Cognitive impairment in MS affects risk assessment: what impact does this have on prognosis?

More bad news for MSers. MS impairs or ability to assess risk. Does this affect MS prognosis? #MSBlog #MSResearch

“Apologies for posting yet again on cognitive function in MS; I am aware that some of you find this topic depressing. However, without keeping our feet on the ground and realising how serious a disease MS how do we take the field forward?”

“This study shows that decision-making processes are impaired in MSers and are linked to MRI markers of gray matter damage. Drawing on my iceberg analogy there clearly more going under the surface that is seen using conventional MRI. What is interesting is that this study shows that MSers who have problems with decision making have difficulty adjusting to levels of risk rather that than showing increased impulsivity. If this correct MSers may on average under estimate the risk that MS poses to them as an individual and play down their own need for more effective treatments. This raises issues in relation to mental competency of MSers in making informed decisions about risk that involves them self. I have always assumed that the reason why people with rheumatoid arthritis (RAers) are in general prepared to take greater personal risks with highly effective therapies, compared to MSers, was down to rheumatologists being more persuasive, and earlier adopters, than MSologists. May be I have gotten this wrong, maybe it is MS that is making MSers risk adverse due to the cognitive impact of the underlying disease?”

“This research paper demonstrates how subtle the cognitive effects of MS can be. It would be interesting to know how these deficits in decision making affect performance in the job market? Are MSers who have deficits in decision making more likely to become employed than those who don’t? Decision making is core to what makes us human and competitive; this is a cognitive task that is vital for optimal occupational and social functioning. How can we simply sit back and accept this fate? Can we prevent the impact MS has on cognition? Can I propose that the preservation of decision-making abilities another reason to promote early effective treatment in MS? To achieve this MSers will have to accept early treatment with highly-effective treatments when they are still well with no overt disability. If you wait until you have disability it may well be too late.”

“This is yet more evidence that MS is a dementing illness.”

Muhlert et al. Impaired decision-making and diffusion orientational complexity in people with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Sep;84(9):e1.

OBJECTIVE: Difficulties with decision-making have been reported in MSers. It is however unclear what aspect of decision making is impaired, for example whether they are more impulsive, and how any impairments relate to grey matter pathology. In this study they assessed grey matter microstructure using a novel measure of the number of diffusion orientations on diffusion MRI “diffusion orientation complexity (DOC)”. They studied DOC in cortical areas known to be associated with decision making and looked at its associations with performance on the Cambridge Gambling Task (CGT).

METHOD: One hundred and five MSers (61 RR, 26 SP, 18 PP; mean age: 45.9 years) and 36 healthy controls (mean age: 39.6 years) were studied. Decision making performance was assessed using the CGT. T1-weighted (T1w) scans (1x1x1mm) and cardiac-gated diffusion scans (2x2x2mm, 61 directions at b=1200s/mm2, 7 at b=0) were acquired on a 3T system. T1w images were registered to diffusion scans and segmented to extract GM. GM regions with a priori evidence of an association with decision-making (caudate, hippocampus, middle frontal gyrus, anterior cingulate, medial prefrontal cortex; all bilateral) were masked using the Oxford-Harvard template and mean DOC was measured in these GM regions.

RESULTS: On the CGT, MSers showed less adjustment of bets to account for the level of risk (t-test, p<0.01) and were significantly slower at making decisions (p=0.01). MSers also showed significantly lower DOC in the caudate (p><0.01), the middle frontal gyrus (p><0.001), the anterior cingulate (p<0.01), and the medial prefrontal cortex (p=0.001), and significantly higher DOC in the hippocampus (p><0.05), relative to controls. In MSers , risk adjustment correlated with hippocampal DOC (r=-.23, p><0.05), the length of deliberation correlated with medial prefrontal DOC (r=-0.22, p><0.05) and the quality of decision-making correlated with DOC in the anterior cingulate (r=0.34, p=0.001). 

CONCLUSION: Decision-making deficits in MSers relate to difficulties in adjusting to levels of risk rather than increased impulsivity. Changes in decision-making correlate with DOC in grey matter regions associated with those functions, suggesting a relationship with abnormal grey matter microstructure, such as loss of neurites, which is known to occur in MS.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • Prof G, your stance on early and aggressive treatment is wearing thin. What can you offer those with established disease? What can you offer those in the throes of progressive MS? Nothing, right?

