Once we have hit our mid 20s, brain atrophy or brain shrinkage is just a normal process of aging, it happens to us all. There are many theories on why this happens, and there can be different factors that may affect the rate at which our brains lose volume.
On average we lose between 0.5% and 1% of our brain volume per year this varies from person to person, however for people with MS this can be slightly higher. Measuring the rate of brain atrophy is slightly challenging, it requires regular high quality MRI scans and complex calculations to work out the volume of the brain and the amount that it changes over time.
However, the extra challenge may be worth it as brain atrophy maybe be very informative and give more information over and above other MRI readouts such as the location and size of brain lesions. While lesions are routinely used as a marker, their number, size and location do not always correlate with the disability someone might have or develop.
It is very important that we have good markers to predict disease course and accurately monitor disease to help prevent the accumulation of disabilities and halt the progression of disease activity.
A group of international scientists, from the UK, Europe and the US have been investigating brain atrophy in people with primary progressive MS. Their research has recently been published in the scientific journal Annals of Clinical and Translational Neurology.
In this study they used the control (untreated) population of a clinical trial evaluating fingolimod in progressive MS (known as the INFORMS trial). Using this population takes advantage of all the in-depth data previously collected on these 487 people with primary progressive MS, including multiple MRI images of their brains and clinical observations.
During the study these people showed low levels of inflammation in the brain as determined by new or growing lesions seen by their MRIs, despite their disability continuing to progress. They also had a low level of relapses, however their MRIs did reveal evidence of previous substantial inflammatory activity.
However, when the scientists looked at the rate of brain loss they discovered that there was a relationship between the amount of brain volume lost and disability progression. Those who experienced the greatest loss of brain volume ended up with more marked disability and disease progression at the end of the study period. These results suggest there is a relationship between brain volume loss and disease progression in people with primary progressive MS. This is consistent with data from those with relapsing remitting MS.
In this study, the lack of active inflammation as shown by MRI lesions in people with primary progressive MS suggest that brain volume loss is not dependent on levels of inflammation in the brain. This potentially explains why some anti-inflammatory treatments which have been successful in relapsing remitting MS have not been so successful in primary progressive MS.
One of the challenges facing the development of medications for primary progressive MS is the lack of markers which can be used in clinical trials to determine whether any intervention is working or not. Results from this study, reinforce the notion that new lesions or growing lesions as seen by MRI are not suitable markers for primary progressive MS. Instead, brain volume measurements might be at least in part a suitable marker to help us speed up the discovery of new drugs to treat progressive MS. Other research is also ongoing that indicates that brain volume loss in specific parts of the brain may be even more sensitive markers for disease progression than whole brain volume.
Researchers at the Brain and Mind Centre at the University of Sydney are particularly interested in this field, and MS Research Australia funded neurologist and PhD Scholar, Dr Heidi Beadnall to examine the best ways to quantify brain tissue loss in normal clinical practice and to improve the conduct of clinical trials for progressive MS. You can learn more about Dr Beadnall’s research here.