Old age; how is it going to affect me?

Is ageing a disease? It is if you have MS.

We have been making the argument for moving our treatment target in MS to focus on old age; i.e. how do we your HCPs get you to old age with enough brain to deal with the ravages of age-related cognitive impairment?

Mechanisms of neuronal loss in MS

It is clear that your brain and cognitive reserves are what protects you from the ‘normal age-related neuronal drop-out’, which occurs as part of normal life. We know that MS shreds both brain (size) and cognitive (synapses) reserve and hence it should bring forward age-related cognitive impairment in MSers. The latter was a hypothesis, but the study below shows it is not necessarily a hypothesis anymore. In summary, older MSers are more likely to be cognitively impaired (77%) compared to younger MSers (43%). The challenge is to prevent this. How? Early effective treatment to stop the shredder and to make sure we tackle smouldering MS.

Do you need any more evidence? Please ask your neurologist if you have NEDA is there any evidence of smouldering MS? He/She may want to know what smouldering MS is. You can then tell them it is what is happening at the bottom of the treatment pyramid that is out of sight of our routine monitoring. This is the reason why you need to self-monitor and if you are getting worse you need to ask what can be done about it.

Treatment targets in MS

Branco et al. Aging with multiple sclerosis: prevalence and profile of cognitive impairment. Neurol Sci. 2019 Apr 23. doi: 10.1007/s10072-019-03875-7.

BACKGROUND: The increase in life expectancy of patients with multiple sclerosis (MS) requires a better knowledge of disease features in the older patients group.

OBJECTIVE: To describe the prevalence and profile of cognitive impairment (CI) in older patients with MS and perform a comparison with younger patients.

METHODS: Patients were consecutively recruited for 6 months. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop Test. CI was defined as impairment in ≥ 2 cognitive domains.

RESULTS: We identified 111 patients older than 55 years (mean age 59.7 years). The prevalence of CI was 77.4%, which was significantly higher than in younger patients (42.8%; p < 0.01). Information processing speed was the most impaired domain (68.8%), followed by verbal learning (49.5%), executive function (47.7%), and visuospatial learning (26.6%). We found no significant differences in the prevalence of impairment in the distinct cognitive domains between older and younger patients with CI. Depression and fatigue were not associated with increased CI among patients in the older age group (p > 0.70).

CONCLUSION: There is a remarkably high frequency of CI in older patients with MS. The similar profile of CI between older and younger patients suggests that CI is mostly directly related to MS itself and not to comorbid age-related disorders.

CoI: multiple

35 thoughts on “Old age; how is it going to affect me?”

  1. If you have SPMS turn the answer to “ what can be done about it’ is zilch . It really does annoy me all this unicorn stuff., take more exercise is another one !,

    1. Tessa not true. We now know that SPMS is modifiable, but we need more than just an anti-inflammatory therapy. We need add-on neuroprotectives, remyelination and neurorestorative therapies and then we need to target anti-ageing mechanisms. At the moment that is living a brain healthy life and focusing on all eliminating all the small things that speed-up disease worsening, e.g. comorbidities, infections, poor sleep, anticholinergics, etc. and enhancing the things that may slow down worsening, e.g. exercise, diet, social capital, etc.

      I disagree with you; there is a lot that can be done if you have SPMS. This is why I am pushing the theory of marginal gains for treating MS.

      1. “We need add-on neuroprotectives, remyelination and neurorestorative therapies”

        Prof G,

        I’ve heard this since the 1990s, but nothing is yet available. What happened to Biogen’s anti-lingo antibody which was to promote remyelination? What looks promising in the pipeline? Will any big announcements be made at the AAN which I’m sure you’ll be attending? I preferred MS in the 1990s when it was an autoimmune disease affecting the white matter. Now it’s a neurodegenerative, dementing, whole brain disease!

      2. Is it right to give Rituxan to patient when the disease is not so active anymore?
        Anders Svenningsson:
        I would say it is a matter of age. Around 55-60 (maybe youger!) the combination of a prolonged treatment effect and natural cessation of disease activity makes treatment of very low value, but you still retain the risks. So I would say as a rule of thumb that if you are over 50 and have had a not so active disease anytime it might be worth trying discontinuing all therapies. Of course keep yearly MRI controls.

      3. This advice is based on a leg/EDSS-view of MS and not an arm-, swallowing/speech- or cognitive-view of MS. Why should you right off someone’s cognition, etc. to MS because they are old if you can slow down the loss of function in systems with preserved reserve capacity? Your call. This is why we are doing the ORATORIO-HAND and CHARIOT-MS trials; to change opinion and to help pwMS who happen to be older and/or with more advanced disease.

