It’s 14 years since I received high doses of doxyrubicin and ifosfamide, along with two hormone interventions, for cancer. Unfortunately whilst the chemo wreaked havoc with my body – it didn’t touch the tumours and was stopped after 4 rounds. Aside from a total fog and whole brain-body anxiety it seemed to cause at the time (and one mildly psychotic episode where I tried to rid myself of canulas and pack my things to leave late in the night), I thought nothing of potential long term side effects from chemotherapy. I’d been reassured the blood-brain barrier protected my brain from all sorts of things.

It wasn’t until some 6 or 7 years later I first heard the term ‘chemo brain’, from a breast cancer survivor who confided she probably couldn’t hold down a full-time job again, even if she wanted to.

Not one to often look for the negatives, I assumed a few changes to my memory and organisational skills were more likely down to a long career break and a mind-numbing amount of long-term stress – I’d been ‘out of practice’ and it would soon come back with a bit of use.

I wonder if it’s ironic that I chose to study an MSc in ‘Memory and its Disorders’ in 2010? At the time, I imagined using it to help others in some way, but I was also very interested to see if the efforts it required would wake up some dormant parts of my own brain. It did and it didn’t.

Clearly, enough intelligence and mental apparatus remained for me to succeed, but despite the ‘practice’ it required, my ability to manipulate and organise information in my head seems severely compromised; And whilst I was a bit of a daydreamer at school, my increasing distractibility as well of loss of prospective memory, are some days both upsetting and crippling.

“Prospective memory” is a form of memory that involves remembering to perform a planned action or intention at the appropriate time.

(Lately I’ve been practicing a few interventions to help myself, but that’s a personal post for another day.)

Having been distracted enough to check out the chemotherapies I had in relation to chemo brain and finding grim news, I have, of course, been researching what I might do to prop up my brain and prevent further and premature decline! (Yet another distraction!) Useful enough though to share, so I’ve looked wider at the topic and I hope, distilled it into a few posts that might inspire other longterm survivors, to work towards brighter futures.

This is the first of three posts looking at chemo brain. In Part I, I explore what it is, what are its likely causes and then, drawing on the parallels with (the more advanced study of) the ageing brain suggest useful strategies for both rehabilitation and prevention of increasing problems. This week we’ll look at exercise and touch on learning.

Part II will explore a number of other lifestyle factors such as diet, sleep and mindfulness and their effects on brain function and in part III, have a look at strategies for tackling cognitive losses to improve quality of life. (I might need a fourth part to pull it all together in a summary of ‘Top Tips’ – for those of us who will have long forgotten what I said at the beginning!)

Most of this information should also be useful and interesting to anyone wanting to get the most out of an ageing brain in the future – prevention being always better than cure.

 

SO, WHAT IS CHEMO BRAIN?

Chemo brainis increasingly accepted as the name for a number changes to memory, concentration and the way we think that sometimes happens during and after chemotherapy.  Estimates on the number of adults affected vary greatly from 10-80%. The reason for this wide variation is because the effect seems to be drug type and strength-related.

The study of chemo brain is complicated because the loss of some cognitive function is also confounded by other factors typically affecting cancer patients such as: stress, depression and other drugs and treatments such as hormone therapies which are also known to affect cognition.

“Cognition” – is the process by which the sensory input is transformed, reduced, elaborated, stored, recovered, and used

For sometime, the medical community were consequently sceptical about its existence. However, in the last decade, the development of imaging techniques and other tests has enabled neuroscientists and neuropsychologists to observe and test subtle physical, chemical and behaviour changes in brain activity of people who have undergone chemotherapy.

Having identified some clear differences in these people’s brains, there has been a growing interest and understanding of this collection of mild to moderate neurological problems, now commonly called ‘chemo brain’, sometimes ‘chemo fog’ and – (..this one’s not taking off ->) ‘post chemotherapy cognitive impairment’ or PCCI.

The longer term hope is to be able to identify preventative or remedial measures to introduce at the time of treatment which might reduce nerve cell damage and also select or develop chemotherapeutic agents that are less neurotoxic.

Neuropsychological evaluation of adults complaining of chemo brain has confirmed a number of common cognitive deficits affecting memory, attention etc, varying in severity. The mechanisms behind the damage happening at cellular and DNA level is a relatively new area of study, so there isnt yet a full explanation as to why some people are more greatly affected than others.

“Neuropsychological Evaluation” – the testing of memory, attention, information processing, organisation skills, IQ etc with standardised statistically developed tests and instruments.

