Chemotherapy for breast cancer can cause reduced 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 appears to persist for decades.
While there are no specific treatments for chemo brain, breast cancer survivors can adopt several strategies to address its symptoms.
Symptoms of chemo brain
At least one-third 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 would be most susceptible is not possible. There is some evidence that 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. Turmeric has been shown to protect the brain from various types of injury and could possibly reduce the magnitude of chemo brain. It might also be helpful to avoid the factors listed in section below that are known to contribute to cognitive impairment in old age.
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; 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.
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.
- Açaí berries
- Arctic char, wild
- Beans, black
- Bell peppers
- Black cumin
- Brussels sprouts
- Currants, black
- Grapes, red and muscadine
- Green tea
- Honey, min. processed
- Hot peppers
- Lake trout
- Lettuce, romaine
- Olives and olive oil
- Pistachio nuts
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. A 2021 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.
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 ranking), 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.
Selected breast cancer studies
Effects of sleep disturbances and circadian rhythms modifications on cognition in breast cancer women before and after adjuvant chemotherapy: the ICANSLEEP-1 protocol
Elia C, de Girolamo L, Clarisse B, Galin M, Rehel S, Clochon P, et al. Effects of sleep disturbances and circadian rhythms modifications on cognition in breast cancer women before and after adjuvant chemotherapy: the ICANSLEEP-1 protocol. BMC Cancer. Springer Science and Business Media LLC; 2023; 23 10.1186/s12885-023-11664-x
Early change in fatigue, insomnia, and cognitive impairment and symptom severity at 3-years post-treatment in breast cancer survivors
Lee RM, Rash JA, Seal M, McCarthy J, Garland SN. Early change in fatigue, insomnia, and cognitive impairment and symptom severity at 3-years post-treatment in breast cancer survivors. Research Square Platform LLC; 2023; 10.21203/rs.3.rs-3581028/v1
The disproportionate burden of Alzheimer's disease and related dementias (ADRD) in diverse older adults diagnosed with cancer
Schiaffino MK, Schumacher JR, Nalawade V, Nguyen PTN, Yakuta M, Gilbert PE, et al. The disproportionate burden of Alzheimer's disease and related dementias (ADRD) in diverse older adults diagnosed with cancer. Journal of Geriatric Oncology. Elsevier BV; 2023; 14:101610 10.1016/j.jgo.2023.101610
Longitudinal cognitive function and brain metabolites in women receiving chemotherapy for stage 1 to 3 breast cancer: Observational study
Beyer J, Couch R, Ruddy KJ, Zeydan B, Tosakulwong N, Lesnick TG, et al. Longitudinal cognitive function and brain metabolites in women receiving chemotherapy for stage 1 to 3 breast cancer: Observational study. Medicine. Ovid Technologies (Wolters Kluwer Health); 2023; 102:e35524 10.1097/md.0000000000035524
Effect of Physical Exercise on MRI‐Assessed Brain Perfusion in Chemotherapy‐Treated Breast Cancer Patients: A Randomized Controlled Trial
Koevoets EW, Petr J, Monninkhof EM, Geerlings MI, Witlox L, van der Wall E, et al. Effect of Physical Exercise on MRI‐Assessed Brain Perfusion in Chemotherapy‐Treated Breast Cancer Patients: A Randomized Controlled Trial. Journal of Magnetic Resonance Imaging. Wiley; 2023; 10.1002/jmri.28967
Açai Berry Ameliorates Cognitive Impairment by Inhibiting NLRP3/ASC/CASP axis in STZ-Induced Diabetic Neuropathy in Mice
Impellizzeri D, Siracusa R, D'Amico R, Fusco R, Cordaro M, Cuzzocrea S, et al. Açai Berry Ameliorates Cognitive Impairment by Inhibiting NLRP3/ASC/CASP axis in STZ-Induced Diabetic Neuropathy in Mice. Journal of Neurophysiology. American Physiological Society; 2023; 10.1152/jn.00239.2023
The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA).
