impairments.
Cognitive impairments in patients with small and non-small cell lung cancer are frequent, occurring in 30% of individuals before treatment and in 39% of patients receiving chemotherapy.
There is a 40% incidence of cognitive impairment in breast cancer and a similar number in patients with melanoma.
37% of patients with lung cancer have been demonstrated to have anti-neural antibodies including antibodies against the neuronal cells surface.
Antibody associated cognitive impairments in patients with malignancy may result from indirect dysregulation of immune responses that target the CNS, the blood brain barrier, aberrant synaptic pruning, and direct effects of the antibody mediated synaptic dysfunction by diminished – methyl-D-aspartame receptor mediated currents or even neuron cell loss.
Patients with small cell lung cancer with neuronal antibodies have a 11 fold higher risk of cognitive impairment than patients without antibodies..