Ms. Zhao is 65 years old, usually lively and cheerful, clean and articulate. Six months ago, she was found to have early stage breast cancer during a medical checkup, so she underwent surgery according to her doctor’s requirements and had 6 cycles of chemotherapy after surgery. However, recently, Ms. Zhao felt that she could not concentrate on her work, she liked to forget things, and her hands and feet were not sharp. Sometimes she thinks of a word to use and knows what to say, but she can’t say it, as if the pathway from her brain to her mouth is broken. She also said, “I can’t even smile, I don’t have expressions, I have feelings inside but I can’t transmit them to the outside world, it’s like trying to find a way through a fog.” Her daughter thought it was Alzheimer’s, so she took her to the hospital for a checkup, and the diagnosis was unbelievable: Ms. Zhao was suffering from “chemo brain”. So, can chemotherapy also cause brain damage? Cancer is a local manifestation of a systemic disease, and the biggest threat to patients is the spread and metastasis of cancer cells. Chemotherapy is the most advanced treatment method in cancer treatment in recent years, and its popularity is due to the fact that unlike surgery and radiation therapy, it is a holistic treatment for the human body, acting on the whole body through oral and intravenous administration, thus effectively controlling the spread and metastasis of cancer cells. Chemotherapy is known to cause side effects such as nausea, vomiting, hair loss and a drop in white blood cells. Recently, a study published by American scientists showed that about 60% to 80% of cancer patients have problems with memory, learning ability, attention and other brain functions months or even years after chemotherapy. Therefore, chemotherapy-induced cognitive dysfunction should also be of great concern to the public. 1. What is chemotherapy brain? The so-called chemotherapy brain refers to the impairment of memory, learning ability, attention, reasoning ability, executive ability, concentration, spatial sense or other cognitive functions that patients experience during or after chemotherapy. The main clinical manifestation is cognitive dysfunction such as memory loss. 2.How is chemo brain formed? At present, the cause of chemotherapy brain is not well understood. It may have a direct or indirect effect on the central nervous system or cognitive ability of cancer patients through the following effects (1) Chemotherapeutic drugs damage the nervous system Most commonly used chemotherapeutic drugs do not readily cross the blood-brain barrier. However, genetic changes alter the structure of transporter proteins on the blood-brain barrier, thus allowing small amounts of chemotherapeutic drugs to enter the brain parenchyma. In particular, patients carrying inefficient DNA repair mechanism alleles and inefficient efflux pump alleles are susceptible to the occurrence of chemo brain, and even the use of small doses of chemotherapeutic drugs can cause damage to structures associated with cognitive abilities in the brain, thus inducing death and reduced cell division in this fraction of cells. Chemotherapeutic drugs crossing the blood-brain barrier can not only produce neurotoxicity directly damaging the central nervous system, but also reduce cognitive function by damaging microglia, oligodendrocytes and neuronal axons and by post-demyelination, as well as altering the water content of brain tissue and neurotransmitter levels. In addition, studies have shown that some chemotherapeutic agents, which are cell growth inhibitors (e.g., fluorouracil, carmustine, cisplatin, and cytarabine), can damage CNS progenitor cells and oligodendrocytes, and that fluorouracil causes delayed myelin destruction. The toxicity of chemotherapy on CNS progenitor cells may be the main cause of delayed persistent neurotoxicity. (2) Chemotherapy-induced endocrine changes Hormonal changes induced by chemotherapy, which can also induce menopause, can have an indirect effect on impaired cognitive function in cancer patients, mainly caused by a decrease in the level of neuroprotective estrogen. Thus, patients with prostate and breast cancers receiving hormone therapy may have impaired cognitive function due to decreased estrogen or testosterone levels. Several studies have shown that estrogen and testosterone have antioxidant and neuroprotective effects, and that estrogen plays an important role in maintaining telomere length. This suggests that the secondary decrease in hormone levels caused by hormones alone as monotherapy, even without chemotherapy, may lead to chemo brain. (3) Chemotherapy-induced oxidative stress Chemotherapeutic drugs that cause DNA damage affect the central nervous system thereby increasing levels of oxidative stress. Oxidative stress is mainly caused by an imbalance of reactive oxygen products, including free radicals and peroxides. Several studies have shown that chemotherapy can cause a decrease in antioxidant capacity and point mutations within the mitochondria, which can lead to cognitive decline. In addition, the increase of oxidative stress by-products induced by chemotherapy can also affect the cognitive function of patients by damaging and interfering with the small vessels and blood perfusion mechanisms of the central nervous system. (4) Chemotherapy-induced tumor-associated