‘Cog-fog’ may indicate how untreated MS is likely to progress

Can we make better treatment decisions by spotting who is most at risk of disability progression? And if so, what should we measure to estimate risks? These were the fundamental questions asked by researchers who analysed data from over 1500 people with MSa who had received a placebob in four different clinical trials.1 The researchers wanted to know which of 19 different ‘baseline’ measurements made at the start of each trial best predicted the risk of disability progression.

Perhaps surprisingly, the level of cognitive impairment (or cog-fog)c was very important – even more so than the numbers of recent relapses and active lesionsd. Cog-fog is a common symptom of MS which can affect quality of life, leisure activities and ability to work. The other top predictors of disability progression were the total volume of all lesions and a self-assessment of physical health.

Can we measure cog-fog in a way that helps people with MS and their healthcare professionals make good decisions? Cog-fog is not generally used to inform treatment decisions, so this was the next question asked by the researchers.2 They established categories of ‘relatively low’ and ‘relatively high’ cog-fog, using a computer model that took into account the effects of age, physical disability and total lesion volume. Of those who received a placebo, the people with relatively low cog-fog generally experienced less disability progression than those with relatively high cog-fog.

The researchers concluded that a measure of cog-fog could give people with MS and their healthcare professionals an indication of how the disease is likely to progress if left untreated. This important information could be considered when making informed, shared decisions about treatment.

The importance of cognition also underscores the main focus of Brain health: time matters in multiple sclerosis: that the goal of treating MS should be to maximize lifelong brain health, cognitive function and physical function by minimizing disease activity.


The science behind the studies

The researchers used a meta-analysis, which combines the results of different studies to reveal overall trends. Assessing data from a large number of people makes it easier to tell the difference between genuine trends and those due to random chance.

b A placebo is a ‘dummy’ treatment with no therapeutic effect. Some clinical trials are set up to compare outcomes for people receiving a drug with those for people receiving a placebo. This new analysis pooled together data from people who received placebo in four trials to look at what happens when MS is untreated.

c In these trials, cog-fog was measured using the PASAT3 test, which evaluates processing speed, attention and concentration.

d Lesions are areas of acute damage that can be seen on an MRI brain scan. Some types of MRI scans use gadolinium as a contrast agent, in order to show only the ‘active’ lesions that have appeared or become larger recently.



1. Raghupathi S et al. Poster presented at ECTRIMS, 7–10 October 2015, Barcelona, Spain. Available from: http://onlinelibrary.ectrims-congress.eu/ectrims/2015/31st/115512/kartik.raghupathi.baseline.cognitive.function.predicts.clinical.disability.html?f=m2s546535 (Accessed 12 February 2016).

2. Sormani M-P et al. Poster presented at ECTRIMS, 7–10 October 2015, Barcelona, Spain. Available from: http://onlinelibrary.ectrims-congress.eu/ectrims/2015/31st/116356/maria.pia.sormani.use.of.individualized.cutoffs.for.baseline.cognitive.html?f=m2s65867 (Accessed 12 February 2016).

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