Barts-MS rose-tinted-odometer: zero-stars

What do you say when I colleague chastises you for stating the fact that MS is potentially a ‘preventable dementia’? This particular colleague was clear that there is no need to draw any parallels between MS and other neurodegenerative diseases because of the negative connations that the term dementia has. I had to remind him that MS ticks all the boxes for being classified as a dementia; i.e. (1) MS is an acquired and not a congenital disorder; (2) MS is a chronic progressive disease; (3) MS impacts on multiple cognitive domains and (4) MS impacts on social and occupational functioning. Have I missed something?

I also had to remind this colleague that almost every neurology or psychiatry textbook included MS on its list of causes of dementia. I am not prepared to peddle alternative facts because pwMS may find it distressing to find out that if MS is left to its own devices it will shred their brains and cause dementia. Please note the rose-tinted-odometer is set to zero for this post. 

The small study below reiterates what we already know that both relapsing and progressive patients have cognitive problems that correlate with physical disability. This study also confirms that T1 hypodensities or blackholes on MRI, particular in the thalamus (a deep grey matter structure in the brain) predicts cognition problems. T1 hypodense MS lesions or black holes, or at least a proportion of them, have been shown to be very destructive and include lesions with so-called phase-rims (iron around them) and a subset we call SELs (slowly expanding lesions). Some neuroradiologists often describe an MS brain with a high volume of black holes as being similar to Swiss cheese in reference to Emmental cheese. 

Now for the good news is that these studies below are on patients with significant end-organ damage and if we can diagnose and treat MS effectively early on we can prevent or at least delay the end-organ damage and the progressive loss of cognition. This is why we have spent years promoting the concepts of ‘Time-is-Brain’, ‘Treat-2-Target of NEDA’, ‘Rapid escalation’, ‘Flipping-the-Pyramid’, ‘Brain Health’, ‘Beyond-NEDA preventing end-organ damage’, ‘Holistic Management’, ‘Marginal Gains’, etc. Buried in all of these concepts is the use of effective DMTs to prevent end-organ damage and to prevent dementia. 

I am very pleased that my pwMS in Australia have taken this one step further and launched their own awareness campaign, albeit sponsored by Biogen, to raise awareness about early effective treatment ( The campaign is been run by a group of MS social media influencers. I met them all virtually last year and spoke to them about the concepts that underpin our  ‘Brain Health: Time Matters’ policy document. It would be great if pwMS across the world could do a similar thing. 

Do you agree with my colleague above that we should try and protect pwMS from the harsh realities of MS and what can happen to their brains if we don’t manage their MS appropriately? Or should we peddle false facts and a rose-tinted view of the world?

de Paula Gois et al. Associations between cognitive and clinical disability across MS subtypes: The role of the underlying brain damage. Mult Scler Relat Disord. 2020 Dec 19;48:102701. 

Background: Cognitive impairment (CI) is present in all stages and subtypes of multiple sclerosis (MS). However, the majority of studies examined relapsing-remitting (RRMS) patients, and did not address cognitive phenotyping. Is still not clear whether patients with progressive MS (PMS) have a distinct pattern of CI compared to RRMS. In addition, there is conflicting data regarding the correlation between clinical and cognitive disability.

Objective: To investigate the differences of CI between PMS and RRMS patients, evaluating cognitive phenotypes. We also aimed to analyze the association between physical and cognitive disability with MRI measures of grey-matter atrophy and lesion burden.

Methods: Thirty patients with PMS and twenty-four with RRMS underwent neurological, neuropsychological (BRB-N, Boston Naming, and Tower of London), and MRI assessments (3T). Brain volume evaluations were performed using FreeSurfer. Principal Components Analysis on neuropsychological yielded six principal cognitive domains. Cognitive deficits were classified according to three categories: no CI, impairment in isolated cognitive domain, or impairment in combined domains.

Results: In the overall sample, the most frequently impaired cognitive domains were information processing speed (IPS) and visual memory. PMS patients had a higher prevalence of verbal memory and verbal fluency deficits, and more frequent impairment in combined cognitive domains compared to RRMS individuals. After multivariable regression analysis with clinical variables, EDSS was associated with most cognitive domains. Nevertheless, after including T1-lesion volume in the model, it was the most consistent predictor of cognitive performance. To further analyze the interaction between EDSS and T1-lesions, we performed GLM analysis with EDSS and T1-hypointense lesion volume as covariates, and T1-lesion volume adjusted better the model for verbal memory (p = 0.013), IPS (p = 0.021) and total number of impaired cognitive domains (p = 0.021).

Conclusions: RRMS and PMS patients tend to have a similar neuropsychological profile in general, but the extent of CI was greater in PMS patients. Worse cognitive performance was associated with increased physical disability, but this correlation was no longer significant after controlling for T1-lesion volume, suggesting that the underlying MS pathology might be involved in this relationship. Thalamic and T1-lesion volumes were the most consistent MRI predictors associated with cognitive disability.

CoI: multiple

Twitter: @gavinGiovannoni                                         Medium: @gavin_24211

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.


  • I don’t think people should be shielded from the reality of what MS does to the brain. I’m always an advocate of educating yourself about your own condition, and gathering as much info as possible. This approach is often frustrated by health practitioners, however (such as not being given blood test results. And when asking to see MRI scans being asked why (because it’s MY brain!). Those of us with MS can do much to improve our own brain health: thank you for your commitment to educating us. I’d like to claim that homeschooling is an excellent brain workout…but

  • A lot of people with MS already know that time is brain, but are prevented from accessing treatment in the U.K. as they “do not meet” the criteria set out in the guidelines for prescribing DMT or have no DMT available to them. I hope this changes in the future. Even after meeting the criteria, it took a year for me to be offered a DMT and that was with me asking about them.

