Sunday, 11 May 2014

Saving Brain: cognitive decline in MSers 18-year follow-up

Saving Brain: is it time to shift our treatment goals in MS? #MSBlog #MSResearch

"It is about a year since I started the campaign to rebrand MS as a dementia; i.e. a preventable dementia. The reason for doing this was to make people, in particular the regulators and payers, about the hidden burden of this disease and shift the focus to preventing progressive cognitive impairment in MS. I think this campaign has been successful because it has generated debate, which is what I wanted it to do, and it coincided with the beginning of a shift in the way regulators are thinking about MS. For example, it is very reassuring to have a very effective DMT available as a first-line agent for those MSers with active disease who want maximum disease control early on the course of the disease. A year ago this position was unimaginable in Europe."

"The main concern that has arisen with rebranding MS a dementia is that the community thinks it will be stigmatizing. I agree with them, but I still think we need to keep cognitive impairment high-up on the MS agenda. Cognitive impairment is the main reason why MSers have difficulty keeping their jobs earlier in the disease and it is the main driver of mental fatigue. The following study is small, but illustrates the problem of cognitive impairment in MSers. At the start of interferon-beta-1a (Avonex) therapy only 41% of MSers were cognitively impaired. However, after 18 years of follow-up on treatment that number increased to 59%. I wonder how much higher than 59% it would have been without interferon-beta-1a treatment? Interferon-beta-1a has been shown, albeit is a small sub-study, to delay the progression of cognitive impairment in MS. Data has recently emerged that cognitive impairment correlates with brain atrophy or brain volume loss. It would have been nice to see this included in this study."

"This study demonstrates how important it is for us to be focusing on Saving Brain and preventing progressive cognitive impairment in MS. To do  this we need to refocus our treatment goals to include cognitive impairment. Why wouldn't we?"


Brains are beautiful!

Strober LB et al. Cognitive impairment in multiple sclerosis: An 18 year follow-up study. MSARDS epub

Background: Cognitive impairment occurs in 40–65% of MSers. Less is known about the rate and pattern of cognitive decline over the course of the illness.

Objective: To examine long-term changes in cognition among patients enrolled in the phase III clinical trial of intramuscular interferon beta-1a (IM IFN╬▓-1a).

Methods: Twenty-two MSers underwent a longitudinal investigation comparing neuropsychological test performance at study entry and 18-year follow-up.

Results: Over the 18 year interval, significant declines were observed on measures of information processing speed, simple and complex auditory attention, episodic learning and memory, and visual construction. Nine MSers (41%) were found to be cognitively impaired at study entry. At follow-up 13 MSers (59%) were cognitively impaired. While both the impaired and unimpaired patients at baseline experienced declines on these measures, only one measure, the Symbol Digit Modalities Test (SDMT), demonstrated a group (cognitively impaired versus intact at baseline)×time interaction. This interaction was characterized by a steeper decline in the unimpaired than the impaired group at baseline.

Conclusions: Over an 18 year period, our results suggest that cognitive impairment in MS progresses, with declines being most evident on measures known to be most sensitive to MS-related cognitive difficulties both cross-sectionally and longitudinally.

CoI: multiple

13 comments:

  1. While I understand the reasons for you seeking to rebrand MS as a dementia, most of us are diagnosed in our 20s and 30s. We will have elderly relatives with dementia. To add dementia to the huge list of horrible symptoms we have to deal with would be the straw that broke the camel's back (for me at least). I be grateful for a guestimate of when neuroprotective agents might be available.

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    1. Try to learn new languanges to slow off the decline - that's what I have been doing for a long time and it works.

      I believe MS will always differ from 'real' dementia - the docs just need to re-brand it in order to get more attention = funding for treatments. If MS stays classified as a 'niche' disease the progress will be much slower to come by.

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  2. Re: "I be grateful for a guestimate of when neuroprotective agents might be available."

    In reality all anti-inflammatory DMTs are neuroprotective. Simply by reducing inflammation you protect the brain and spinal cord from damage, The more potent the anti-inflammatory the greater the neuroprotection; at present natalizumab and alemtuzumab have the greatest impact on "Saving Brain".

    Down stream of inflammatory events is another story; laquinimod is the drug that looks the most promising in late stage development. However, its greatest promise lies in it being used in combination and we are many years of combination therapies.

    Another promising agent is Simvastatin. The phase 2 trial was positive. Now all wee need is a phase three programme to show it really works. Who is going to do these studies?

    Please see my earlier post on this issue: http://multiple-sclerosis-research.blogspot.co.uk/2014/03/politics-lessons-from-simvastatin-trial.html

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    1. In short: this weekend has demonstrated to us MSers that our prospects remain bleak regardless of whatever brand of multiple sclerosis we fall into. We are being sold nothing concrete. MS remains beyond understanding.

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    2. I think it is virtually a given that RRMS will transition to SPMS without any intervention in the majority of patients. To me (and most researchers) there is no difference between SPMS and PPMS. There has really been no big revelation, you have just not been paying attention.

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  3. Prof G,

    If the Charcot project ends with a positive outcome, will the drug being trialled have a neuroprotective effect i.e. By controlling ebv / hervs could it be protecting brain?

    Thanks

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  4. Cognitive impairment would be a good data point to have during a clinical trial if it could be measured in a standardized repeatable test. The only problem I could see with this suggestion is that people have different levels of "cognitive reserve" and it would be a difficult parameter to measure.

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  5. It's disheartening that Simvastatin 80mg isn't available; any ideas when/if/how this would become available? Thanks as ever...

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    1. It is available in 10 to 80 mg tablets/capsules. But it could cause myopathy in such a dose, which would be very bad addition to MS, isn't it?
      (I'm not a doctor).

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    2. There was no does response undertaken and who's to say that a lower dose would not be the same. The data was from a phase II study they need a phase III study and generally a dose relationship would be needed by the regulators to approve the dug. Who is going to fund this. This again speaks to the question should phase II be done if there is no real plan and highway to get the drug to people

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  6. Mouse Doc - do you know if there are any dangers with taking simvastatin and tecfidera together? I'd like to start simva (low dosage first) for my arteries and tecfidera for MS.

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    1. All drugs have dangers.... you need to discuss drug combinations with your neuro,

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  7. And to seek "inside" the cognitive disability of MS, I suggest you see Gingold's book.

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