Lifestyle and Huntington's disease

18 March 2019

CROSSWORD-NEWSPAPER

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Reading, playing chess or learning a new language may help to slow degeneration in Huntington's disease...

Alongside Alzheimer’s and Parkinson’s Disease, Huntington’s is a neurodegenerative disorder. These diseases are all caused by the death of specific groups of nerve cells in the brain, leading to progressively worsening symptoms. In the case of Huntington’s disease, patients usually have problems with movements, thinking, and emotions. The symptoms usually begin by the mid-forties and tend to become more severe as the disease progresses, ultimately leaving the patient bedridden and dependent on others by the final stages.

Huntington's gene

Although neurodegenerative disorders share many characteristics, Huntington’s disease is unique in one way: we know what causes it. In 1993, scientists found a change - or mutation - in a gene on chromosome 4 that leads to Huntington’s disease. In patients with the condition, this region, which was referred to initially as IT15 (interesting transcript 15) and latterly as the huntingtin gene, contains an abnormally long repetition of the three genetic letters, CAG. The healthy form of the gene naturally contains a small number of these so-called trinucleotide repeats, but if more than 40 are present, the individual will inevitably suffer from Huntington’s disease.

This means that people who have a parent with this disorder have the possibility of being tested to find out whether they too will develop the disease. This, of course, is not an easy decision since there is no cure for Huntington’s disease at the moment. Some people who do get tested and find out that they will develop Huntington’s disease decide to collaborate in scientific studies, making it possible to study the neurodegenerative process in its earliest stages, including while patients are still pre-symptomatic. This also means that Huntington’s is useful  for studying neurodegenerative processes in general, since it can provide information that is relevant for other diseases which also involve the death of brain cells.

Intellectual lifestyle

It's often claimed that doing crosswords keeps dementia at bay. Unfortunately, it is not that simple, since there are many factors that can influence the risk of developing dementia, including genetic predisposition. However, there is evidence that maintaining an active cognitive lifestyle throughout life can reduce cognitive decline. This has been observed in studies on ageing and dementia, where years of education, work complexity or the level of engagement in intellectual leisure activities appears to have an effect on the risk of developing dementia. So does this include a genetic disease like Huntington’s - is it possible that lifestyle can also play a role in this case? Research has shown that, although a higher number of CAG repeats is associated with an earlier onset of the disease, this accounts for only about 50-60% of the variability in age at onset. This means that 40% of this variability could be caused by environmental factors. So, even in a genetic disorder like Huntington’s disease, our environment can play a key role in how the disease manifests.

In line with this, previously a group of researchers at Ramón y Cajal Hospital in Madrid, Spain, had found that those patients with Huntington’s disease who had studied for more years tended to present with less severe clinical symptoms once the influence of age and their number of CAG repeats was taken into account. In another study, this time carried out by researchers at the Cleveland Clinic in Ohio (USA), patients with a higher level of intellectual activity showed a slower rate of cognitive decline and brain volume loss over time.

In our team at the Cognition and Brain Plasticity Unit from the University of Barcelona, we were interested in further investigating the effect of an intellectual lifestyle on how Huntington’s disease progresses. To do this, we used a summary score that took into account a person's number of years of education, their occupation, the number of languages they spoke, their reading activity and musical education, and how often they took part in intellectually-challenging games like chess or Sudoku. We found that, at the same disease stage, patients with more intellectual lifestyles not only did better in cognitive tests but also showed a delay in the appearance of the first symptoms of Huntington's compared to what would be expected based on their number of CAG repeats.

We also found that patients with higher levels of intellectual activity showed a reduced loss of volume in the striatum, the main brain area affected by Huntington’s disease. And besides brain volume, we also found that the level of intellectual activity influenced the communication between the brain regions that form part of a brain network involved in planning and setting goals. So our results suggest that keeping an active cognitive lifestyle could help to slow neurodegeneration and delay its deleterious consequences in Huntington’s disease and other disorders.

Brain plasticity

You may be wondering how this is possible. How can exercising our brains help to delay cognitive symptoms? Studies on mice show that a rich environment in cages that have new and complex toys and allow social interactions, which would be the rodent equivalent of an intellectual lifestyle – can lead to improved neural functioning, to the formation of new connections between neurons, and even the birth of new neurons. This reflects an important property of our brains: its plasticity. We know that the brain is not immutable to its surroundings. Instead the opposite is true. Our environment and lifestyle shape our brains, strengthening connections which are used repeatedly over time and pruning away those which are seldom used. In this sense, our brains are malleable and we can change our environment in a way that is beneficial for us.

Clinical applications

So what these results actually mean for the life of patients suffering from Huntington’s and other neurodegenerative diseases? Although it is still early to know the potential implication of these findings, they suggest that cognitive interventions could be useful in order to delay the appearance of symptoms or slow their progression. However, it is difficult to know to what extent this delay may be relevant in practice. Other environmental factors, such as diet, levels of physical activity and drug use may play a role too. In practice, interventions in which all these aspects are taken into account, together with medication, have the best chances of making a difference in patients’ lives.

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