  • Yes, the term “preventable dementia” does bring with it a whole heap of negative connotations. So, use another term instead which fits equally well – call it a preventable “acquired brain injury”. MS also just happens to tick the boxes on this one, and it doesn’t have quite the same degree of negativity that the word dementia always seems to carry with it.

    “The term Acquired Brain Injury (ABI) is used to describe all types of brain injury that occur after birth. The brain can be injured as a result of:
    – traumatic brain injury (TBI)
    – stroke
    – brain tumour
    – poisoning
    – infection and disease
    – near drowning or other anoxic episodes
    – alcohol and drug abuse”

    How familiar does this little list sound to any PwMS?
    “Changes as a result of an acquired brain injury can include:
    – Medical difficulties – (epilepsy)
    – Altered sensory abilities ( impaired vision , touch , smell )
    – Impaired physical abilities – (weakness, tremor, spasticity)
    – Impaired ability to think and learn ( forgetful , poor attention)
    – Altered behaviour and personality ( short tempered, lethargic, flat or depressed)
    – Impaired ability to communicate ( slow or slurred speech , difficulty following conversation)”
    (From )

    So, split the hairs, bite the bullet, grab the bull by its horns, and change the terminology away from “dementia” (even if that term is also technically correct) and an increased degree of traction for the Time is Brain catch-cry and all of the companion slogans will probably be the result.

    Signed – a person with hypoxia-caused ABI and MS – and no way to tell which bits that don’t work too well were caused by which problem…………….

  • What can those of us with SPMS do to slow down the Swiss cheese effect? as I understand it there aren’t any treatments accessible on the NHS, is that correct? But are there other things, do you think?
    Thanks as always

    • Not quite correct. Siponimod has recently been licensed for active SPMS and is now available on the NHS. The problem is that the current definition of active SPMS is quite narrow. I don’t agree with this definition as most pathology studies of SPMS shows that MS is active despite no recent superimposed relapses and/or focal MRI activity.

      • Thanks for your reply, and glad to read of your recovery in a different thread. Do you think it’s possible to get access to Siponimod if you don’t fit the narrow criteria you mention? it’s frustrating (understatement!) to know that finally there might be something that could help only to not qualify for it.

  • The issue I have is that some people may make assumptions that all pwMS have MS dementia. This would be discrimination and ableism.
    I know a manager at my work would question my ability to do certain jobs. They have been this way to me already, even though my MS is invisible. So now I don’t mention to my managers and colleagues my MS.

    • Please note a “preventable dementia” is not “dementia”; if you treat MS effectively you don’t have to develop cognitive impairment.

  • I read this with great interest, as my cognition has been declining in recent years and it’s been quite a frustrating experience. I was diagnosed in 1992 and didn’t begin any DMTs until about 4 years post-diagnosis (as they weren’t nearly as available as they are today). In the past 3-4 years, physical disability has begun to progress, and I began noticing cognitive challenges as well. My neurologist was dismissive of them, as “no new lesions” were apparent on MRIs, though previous damage is apparent in MRIs.

    When I finally got the neurologist to take my concerns seriously, I was given standard dementia screening tests AND an IQ test (couldn’t figure out why an IQ test, but what do I know?). I’m a former nuclear engineer, so guess what? My IQ is very high. Therefore, in the neurologist’s eyes, I was fine.

    But I kept demanding other testing because I’m struggling to keep up with work responsibilities. Concentrating is often impossible, solving problems very difficult, beginning to separate from friends and family, becoming depressed, etc…

    Finally, after intense neurocognitive testing, the diagnosis returned. “Neurocognitive disorder due to multiple sclerosis, unspecified anxiety disorder (including phobic/reactive distress component) and unspecified adjustment disorder with depressed mood.”

    I guess my point is this: get on a DMT as soon as possible when diagnosed. Take control of your care. What Prof G is saying here is real.

  • No sugar coating. Not to patients and most certainly not to HCP and payors.

    We need the big guns deployed early and widely, sugar coating in any direction works directly against this.

  • Which DMTs have been proven to prevent the preventable dementia?
    I’m on Natalizumab, do I need to change?

    Also, since the effective DMTs haven’t been out for so long, is it even possible to say right now which are most effective in stopping the dementia?

  • To be honest, I think people with MS are well aware that ‘time is brain’ and that, if anything, it’s a certain subset of health professionals that need to be told this. My MS symptoms became obvious in 2018, but it took over a year to finally convince my GP to refer me (privately!) for an MRI. Even when that showed demyelination, it then took a very long time to have a lumbar puncture to confirm diagnosis, and then further delays have meant I only just started treatment in 2021.

    I was shocked at the dissonance between ‘early treatment is important’ and the fact I kept being given appointments over six months in the future even after my neurologist had acknowledged it almost certainly was MS. I waited so long for my lumbar puncture that the MRI I had the same day was unequivocal enough to mean that I wouldn’t have even needed the LP. Annoying and distressing.

  • PwMS are prone to Swiss cheese like black holes in grey matter and associated dementia….That’s a not so so gouda. Takeaway is take your DMTs and prevent end organ damage.

By Prof G



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