Albers E, Kieffer J, Schagen S. The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA).. Research Square Platform LLC; 2023; 10.21203/rs.3.rs-3156121/v1
Menopausal hormone therapy and dementia: nationwide, nested case-control study
Pourhadi N, Mørch LS, Holm EA, Torp-Pedersen C, Meaidi A. Menopausal hormone therapy and dementia: nationwide, nested case-control study. BMJ. BMJ; 2023;:e072770 10.1136/bmj-2022-072770
Differences in total cognition and cerebrovascular function in female breast cancer survivors and cancer-free women
Downs TL, Whiteside EJ, Foot G, Mills DE, Bliss ES. Differences in total cognition and cerebrovascular function in female breast cancer survivors and cancer-free women. The Breast. Elsevier BV; 2023; 69:358-365 10.1016/j.breast.2023.03.018
Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial
Yeung L, Alschuler DM, Wall M, Luttmann-Gibson H, Copeland T, Hale C, et al. Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial. The American Journal of Clinical Nutrition. Elsevier BV; 2023; 10.1016/j.ajcnut.2023.05.011
Risk of All-Cause Dementia, Alzheimer Disease, and Vascular Dementia in Breast Cancer Survivors
Wennberg A, Ding M, Feychting M, Modig K. Risk of All-Cause Dementia, Alzheimer Disease, and Vascular Dementia in Breast Cancer Survivors. Neurology: Clinical Practice. Ovid Technologies (Wolters Kluwer Health); 2023; 13:e200173 10.1212/cpj.0000000000200173
Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis
Hiensch AE, Beckhaus J, Witlox L, Monninkhof EM, Schagen SB, van Vulpen JK, et al. Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis. Journal of Cancer Survivorship. Springer Science and Business Media LLC; 2023; 10.1007/s11764-023-01392-3
Plasma levels of interleukin‐6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study
Mandelblatt JS, Small BJ, Zhou X, Nakamura ZM, Cohen HJ, Ahles TA, et al. Plasma levels of interleukin‐6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study. Cancer. Wiley; 2023; 129:2409-2421 10.1002/cncr.34784
Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors
Ahles TA, Schofield E, Li Y, Ryan E, Orlow I, Patel SK, et al. Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors. Journal of Cancer Survivorship. Springer Science and Business Media LLC; 2023; 10.1007/s11764-023-01365-6
Cognitive function and breast cancer molecular subtype before and after chemotherapy
Hsu Y, Chen H, Wu S, Tzang B, Hsieh C, Weng Y, et al. Cognitive function and breast cancer molecular subtype before and after chemotherapy. Applied Neuropsychology: Adult. Informa UK Limited; 2023;:1-8 10.1080/23279095.2023.2176233
Association between Endocrine Therapy and Cognitive Decline in Older Women with Early Breast Cancer: Findings from the Prospective CLIMB Study
Baltussen JC, Derks MG, Lemij AA, de Glas NA, Fiocco M, Linthorst-Niers EM, et al. Association between Endocrine Therapy and Cognitive Decline in Older Women with Early Breast Cancer: Findings from the Prospective CLIMB Study. European Journal of Cancer. Elsevier BV; 2023; 10.1016/j.ejca.2023.02.008
Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities
Holland TM, Agarwal P, Wang Y, Dhana K, Leurgans SE, Shea K, et al. Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities. Neurology. Ovid Technologies (Wolters Kluwer Health); 2022;:10.1212/WNL.0000000000201541 10.1212/wnl.0000000000201541
Impacts of breast cancer and chemotherapy on gut microbiome, cognitive functioning, and mood relative to healthy controls
Bilenduke E, Sterrett JD, Ranby KW, Borges VF, Grigsby J, Carr AL, et al. Impacts of breast cancer and chemotherapy on gut microbiome, cognitive functioning, and mood relative to healthy controls. Scientific Reports. Springer Science and Business Media LLC; 2022; 12 10.1038/s41598-022-23793-7
Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer’s-type neuropathology
Karanth SD, Katsumata Y, Nelson PT, Fardo DW, McDowell JK, Schmitt FA, et al. Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer’s-type neuropathology. Brain. Oxford University Press (OUP); 2022; 10.1093/brain/awac035
Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE
Fernandez HR, Varma A, Flowers SA, Rebeck GW. Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE. Cancers. MDPI AG; 2020; 12:3842 10.3390/cancers12123842