      4. I actually disagree with both Svenningsson and you. I don’t believe in axonopathy theory. It is microglia derived neurodegeneration that mostly affects neuroplasticity and “pronounces” the damage from demyelination axons. Antiinflammatories would offer very little. Mainstream MS theory looks obsolete to me. I am only positive because microglia seem to be the answer to many neurological diseases, so the solution will probably not come from MSologists. Till then, SPMS cannot be regarded treatable.

      5. SPMS is not modifiable currently other than what the normal aging population should in terms of preventative measures as one ages anyways.

        The immunosuppressant agents are 100% not the answer for “non-active” MS. At best they will slightly delay progression to same miserable endpoint with the only person noticing this being a statistician.

        There are no neuroprotective agents, no remyelination and no neurorestoration products because of the sheer and utter greed of Pharma and its paid associates over the last 1/4 century. There will be nothing available at the pharmacy anywhere on the horizon to complete your treatment pyramid.

        Your theory of marginal gains applies to all aging individuals, not only MS patients.

      6. Watch this space; we know things you don’t know. SPMS is definitely modifiable. Don’t forget MS is #1_not_2_or_3_diseases.

      7. Watch this space; we know things you don’t know.
        People have been for the last decade…
        and now for the next decade…
        still no EBV therapy/vaccine

      8. “We need add-on neuroprotectives, remyelination and neurorestorative therapies and then we need to target anti-ageing mechanisms. ”

        In other words we need the year 2050 or better yet 2150

  2. Why not include age-matched older and younger healthy control groups in the study? Seems to me that only half the study was done. Wouldn’t it be better to be able to make a stronger conclusion than “the similar profile of CI between older & younger patients suggests that CI is mostly directly related to MS itself”?

  3. I’m looking at two bottom layers of your pyramid “Treatments targets in MS”. If I’m interpreting this right, you’re saying that OCBs in CSF are better (more accurate? robust?) markers of smouldering MS than NfLs in CSF?

    1. No. There is evidence that the OCBs may be pathogenic in MS and if that is the case we need to scrub the CNS clean of B-cells and plasma cells. This is our next study or panel of studies we are focusing on.

      1. You know better than me that the role of autoantibodies is ms uncertain

        Why are you so focus on this?

        Do you think all plama cell are made equal?


  4. I guess a lower threshold for offering patients HSCT might help MSers from not going daft at too high a rate??

    Maybe American bone marrow transplanters have set out in the right direction by saying HSCT should be considered “standard of care” (I wish they would recommend lowering the threshold for treatment though):

    Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation

    Jeffrey A. Cohen, Laura E. Baldassari, Harold L. Atkins, James D. Bowen, Christopher Bredeson, Paul A. Carpenter, John R. Corboy, Mark S. Freedman, Linda M. Griffith, Robert Lowsky, Navneet S. Majhail, Paolo A. Muraro1, Richard A. Nash, Marcelo C. Pasquini, Stefanie Sarantopoulos, Bipin N. Savani, Jan Storek, Keith M. Sullivan, George E. Georges

    A B S T R A C T
    Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, demyelinating and degenerative disease of the central nervous system. Approved disease-modifying therapies may be incompletely effective in some patients with highly active relapsing disease and high risk of disability. The use of immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated in retrospective studies, clinical trials, and meta-analyses/systematic reviews as an approach to address this unmet clinical need. On behalf of the American Society for Blood and Bone Marrow Transplantation (ASBMT), a panel of experts in AHCT and MS convened to review available evidence and make recommendations on MS as an indication for AHCT. A review of recent literature identified 8 retrospective studies, 8 clinical trials, and 3 meta-analyses/systematic reviews. In aggregate, these studies indicate that AHCT is an efficacious and safe treatment for active relapsing forms of MS to prevent clinical relapse, magnetic resonance imaging-detectable lesion activity, and worsening disability and to reverse disability without unexpected adverse events. Based on the available evidence, the ASBMT recommends that treatment-refractory relapsing MS with high risk of future disability be considered a “standard of care, clinical evidence available” indication for AHCT. Collaboration of neurologists with expertise in treating MS and transplantation physicians with experience performing AHCT for autoimmune disease is crucial for ensuring appropriate patient selection and optimizing transplantation procedures to improve patient outcomes. Transplantation centers in the United States and Canada are strongly encouraged to report baseline and outcomes data on patients receiving AHCT for multiple sclerosis to the Center for International Blood and Marrow Transplant Research.

    1. You may have noticed that I have moved my position on this. I call it reframing the debate on DMTs and I agree that HSCT should become first-line.