People affected by chemo brain describe a variety of sometimes debilitating and distressing symptoms such as:

  • Feeling foggy or ‘spacing out’.
  • Problems with remembering visual and spatial details, conversations, words or facts like names and dates.
  • Reduced ability to process complex information or to multitask – not being able to holdinformation in their head when thinking about some things.
  • Problems with prospective memory (remembering to do things in the future) and other organisational skills.
  • Impaired decision making.
  • Difficulty concentrating or focusing on one thing – having a short attention span and being more easily distracted.
  • Difficulty following conversations.
  • Being slower at certain tasks.
  • Struggling with relatively simple mental tasks like working out what cash you need for the three items in your shopping basket.

(In cancers of the central nervous system, more acute effects may result from a brain tumour, surgery and radiotherapy combined with the chemotherapy. And in children, whose brains are still developing, the effects of chemotherapy have been documented for longer and can be much more devastating with lowering of overall intelligence and other abilities.)

FURTHER INTEREST: Susan Guber, emerita professor of English at Indiana University and the author of “Memoir of a Debulked Woman,” writes a blog for the New York times. This post talks of her personal experience of chemo brain: Living With Cancer: Brains on Chemo 

 

DOES IT AFFECT EVERYONE?

Chemo brain seems more prevalent or marked in certain groups of patients and those receiving certain drugs. As a consequence, a fair proportion of research has looked at people undergoing the more aggressive chemotherapy treatments applied to hormone cancers (breast, endometrium etc) and cancers requiring stem cell or bone marrow transplant such as the lymphomas. However, there are now increasing indicators suggesting it does affect a wider population of chemotherapy patients, as imaging studies demonstrate clear changes to brain structures and patterns of brain activity, confirming neurological changes in a significant number of people.

For some individuals, the problems are short-lived but for others there are more long-term changes that at a one time, were dismissed as age or hormone-related but are now thankfully receiving increasing attention.

Whilst it is difficult to separate some of these issues to apportion the appropriate amount of blame to chemotherapy itself, there is much more acceptance and consensus that there are both short and long term effects of chemotherapy on cognitive function.

 

WHAT DOES THE RESEARCH SHOW?brain matter

Scanning studies have revealed reduced volumes of both grey and white matter in the brain in chemotherapy patients. Other studies have demonstrated reduced and changed blood flow in the brain. Both these occurrences provide some explanation for chemo brain. Whilst there have been studies suggesting these problems are greatly improved after a few years for some people (1), with physical differences reducing or disappearing, other studies have more worryingly, shown continued problems after many years.

The following studies give examples of these emerging issues, indicating the mechanisms behind chemo brain.

PET-imageReduced Blood Flow: A study at UCLA (2) used position emission topography (PET scans) to monitor the blood flow in brains of patients 5-10 years after chemotherapy whilst they completed memory exercises. This study suggested that these patients brains were having to work a lot harder than normal (compared to a control group who had not had chemotherapy). Part of the explanation for this was that these patients brains had a lower resting metabolism – as indicated by less blood flow to critical areas involved in thinking and mental processing (frontal cortex, cerebellum). Those that had had hormone therapy also had reduced blood flow to another part of the brain, called the basal ganglia which is an area responsible for bridging thought and action.

Chemotherapy is more toxic to nerve cells than previously thought: Observations of reduced white matter may be explained by animal studies at at the University of Rochester, New York (3) which have shown that chemotherapy drugs are even more toxic to precursor cells in the CNS than they are to cancer cells, causing both decreased cell division and cell death.

“Neurotoxic” – poisonous to nerves or nerve cells.

Another study, determined that not only does one commonly used chemotherapeutic agent (known as 5-FU) cause acute cognitive impairment but it also causes on-going degeneration to white matter tracts in the brain because it prevents the birth of new brain cells (called progenitor cells and non-dividing oligodendrocytes (4)). The research team concluded that intravenous treatment with 5-FU causes a syndrome of ‘delayed myelin destruction’ in the central nervous system. Myelin is the insulating layer on nerve fibres that gives white matterits colour. Its loss causes disruption of communication between nerve cells (neurons).

Reduced neurogenesis factors in the hippocampus: The hippocampus is part of the brain long-known to be responsible for helping you process new information into memory and work with spatial information. (You have two hippocampi – one in each brain hemisphere). The hippocampus has already received a lot of attention from memory researchers and consequently has been the focus of various studies into chemo brain. Its now known that this area of the brain is able to regenerate cells and grow extra ones in response to demands placed on it. Chemicals helping the hippocampus generate new neurons have been shown to be reduced in chemotherapy patients (5 & 6).

What can we conclude from these studies? The ‘Bad News’..

After chemotherapy your brain may be disadvantaged by loss of cells and in some specific brain areas, also suffer deficiencies in its ability to replenish those cells.