anemia Tumor-associated anemia is a common complication of tumor and/or chemotherapy that can cause a range of debilitating symptoms, including impaired cognition, visual memory loss, and executive impairment, by reducing the oxygenation of the brain, thus severely affecting the quality of life of tumor patients. (5) Chemotherapy-induced immune dysregulation Recent studies have shown that chemo brain may also be caused by immune dysregulation, i.e., the tumor and/or chemotherapy causes the body to release inflammatory factors (such as interleukin-1, interleukin-6 and tumor necrosis factor) that can cross the blood-brain barrier. This effect was more pronounced in patients treated with interleukin-2 and interferon alpha. Cytokine levels were significantly higher in these patients, but with a corresponding reduction in executive and spatial capacity and prolonged response time. This shows that cytokine levels are closely related to the cognitive ability of tumor patients. 3. What are the symptoms of chemotherapeutic brain? Studies have shown that chemo brain symptoms in most patients will last for 1 to 10 years after chemotherapy, but some patients will have such symptoms all the time. Common symptoms of chemo brain include: difficulty in concentrating and thinking clearly; frequent errors when completing more than two tasks at the same time (difficulty in multi-tasking); shorter time to concentrate; easy confusion, especially with newly learned knowledge or information; feeling that one’s thinking and memory are confused; decreased spatial reasoning ability and spatial cognitive ability; decreased memory, especially from visual or Information obtained from the sense of hearing, such as what had been talked with someone or what had been seen is easily forgotten. Some patients describe the symptoms of chemo brain as a “brain fog” or “high” state, as if you have drunk too much alcohol but are not yet drunk, you try to admonish yourself to stay awake, but your mind is still drowsy. 4.How should chemo brain be treated? When symptoms of chemo brain appear, the first thing to do is to know that these problems are not all in your brain and give yourself more time to think about them, while most people will have significant relief after a period of time; secondly, tell your specialist as soon as possible so that they can analyze other causes of the symptoms and adjust the current treatment plan. To date, there is no definitive drug that can combat chemo brain. Studies have confirmed that some recognized neuroprotective factors (such as methylphenidate, modafinil, diphenidate, and the cholinesterase inhibitor donepezil) are effective against chemo brain. Studies have shown that methylphenidate can improve impaired cognitive function in oncology patients. Psychostimulants have been used to treat cancer-associated fatigue as well as cancer-associated cognitive hypofunction. Modafinil is a new generation of neurostimulants that may have the effect of altering certain cognitive functions associated with chemotherapy in oncology patients. The role of antioxidants in the prevention and treatment of the chemotherapeutic brain deserves attention. Studies have shown that high-dose vitamin E can prevent and improve chemotherapy brain in oncology patients by scavenging free radicals. In addition, non-pharmacological interventions such as psychosocial support and cognitive rehabilitation may improve chemotherapy brain-associated cognitive decompensation. 5.How to prevent chemo brain? Although there is no specific drug for chemo brain, we can reduce its occurrence if we pay attention to prevention. To prevent chemotherapy brain, we may want to start with the following: (1) Ensure sufficient sleep and improve sleep quality. Carry a notebook or smartphone with you to keep track of important information and things to do and dates; focus on one thing at a time and don’t try to dual-use or multi-task. (2) Learn some techniques to reduce stress in your life. Stress is an important risk factor for cognitive impairment, especially for those who are chronically stressed, who are more likely to form plaque in the blood vessels of the brain and are therefore more likely to develop symptoms of cognitive impairment. (3) Develop good habits of using the brain. Brain function is not used, do some games that require the brain, or engage in a new hobby and learn a new language is good for thinking and memory. (4) pay attention to physical exercise. Some studies have shown that active physical activity can play a role in preventing cognitive impairment, and its effect is better than other measures. The reason for this is that exercise lowers blood pressure, controls cholesterol levels, and generates new brain cells. (5) Healthy diet, drinking coffee and green tea can reduce people’s risk of developing cognitive impairment. Studies have shown that older adults who regularly consume highly concentrated cocoa beverages have improved performance on cognitive function tests because chocolate contains flavonoids, a powerful antioxidant that removes harmful molecules from the body and protects healthy, normal molecules when the body is in its older stages. (6) Take care of good oral hygiene. A British study showed that older people with gum disease were two to three times more likely to have memory problems compared to those with little or no gum disease.