      1. Not long ago I was diagnosed with RRMS. Hence, I have decided to spend my summer holiday as an HSCT tourist. I admit that I am scared shitless (pardon my French), and very afraid of catching a flue caused by for instance a multi-drug resistant Klebsiella pneumoniae 🙁 . I profoundly wish that I could have received the treatment here at home in safe surroundings; alas, our (Norwegian) neurologists and hematologist have shoot themselves in the foot. They live in denial, and demand more trials (HSCT against alemtuzumab) before they may exit their belief system and offer HSCT first-line – I will probably be dead by then. Anyway, their trials (HSCT against alemtuzumab) may now be hampered as The European Medicines Agency has started a review of alemtuzumab – the neurologist’s favorite – following recent reports of side effects affecting the heart, blood vessels, liver and immune system. The most efficacious MS treatments are all nasty – both the monoclonal antibodies and HSCT. As stated in the article above, HSCT is not an experiment, and we with MS should, thus, be allowed to make an informed decision, where HSCT is an option. Neurologists and hematologists should now take their blindfolds off, and recognize that MSers make these informed decisions already, without their expert advice, alas, being forced to spend their own savings abroad. Personally, I can not hang out at the hospital until my health care professionals have surgery to get bullets removed from their feet. I am in a hurry; my loved ones notice, and sometimes tell me, that my cognition is on a slippery slope to ruin.

      2. I simply love your line ‘Neurologists and haematologists should now take their blindfolds off and recognize that MSers make these informed decisions already, without their expert advice’; I will quote you in a talk the next time I get the opportunity to.

      3. Thank you Gavin! I am sure that it warms the hearts of all MSers that you stand on the baracade and wave a flag for us. You new perspectives on the biology, pathogenesis and strategies for treatment are of essential value. I read your posts with great interest. By the way, I am 55 and my RRMS is being treated with rituximab, but my brain is clearly still smoldering. That I need to work on, thus HSCT. Alas, my HCPs think I am a naughty boy 🙂

  5. Re: “Please ask your neurologist if you have NEDA is there any evidence of smouldering MS? He/She may want to know what smouldering MS is. ”

    You then ask the patient to be vigilant about their MS in regard to worsening and what can be done about it.

    My question is: If the neuro does not even know what shouldering MS is then how would they go about with a treatment plan?

    1. #ThinkSmouldering is about getting the community to beyond NEDA and focus on optimising #BrainHealth and getting add-on therapies through the pipeline. Like everything in life it takes time, and foot soldiers, to move a field forward. Thank you for reading the post, it is much appreciated.

  6. Gavin last year you very kindly asked MSbase to crunch the numbers for the study concluding that DMTs show no efficacy for those age 53+
    Where does it sit in regards to your position on the ways to most effectively manage ageing in PwMS?
    Any updates yet from MSbase?

    It’s those left to pick up the pieces that hurts me, as the 55yr old mother of an only child.
    Knowing that one in every two of us will develop Alzheimer’s, he will roll his eyes saying: ‘Don’t you get dementia too Dad, I’ll have enough looking after Mum!’ Said in jest, but reflecting an underlying anxiety! So whilst I’ve left off learning to play an instrument, or a new language, I’m working at maintaining brain health.

    1. MSBase are on the case and the data will emerge in time; possibly at next ECTRIMS. But you need to realise they are also hampered by using the EDSS.

  7. I had undiagnosed MS since the age of 15. I am 55 now. My MS was finally diagnosed when I was 43. I was diagnosed with Mild Cognitive Impairment (NeuroPsych Eval) a few months after my MS diagnosis, but I had been experiencing cognitive issues for 6 years prior to the Mild Cognitive Impairment diagnosis.

    I have brain atrophy that increases slightly, every year. The atrophy includes enlargening of the ventricles and diffuse volume lose of the cerebrum and cerebellum. This year, Whole brain Volume declined 3% from the prior year brain MRI, as detected by Neuroquant. I carry a heavy white matter lesion burden – more than 30 brain lesions present at time of diagnosis. This has remained relatively stable. At present, I have over 6 black hole brain lesions on the T1 MRI. I relapse or develop a new lesion approximately 1x every 6 years. I have 5 lesions plus cord atrophy, mainly in my T-Spine.

    I have not been on any DMTs, since a brief clinical trial of Copaxone (serious side effects) in 2007. Because it took more than 27 years to diagnose me with MS, I never had the opportunity to hit it hard and early with any kind of treatment. I understand Lemtrada showed some protective effect against brain atrophy but that drug is too dangerous to consider for now.

