Chemotherapy for breast cancer can impair cognitive functioning ("chemo brain" or "chemobrain"). Chemo brain is characterized by reduced verbal ability, impaired decision making, faulty short-term memory and other deficits. Chemo brain is the result of brain damage, much of which heals over time but some of which might persist.

Symptoms of chemo brain

Approximately one-third to one-half of women undergoing chemotherapy for breast cancer experience chemo brain during treatment and for some time afterwards. Studies using standard psychological testing have reported that chemotherapy reduces verbal ability, slows cognitive processing speed, impairs executive functioning, and reduces psychomotor processing speed. Cognitive processing speed refers to the ability to automatically and fluently perform relatively easy or routine cognitive tasks, especially when high mental efficiency (i.e., attention and focused concentration) is required. Executive functioning refers to the ability to organize thoughts and prioritize tasks, manage time well, make plans, and adapt to changing situations. Psychomotor processing speed refers to reaction time when a physical task is involved. It involves the coordination of a sensory or cognitive process and a motor activity.
The symptoms of chemo brain include slowed thinking and decision making, trouble remembering or spelling common words, problems with short-term memory and concentration, and reduced ability to multitask. There are glitches in the brain's operations. Unconscious mistakes can occur in tasks that are simple and routine. Typing and spelling errors may become common and all written work has to be checked for errors. Chemo brain can feel like moving through a fog, where the outlines of thoughts are indistinct and it's difficult for ideas to fully form. Conscious thinking itself can become more difficult, so that it takes effort to complete a thought or come to a conclusion.

Chemo brain is caused by brain injury

Researchers initially assumed that chemo brain did not involve actual physiological brain damage, in part because it was thought that chemotherapy did not cross the blood-brain barrier. Instead, the cognitive symptoms reported by women were studied as though they were primarily a consequence of depression or other emotional responses to breast cancer diagnosis and treatment. However, it has now been established that chemotherapy drugs can cause measurable brain damage in breast cancer patients. In fact, recent evidence suggests that cancer itself results in cognitive impairment, for reasons that have not been determined.
Breast cancer patients who have undergone chemotherapy have been shown to have reduced (1) activation in the left middle dorsolateral prefrontal cortex and premotor cortex; (2) left caudal lateral prefrontal cortex activation; (3) hippocampus size; and (4) white matter integrity compared to controls.
Studies that have compared women's brains before and after chemotherapy have reported (1) reduced left caudal lateral prefrontal cortex activation; (2) injury to white matter (likely reflecting a combination of axonal degeneration and demyelination); and (3) reduced gray matter density in bilateral frontal, temporal, and cerebellar regions and right thalamus.
A study of mice who were treated with CMF (methotrexate, cyclophosphamide, and 5-fluorouracil) chemotherapy demonstrated that methotrexate disrupted the formation of new nerve cells in the brain. Another study reported that rats treated with Adriamycin (doxorubicin) experienced significant declines in functional connectivity between the bilateral primary visual cortex and the right forelimb somatosensory cortex, and the right and left superior colliculus.

How long does chemo brain last?

Chemo brain normally starts to improve within one year of treatment and the improvement continues for an additional one to two years. However, some of the brain damage appears to be permanent. As mentioned above, chemotherapy can disrupt the formation of new nerve cells (neurogenesis) in the brain. Although there is some disagreement among researchers, neurogenesis appears to occur throughout adulthood and is controlled by cell cycle regulators. The hippocampus, a brain region important to memory and learning, is a primary site of neurogenesis. Chemotherapy drugs that act by inhibiting cell cycle progression appear to produce cognitive impairment by disrupting neurogenesis in the hippocampus. This means that neurogenesis can start to repair some of the damage caused by chemotherapy once treatment ends. The perception of being in a fog lifts and problems with short-term memory and executive functioning appear to resolve within one to five years of the end of treatment. However, problems with verbal fluency and psychomotor processing speed can persist long afterwards.

Long-term effects of chemotherapy on cognitive functioning

One Dutch study investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with continued cognitive performance deficits more than two decades after treatment. CMF was the standard breast cancer chemotherapy from the 1970s to the 1990s. The study included 196 women with breast cancer who had been treated with CMF chemotherapy between 1976 and 1995 and a control sample of women never diagnosed with cancer. The average time since treatment was 21 years. Neuropsychological tests were used to compare the two groups. Women who had been treated with endocrine therapy (tamoxifen or aromatase inhibitor) or who had experienced a breast cancer recurrence were excluded from the study. Results were adjusted for age, level of education, and depression.
The women who received CMF chemotherapy were found to perform worse on cognitive tests than matched controls. The differences in performance were subtle and occurred primarily in word learning, memory and information processing speed. The breast cancer survivors also had lower scores on psychomotor speed (coordination of thinking and hand movement). The magnitude of the effects was comparable to approximately six years of age-related decline in cognitive function, according to the authors.

Risk factors for chemo brain

Not all women experience chemo brain, however predicting which women are most susceptible is difficult. There is some evidence that pre-existing systemic inflammation, old age, low cognitive reserve and depression each are associated with increased magnitude of the cognitive deficits associated with chemotherapy. Cognitive reserve refers to the difference between the cognitive performance predicted by an individual's level of brain pathology or injury and that individual's actual performance. In other words, those whose measured cognitive performance is better than predicted have high reserve, whereas those who perform worse than predicted have low reserve. This information does not appear to be particularly useful for determining who would be most susceptible to chemo brain.
Breast cancer patients can also adopt coping strategies designed to address specific chemo brain symptoms. First, it might be helpful to know that while chemo brain is unpleasant, it does not affect all areas of intelligence and it is to a great degree temporary. To address specific chemo brain symptoms, women can make lists and keep detailed calendars to organize their lives, become more systematic in their daily routines, check all their work or other written output, and prepare more thoroughly for business meetings or travel. In other words, women can take advantage of the more lucid times to organize and set up for the times when thinking is more difficult and less reliable. Getting enough sleep (to facilitate the brain's memory storage and housekeeping functions) could be important.

