Chemotherapy is generally considered one of the most successful methods for treating cancer and is widely used to control and cure many cases. However at the same time it is not without its symptoms and some of these can be highly frightening and unpleasant – and this is especially true of the effects it can have on our brain functioning. Here we will look at how chemotherapy works to attack cancer cells, how this affects our brain and what the side effects are that you should expect.
How Chemotherapy Works
Chemotherapy treatments will vary depending on the specific case and individual, but they use the same principles to operate. To understand how this works, it is important to understand a little about the life cycles of our cells and in particular cancer cells work.
Essentially our cells go through a certain life cycle at the end of which they go through mitosis – splitting to become two new cells and replicate their DNA. In the case of cancerous cells this spread is particularly fast and aggressive and the DNA that's being copied is mutated. This then causes faulty cells to spread in a specific area until that organ is damaged beyond repair.
Chemotherapy is a generalized term that describes the use of chemicals to target these cells before they can split (chemo = chemical). Chemotherapy prevents the spread of cancer by attacking cells in a particular phase – usually those in the 'M' phase that are dividing or the 'S' phase that are just about to divide and this can then prevent the spread of cancer. However the downside of this is that it can't discriminate between cancerous cells that are dividing and healthy cells that are dividing. Thus not only are cancerous cells in danger of being destroyed – so too are other cells that are going through the process of dividing – and those cells with shorter life cycles that spend more time in this stage are more likely to be destroyed in large numbers.
Depending on the kind of cancer however the chemicals used in chemotherapy will vary and will attack the cells at different precise phases. In some cases the chemotherapy drugs may even attack cells in the G0 phase (the resting stage) which is the furthest stage from the M phase. Thus the type of healthy cells damaged here will be different from those damaged by other chemotherapy drugs and the symptoms will vary accordingly.
Among the side effects caused by this process is what's known as 'chemo brain'. This is a term for a range of cognitive issues that many cancer survivors report experiencing during and after their chemotherapy treatment suggesting long term cognitive impairment caused by the chemotherapy. It is more formally known as 'chemotherapy-induced cognitive dysfunction' or post-chemotherapy cognitive impairment (PCCI). This effects around 20-30% of patients and has several unpleasant side effects including:
The link between chemotherapy and cognitive impairment has been demonstrated in a weight of recent research and is accepted by physicians and scientists. However the exact cause of chemo brain is unknown, and a topic of much discussion.
Interestingly some forms of cancer are more likely to cause chemo brain than others, and in particular breast cancer is most likely to cause chemo brain (it occurs in roughly 10-20% of cases). This has helped researchers to identify some possible causes of chemo brain. There is a relatively small amount of research on the topic though, and this is partly due to the difficulties inherent in studying chemo brain – largely caused by confounding factors such as depression and sleep loss which can also cause similar side effects.
Here we will address some possible causes:
Causes of Chemo Brain
Direct Impact of Chemotherapy on the Brain
It has been suggested that chemo brain effects may be caused by the direct effects of the chemotherapy on the brain. However the chemotherapy is unlikely to affect the neurons directly for several reasons.
• There are some cells in the human body that get 'locked' into the G0 phase and never come out of it. This phase, the resting phase, is the phase at which the cell exists and does not get closer to reproduction. Neurons – the cells of the brain – are an example of such cells and it was believed until relatively recently that we cannot create new brain cells past a certain age; though more recent studies have revealed neurogenesis (the birth of new brain cells) to be possible under certain circumstances. Cells permanently in the G0 phase are called 'postmitotic cells' (postmitotic meaning after mitosis). Thus, there should be no damage to the brain cells unless you have chemotherapy for cells in the G0 phase which is unusual.
• Even if this were the case, in many instances the large molecules used in chemotherapy are too large to cross the 'blood-brain-barrier' meaning that they never make it from the blood stream into the brain in order to damage the neurons therein.
However that said, some chemotherapy treatments are designed to treat brain tumors and these will of course be delivered directly into the brain. These include interstitial chemotherapy which involves disc-shaped polymer wafers that are implanted into the cavities where tumors have been removed surgically; intrathecal chemotherapy which involves chemotherapy injected directly into the spinal fluid; intra-arterial chemotherapy which delivers high doses of chemotherapy into the brain using catheters; and CED (convection-enhanced delivery) which involves catheters into the brain tumor itself. Some systemic chemotherapy drugs may also pass from the bloodstream into the brain.
Processes such as intrathecal chemotherapy can cause many of the side effects associated with chemo brain and particularly if they should cause a leak into other areas. Still the above is not an entirely satisfactory explanation for most cases of chemo brain as the majority of cases are reported in breast cancer – and these do not use these delivery methods and so likely will not affect the brain through the blood brain barrier.
Meanwhile, the hippocampus is a region in the brain that plays an important role in memory and is one of the only areas to demonstrate neurogenesis – meaning it may be more likely to be effected by agents that could cross the blood-brain barrier. Studies have shown that when given to rats, 5-fluorouracil (a commonly used agent), could reduce the amount of 'brain-derived neurotrophic factor' which is required for neurogenesis.
More likely to explain the majority of cases of chemo brain are the hormonal changes that come about as a result of chemotherapy and in particular the reduction of estrogen which has many important roles in the brain. This is supported by the fact that those suffering from breast cancer are likely to experience such cognitive problems before they have received any chemotherapy. In some cases chemotherapy can actually induce the menopause and this too can cause problems with memory and concentration.
At the same time chemotherapy can alter other hormones include those that affect the brain and mood, as well as those that impact the brain such as melatonin.
While there are some motor-coordination and visual impairments listed among the symptoms of chemotherapy, these may not occur as a result of damage to the brain. One study found that around 30% of patients treated with 5-flourouracil experienced ocular toxicity.
Free radicals are a by-product released by many chemotherapy drugs which can damage cells around the body and in the brain. They are highly implicated in cases of dementia and Alzheimer's and thus they could be responsible for some cognitive decline post-chemotherapy.
Treatment for chemo brain has not been widely researched, however there are some potential treatments that may help. Antioxidants for instance may be used in order to prevent damage from free radicals and these can be taken as supplements or as part of a diet. Fish oils are a particularly good source of antioxidants which can also improve neurotransmission. At the same time it has been suggested that the use of cognitive behavioral therapy and an attempt to remain mentally active may also help to prevent cognitive decline. The use of stimulant drugs may also help to reduce chemo brain symptoms. For instance methylphenidate has been used to treat the problem in women with breast cancer, and Modafinil has proven successful in some trials (Modafinil has been approved for narcolepsy and is an awakeness-promoting substance). Finally estrogen supplementation may help to prevent and even reverse some of the side effects in women with breast cancer, but is not recommended as it can cause other complications including the potential exacerbation of the existing cancer.