 

BUT IS THERE ANY GOOD NEWS?

Thankfully, Yes – There are two main neurological properties that give us hope for dealing with chemo brain, along with recent encouraging findings from the more advanced study of other conditions caused by loss of neurons, such as happens in both normal ageing and more markedly, in dementia:

These are Neurogenesis and Neuroplasticity

Neurogenesis hippocampus

You can add new cells to a key memory structure in your brain, called the hippocampus.

Not long ago we used to think the brain didnt develop new cells or neurons much past childhood so assumed that loss and damage to cells in the brain meant inevitable decline.

However the discovery of neurogenesis (new cell growth) in the the hippocampus has led to studying what encourages regeneration in the hope of identifying strategies to slow the effects of ageing and even prevent some dementias.

A bit like a muscle, parts of the hippocampus grow in response to heavy use. A good example of how intense learning can affect its growth comes from Maguire and Woollett from University College London. They scanned brains of novice London cab drivers before, during and after their training and compared the scans with the drivers’ success on the end test. (It can take 2-3 years to memorise enough material to succeed at the knowledge’). There was no difference in hippocampus size before the training started but after training, those that passed the test had bigger hippocampi (7).

FURTHER INTEREST: Elizabeth Gould – How Does Experience Influence the Brain? – YouTube  (Professor Gould outlines the main functions of the hippocampus and talks about her labs most recent work).

 Neuroplasticity

The second neurological property, of your brain, key to improving cognitive function is its neuroplasticity – this means that your brain is adaptable and is able to change and develop throughout life.

Individual connections within the brain are constantly being removed or recreated, largely dependent upon how they are used. Your brain can sometimes reroute around sparse neural pathways and get the job done anyway. The more you stretch yourself, the better the results as working at something will reinforce the new pathways, thereby improving your ability. It is recognised that the more you work at something the stronger neural connections become.

Neuroplasticity is widely therefore recognised as an essential part of learning and memory, as well as recovery from brain damage such as traumatic brain injury and stroke. Recovery seen in people with brain injuries and stroke don’t arise because the damaged parts of their brain re-grew – they recover abilities and function when their brain has found another way round the ‘problem’.

Neuroplasticity will also slow the effect and onset of diseases caused by neural degeneration such dementia.

 

The Study of Ageing and Dementia – what can this tell us?

In normal ageing there also tends to be a loss of some white matter and hippcampal volume in the vast majority of adults (8). There are some subtle gender differences in the areas affected and the severity of decline has been shown to be linked to a number of factors. In general, exercise, a healthy diet (rich in antioxidants and omega 3 fatty acids), level of education and staying mentally and social active are all protective against cognitive decline.

Research also shows that the principles of neuroplasticity and neurogenesis are key factors to maximising both the number of neurons you have and also maximising the use you get from the ones that are left, as you get older.

The hippocampus, essential for memory, is known to deteriorate with age and more markedly so in the dementias. Consequently a lot of memory research has looked at it with an interest in the mechanism of neurogensis to determine strategies for maintaining the hippocampus – and therefore memory – into old age.

As some of the physical loss and cognitive issues with chemo brain are similar issues identified with ageing of the brain, it makes sense that, if you can support your brain to limit and repair some of the damage of ageing, there’s hope that similar efforts will prop up your chemo-damaged neurons too.

FURTHER INTEREST: Professor Lorraine Tyler – The Resilient Brain: Cognition and Ageing – YouTube. (British Psychological Society Annual Lecture)

 

Exercise Dance

Theres overwhelming evidence that exercise, particularly aerobic exercise (such as dancing or walking at a pace that makes you slightly breathless) for 30 minutes at least three times a week increases white and grey matter and hippocampal volume in the elderly, whether they show signs of cognitive decline or not (9). Studies suggest that exercise is likely to slow down the progression of dementia and prevent it in others.

couple-walkingSimilarly, if we might be missing some white and grey matter, even hipppocampal volume after chemotherapy – exercise is an obvious remedy to build in as a lifelong commitment to reduce and remediate for this loss.

2_bikersSome of the explanation for the benefit for exercise may lie in the increased blood flow and therefore oxygen and nutrients to all parts of our body, including our brain but there are clearly other more complicated processes of repair initiated by exercise, at a genetic level, that are only just being discovered. One example is the production of a hormone called Irisin, discussed in the following article:  Exercise link to ageing process « Jersey Evening Post.

FURTHER INTEREST: New York Times article – What Sort of Exercise Can Make You Smarter? 

Short of time? Interval training maybe the answer BBC’s Dr Michael Mosley says ‘fast exercise’ is even more powerful than experts thought | Mail Online.