    Your early and aggressive mantra should be restricted to neophyte MSers and pharmaceutical sponsored conferences. Those of us with established disease have been abandoned by this blog. The only thing we hear about is research, but we've been hearing about this lousy research for decades without any benefit. The situation for people like us is terrible.

    In all honesty I don't care any more. You can plug your DMT propaganda as much as you want and litter the posts with the same old, same old. I give up. It's not as if neurology has been able to do much for me other than make money from my un fortunate situation.

    No wonder most of us don't care about commenting on posts anymore.

  • Well, this is unpleasant news, but I don't agree that bad decision making is behind MSers aversion to risk. I think it's lack of a clear message from the people who educate us about our disease–from our neurologists to the national agencies (National MS Society in my case).

    I was in a chat room the other day with a bunch of MSers who have had the diagnosis a lot longer than me. They were advising me that DMTs do NOT stop relapses; they slow disease progression. I pushed back a little, but they insisted that I was wrong, and I didn't feel like arguing.

    The idea that we can aim to be disease activity free, and should expect our neurologists to aim for that too, is completely news to them. Heck, it might even be news to some neurologists. So, a relapse while on Interferon or Glaterimer seems quite acceptable to most MSers. They're not risk averse, they're just going with the information they have.

  • Prof G,

    You know when to kick a man when he is down! The bad news just keeps on coming. I've never felt so low thanks to you. You're the opposite of an anti-depressant. A King Midas gone wrong. My positive thinking has been completely undone by the constant barrage of grim news – early death, unemployment, dementia. You'd better buy some shares in Dignita as your postings have increased the sales of one way air tickets to Switzerland. You're the best salesman they have! From your 25 years of research, is there a glimmer of hope for us who have missed the window of opportunity for early / aggressive treatment. Please can you change the top of the apge to "A blog for which shares bad, and even worse, MS research news". A logo and e-mail address for Dignitas would also be helpful. Does any other reader of this blog want to join me on a one way drive down to beachy head? Does anyone know of any oter MS research blogs which occassionally post some hopeful news e.g. 100-1 chance that a re-myelination therapy might become available. I'm not looking for miracles, jsut a tiny, tiny glimemr of hope that all the hudnreds of millions spent on MS research might make our lives a little better in the future.

    • If you don't like the fact that this blog posts ALL information pertaining to MS, you are free to go elsewhere. As it is I suspect the majority would prefer to be appraised of all the facts rather than adopting the ostrich/Pollyanna approach.

    • Free to go elsewhere? There is no elsewhere…..this blog is undoubtedly the best in cyberspace. The U.S. has nothing close to this blog. It seems neuros and researchers have realized that once progression has set in there is little that can be done besides symptom management. What MS and other neurodegenerative diseases need is someone to take the first step in regenerative medicine. Unfortunately the litigious environment in the U.S. prevents this leap forward. Until then research will continue as before.

  • How much of this cognitive impairment is due to the cocktail of drugs being dished out to patients desperate for a cure? I'm glad I didn't have Prof G as my Neurologist when I was diagnosed, because I would never have had such a fabulous career.

  • There seems to be no EXIT strategy for DMT.

    Let me explain.
    Most MSers know that DMT doesn't work for every patient equally well.
    Most MSers also know that the Neurologist doesn't know in advance which patient will benefit from the drug.
    Most MSers also know that it is not quite clear to the Neurologist when to STOP prescribing the drug.
    Most MSers also know that quite a few MSers become more ill, sometimes seriously ill, with than without a drug.
    Most MSers also know that quite a few MSers are extremely relieved when they finally decide to stop taking the drug and feel much much better.

    It should be clear who will benefit from a drug and it should also be clear who won't benefit from a drug.
    As long as this information is not available why should MSers in their right mind start taking DMT?

    So I would like to ague that MSers are making informed decisions about risk involved.
    Well informed MSers read the posts written by the MSers who decided to stop their treatment.

    • "Most MSers also know that quite a few MSers are extremely relieved when they finally decide to stop taking the drug and feel much much better."

      There are also many MSers I've spoken to who feel much better after taking the drug. Many said that their lives had been transformed for the better when taking Tysabri to give one example. There are also many who have had great results with alemtuzumab too.
      "It should be clear who will benefit from a drug and it should also be clear who won't benefit from a drug.
      As long as this information is not available why should MSers in their right mind start taking DMT?"

      Because you won't know if you don't try and if it doesn't work there are alternatives.

      So, well informed MSers should read the posts written by Msers who have decided to continue their treatment.