Preserving brain health in old age

Generally speaking, rates of cognitive impairment increase with age. However, individuals vary considerably and genetic heritage is only part of the reason. The following factors increase the likelihood of cognitive impairment in old age: depression; lack of exercise; diet high in saturated fat, trans fats and/or sugar; exposure to cadmium; high levels of systemic inflammation; diabetes; high blood pressure; and high cholesterol. Maintaining satisfying social connections and a healthy lifestyle might protect against cognitive decline in some women. One important 2023 study reported that regular multivitamin use is associated with reduced cognitive decline in old age, however it is not clear how it affects possible long-term effects of chemo brain.

Endocrine treatments can also impair cognitive functioning

Tamoxifen and aromatase inhibitors can also cause some of the symptoms of chemo brain in some women. However, this appears to be the result of brain estrogen deprivation, not outright brain damage. The symptoms caused by estrogen deprivation appear to improve within a year after endocrine treatment ends. Women who undergo radiotherapy can also experience chemo brain-like symptoms. While the reasons for this have not been explained, these symptoms also appear to be temporary. One major 2021 study found no links between use of endocrine treatments in non-metastatic breast cancer and risk of subsequent dementia.

Does chemo brain lead to Alzheimer's disease?

Although the evidence is mixed, chemo brain does not appear to lead directly to Alzheimer's disease in old age. Several studies have examined the question as to whether breast cancer patients have a higher risk of developing dementia in old age:
  • A major 2023 Swedish study did not find an association between breast cancer diagnosis and treatment and risk of eventual all-cause dementia, vascular dementia or Alzheimer's disease. However, when analyzed by age at diagnosis, the data showed that women diagnosed with breast cancer after age 65 had a greater risk of all-cause dementia and vascular dementia.
  • A large prospective study that included 62,565 U.S. breast cancer patients who were at least 65 and free of cognitive impairments at diagnosis reported that the risk of developing Alzheimer's disease, vascular dementia, or other dementias was lower in patients who received chemotherapy for breast cancer.
  • Another study of older U.S. breast cancer survivors (2,913 of whom received chemotherapy and 18,449 who did not) reported that chemotherapy was not associated with a greater risk of the development of dementia over time for any of three age groups: 66 to 70, 71 to 75, or 76 to 80.
  • A study that included 18,360 older women diagnosed with Stage II, III, or IV breast cancer found that there were significant differences at baseline between individuals who received and did not receive chemotherapy. In the first few years after breast cancer diagnosis, dementia was more common in women who had not had chemotherapy, probably reflecting group differences at baseline.
On the other hand, in the long term, diagnoses of Alzheimer's disease and other types of dementia are more common in women who have been treated for breast cancer than in the general population. In addition, women who are at higher genetic risk for Alzheimer's disease (APOE4 genotype) may be more likely to experience chemo brain.

Strategies for coping with chemo brain

One small 2022 study reported that a probiotic supplement taken during treatment significantly reduced chemotherapy-related cognitive impairment. There are no proven drug treatments for chemo brain once it occurs. Regular exercise and other physical activity have been shown to improve executive function, information processing speed and concentration in women with chemo brain in some studies. Cognitive and memory training have been shown to improve cognitive function, memory, verbal functioning and orientation/attention, although studies are inconsistent.

Foods that help protect the brain

A wide variety of foods have been shown to have neuroprotective properties, in part by reducing oxidative stress in the brain. Generally speaking, high fruit and vegetable intake has been shown to be associated with better cognitive functioning in cancer survivors. Below are foods that have been demonstrated to have neuroprotective effects while at the same time having the potential to protect against breast cancer.
Please read the applicable food pages when making your own food lists since these pages contain important advice, consumption limits, and other pertinent information.
Alcohol can increase neural damage, as can exposure to bisphenol A (BPA), phthalates, and heavy metals such as cadmium, mercury and lead. Diets high in saturated fat, trans fats and/or sugar have been found to be associated with cognitive decline. The soy isoflavones genistein and daidzein have been shown to induce neurotoxicity at high concentrations and should not be taken as supplements. One study reported that mice fed a diet supplemented with canola oil showed signs of memory impairment compared to mice on a regular mouse chow diet. Another study reported that high habitual caffeinated coffee intake (greater than 6 cups per day) was associated with lower brain volume and increased odds of dementia.
High blood pressure, high cholesterol and high blood sugar also can harm the brain. Recent evidence suggests that use of probiotics could help prevent and improve chemo brain since chemotherapy is associated with unfavorable changes in the gut microbiome.

Sources of information provided in this webpage

The food lists and other information above, which are updated continually as new research becomes available, have been developed based solely on the results of academic studies. Clicking on any of the foods will take you to its webpage, which contains specific information concerning that food's relationship to breast cancer, including its overall recommendation, as well as links to supporting studies.
Below are links to 20 recent studies concerning chemo brain. For a more complete list of studies, please click on chemo brain.