Learning and mental activity

The study of learning in normal ageing shows that stretching and exercising your ‘mental muscle’ will not only help you maintain abilities better but also continue to develop neuroplasticity into your 90’s. And the more ‘plastic’ your brain the better it deals with neuronal loss. It appears that some older adults cope better, cognitively, into old age due to this flexibility.

Additionally, this is why two people seeming to have similar damage from events like a stroke, may have markedly different recovery paths.

We know the benefits of learning are usually quite specific – practicing suduko, for example, will only improve your suduko not your memory, as popular media reports a few years ago suggested (though it may add some beneficial variety, rather than more television!)

rep_photo-2However, practicing complex and variable skills are more likely to influence abilities on other similar skills – this is why ‘variety is the spice of life’ and you may have heard advice to take up new hobbies, musical instruments and learn a new language as a way of preventing dementia. I know a clinical psychologist, nearing retirement – he and a colleague have been ‘competing’ for years on who undertakes the most novel evening class each year – just for this reason!

We also know from rehabilitation programmes for stroke and brain injury that it is important to practice lost skills, repeatedly, to get the brain working at finding ways round problem areas. So to make significant progress you will have to practice properly and repeatedly.

Inevitably therefore your motivation and interest in improving a skill are key to success.

So, if you want to be more organised you have to practice being more organised. If this is a skill you never had before (you may, like me have been able to rely on your memory in the past, to turn up to events on time etc) you may have to start at the beginning, with the basic props like ‘To Do’ lists and calendars along with a commitment to structuring your time and reviewing your progress until you have formed a new habit.

images-2We’ll take a more detailed look at specific strategies for helping manage the common issues of chemo brain, in a future post.

 

SUMMARY

Research into chemo brain confirms a phenomenon of cognitive losses caused by chemotherapy, affecting a wide range of people, both in the sort and long term.

Scans show a loss of white and grey brain matter and hippocampal volume in people complaining of chemo brain. The exact mechanisms behind this are still being determined but cell death at the time of chemotherapy and longer term damage to the brain’s ability to reproduce and maintain its neurons, are implicated as likely causes.

However, there is hope. The good news is that brain is not a static organ as we once thought and is able to regenerate parts of the hippocampus known to be essential for memory, visual and spatial skills etc. Additionally, the brain is flexible throughout life and with work, can learn new tricks as well as find its way around problems.

Furthermore, studies into ageing reveal that there is much you can do to minimise neuronal loss with regular aerobic exercise and mental activity.

NEXT TIME IN PART II: A LOOK AT OTHER LIFESTYLE FACTORS, THEIR IMPACT ON THE BRAIN AND COGNITION AND HOW THEY MIGHT HELP CHEMO BRAIN

 

 

REFERENCES

(1) Inagaki M., Yoshikawa E., Matsuoka Y., Sugawara Y., et al. (2006). Smaller Regional Volumes of Brain Gray and White Matter Demonstrated in Breast Cancer Survivors Exposed to Adjuvant Chemotherapy. Cancer, 109 (1): 146-156.

(2) Silverman D.H., Dy C.J., Castellon S.A., et al. (2007) Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy. Breast Cancer Res Treat 103:303–311.

(3) Dietrich J., Han R., Yang Y., Mayer-Pröschel M., Noble M. (2006). CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. Journal of Biology, 5:22.

(4) Han, R., Yang, Y.M., Dietrich, J., Luebke, A., Mayer-Pröschel, M., and Noble, M. (2008). Journal of Biology, 7:12

(5) Mustafa, S., Walker, A., Bennett, G., & Wigmore, P. M. (2008). 5-flouracil chemotherapy affects spatial working memory and newborn neurons in the adult rat hippocampus.  The European Journal of Neuroscience, 28 (2): 323-330.

(6) Seigers, R., Schagen, S. B., Beerling, W., Boogerd, W., et al. (2008). “Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat.” “Behavioral Brain Research”, 186 (2): 168-175.

(7) Woollett, K., and A. Maguire, E.A., (2011). Acquiring “the Knowledge” of London’s Layout Drives Structural Brain Changes  Current Biology (21 (24): 2109-2114)

(8) Piquet O., Double K.L., Kril J.J., Harasty J., MacDonald V., McRitchie D.A. and Halliday G.M. (2009). White matter loss in healthy ageing: a postmortem analysis. Neurobiology of Ageing. 30 (8): 1288-95

(9)Larson E.B., Wang L., Bowen J.D., McCormick W.C., Teri L., Crane P., Kukull W. (2006) Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Annals of internal medicine. 144(2), 73-81.

Advertisements