    • trial and error

      So, well informed MSers should read the posts written by MSers who have decided to continue their treatment as well as the posts written by MSers who have decided to discontinue their treatment. And what the side effects were they were suffering from.

    • I don't really need to read the posts of people who have decided to discontinue their treatment because I know how it works out for them. We have natural history studies to see where that goes.

    • I really don't get your point. It all depends on the DMT being used. If it's beta interferon, I think most of us know its side effects- flu like symptoms, injection site reactions. What do you mean- more harm than good? If you continue to relapse, its not working for you, so you stop taking it and try something else. That's your EXIT STRATEGY. You need to be more specific.

    • The induction therapy with mitoxantrone is a good approach (follows on from our mouse tolerance induction studies of a few years back where we used transient T cell depletion before re-establishment of tolerance).
      I think Mike Boggild had success with this approach when he was in Liverpool.

    • The exit strategy is sometimes complicated by the possibility of rebound effects. I know there is a lot of contradictory evidence from differing trials on what happens when one stops tysabri.

      What has struck me in the past talking with MSers at dinners was the lack of understanding comparative risk. I am JC+, and on Monday I will go in for my 80th infusion. I know the odds are somewhere between 1 in 300 and 1 in 400 that I may get PML. The odds are a little fuzzy as the population who have been on the drug this long is small. Still people I speak with are shocked I would stay on despite the JC+ result. When I point out Tysabri lets me keep a full time job and continue to help raise our medically fragile foster kids people sound surprised. Still, it's only when I point out the morbidity rate of the recommended treatment for the most treatable kind of cancer being roughly 1 in 200 that people begin to understand why I would take such a risk. (Mastectomy followed by chemo for breast cancer caught early is the cancer and treatment to which I am comparing.)

      Most understand when I give comparisons of risk, but was it MS masking their understanding before I spelled it out or just general lack of knowledge? For my work, we've had people estimate the square footage in their business and their selling space. The number of times I have had people say their store was 80 square feet with half of it being selling space is scary. Can you imagine a department store the size of your desk? Many just don't understand or cognitively grasp basic numbers.

  • Prof G, I sense the followers of this blog are revolting against the years of 'momentous' promises you gave and now they feel betrayed at knowing that their diseases' most probably won't improve because either they have missed out or have an existing progressive MS malady. This early and aggressive mantra isn't applicable to where they are coming from. All these years of waiting and there is nothing to show. Even the Bank of England is promising green shoots but you guys only offer handfuls of mud. MS research has been a momentous waste of time for most of us. I don't care about future generations of MSers, I worry about now.

    DMTs will fall by the wayside. We need neuroprotective treatments that give remyelination hopes to all MSers, but you guys fail to perform. The MS Societies' are making fortunes and giving us nothing. Governments are penalising us massively and MS remains a disease that is merely swept under the rug. From 2015 most of us will lose out on PIP because MS isn't deemed bad enough because of its fluctuating nature.

    No more donations. No more campaigning. I resign. I will hope for the best but plan for the worse. Thanks for nothing.

    • "Even the Bank of England is promising green shoots but you guys only offer handfuls of mud."

      Green shoots need something to grow in, that's where the mud comes in.

  • I am advising all early diagnosed MSers to get a neurologist who will give them DMTs whether or not they have current systems. Risk averse can't apply to us older offered us any treatment!

  • Prof G said there were 4 treatment hurdles- 1.stop inflammation, 2.neuroprotection,3. remyelination and 4.neurorestoration. It looks like the newer effective treatments deal with 1. There are trials going on with 2. at the moment I think with simvastatin and amiloride which may help progressive MS.
    Dr Franklin and Prof Ffrench Constant(?)have done translational research with 3., but I'm not sure if there are any trials yet, and 4. is decades away at the moment.
    Bearing in mind that it was only within the last 20 years that we began to get drugs to treat MS, we've come a long way. Hopefully there will be neuroprotective agents available within the next 10 years that will stabilise progression (if the NHS can afford them)

    • "Hopefully there will be neuroprotective agents available within the next 10 years that will stabilise progression (if the NHS can afford them)"

      I am extremely hopeful that that will be the case.

  • Health And Safety Consultant Norfolk (Link removed) Saturday, November 30, 2013 2:59:00 am

    That's why I suggest people do mental work as much as they can. More mental work the better the gray matter will become. Thank you for sharing the report with us.

    Arnold Brame

By Prof G



Recent Posts

Recent Comments