    I tried 1200 MG Alpha Lipoic Acid, which was shown in a study by Oregon Health Sciences University, to reduce the rate of brain atrophy. I could not tolerate the ALA. I am on Biotin now, but uncertain that it has any protective effect against brain atrophy. At this stage of the game, do I even have any options?

      1. I am not sure what my EDSS is. My MS Neurologist never tests this. From what I have seem of the EDSS criteria, I would be about a 4.5/5.

  8. I rest my case ! It seems to be physio/ cognitive therapy / exercise ( difficult with increasing disability) and medication for related issues .according to the MS Trust. Not quite the holy grail

    1. I’d like to recommend Trevor Wicken MS Gym on YouTube. He offers a range of exercises whilst seated as well as for the less disabled PwMS. Also I know I’m not the only one who finds his presentation easy to follow and entertaining – makes you smile, if not laugh!
      Should also point out perhaps that I was diagnosed late at age 52yrs and have received Lemtrada. Despite the study conclusion that I’ve mentioned in my earlier reply, I’ve been NEDA since last summer and I’ve also found that my exercising at the gym, or on a chair at home when fatigued, has improved. However even before completing the Lemtrada I was able to get rid of the foot drop and the walking stick as a result of daily exercises. From my personal experience I’d recommend to anyone the benefit of DMTs if eligible for them, and the benefits of exercise and diet and I hope that others are finding they’re benefitting as I have!

  9. You said manny times that age its a neurodegenerative disease

    This study its a bit flawed

    The old ms group should be paired with contropl age matched to account for CI

    And the younger ms patient group also with age control non ms

    The older patients had significantly
    lower education and a higher EDSS when compared with
    the younger patient group (p < 0.01). The distribution of disease
    subtypes was different between the groups, with increased
    frequency of progressive forms in the older patient
    group (p < 0.01).

    For the purpose of this study, we selected
    the patients with 55 years or older, and compared
    them with the rest of the sample. This age cut-off was
    chosen considering it is when disorders affecting cognitive
    function start to become relevant and where epidemiological
    data on the prevalence of mild cognitive impairment
    (MCI) and dementia starts to become available [19, 20].

    Also some older ms could have CI overlap with other etiology

    They did not look for those biomarker , so underpower study

    The differences in neuropsychological profile are useful to
    guide the differential diagnosis of CI in older patients with
    MS, although we cannot completely exclude an overlap between
    MS-related CI and degenerative dementia. It can also
    be challenging to differentiate CI secondary to MS from the
    one due to vascular dementia (VaD), which is very common in
    the elderly [26]. Cerebral small-vessel disease, most often
    associated with CI [27] in VaD, is characterized by lacunes
    and widespread ischemic white matter disease, which can resemble
    the white matter lesions seen in MS [28] and may
    contribute to cognitive decline by affecting information processing
    speed and executive functions [29]. Therefore, for the
    differential diagnosis, other clinical, laboratory, and imaging
    data are mandatory. This is particularly relevant taking into
    account that the incidence of vascular comorbidities such as
    diabetes, hypertension, and hyperlipidemia is rising within the
    MS population [30]. Biomarkers such as CSF tau and β-
    amyloid can also be important, as they would help to rule

    out neurodegenerative dementia. One limitation of the present
    study is indeed the lack of assessment of the above factors.


  10. How will old age affect me with my slow early onset PPMS? It will kill me eventually. Death and taxes…
    I’d hope for a real and tolerable treatment offering more than possible delay of symptoms + hefty side effect and/or infection risk + endless monitoring and clinic visits. But I’m not sure there will be one in time for me. So I make the best of my days and do all I can for myself! Diet, being active.

  11. I turned 78 on 4/23. I don’t feel I have as much CI as many MSers. The primary reason for this is my resumption of playing the violin after I was forced by MS to retire at age 60 from teaching academically advanced full time gifted elementary students. Finding a teacher who was actually interested in teaching me was difficult initially. I will never return to my former level of proficiency but I am continuing to advance with the help of a very gifted teacher. Initially I was playing in a string ensemble at a local community college. The first semester I was in the last seat of the second violins. After that, I was concert master until the program was dropped. After that, encouraged by my teacher at the time, a began playing with the Houston Sinfonietta, a community orchestra founded in 1979. I’ve just completed my 10th year with them. Our last concert include Vivaldi’s Four Seasons and Dvorak’s 5th Symphony. Not too shabby for someone who had not played for almost 40 years. Three years ago I had the opportunity to study and performace chamber music under the tutelage of the Princeton Quartet for 8 days in Denver. This was the first time I had played serious chamber music in close to 50 years. The skills needed to perform solo pieces, orchestral works, and chamber music are uniquely different. For the last three summers, quantum gains have been made. Perhaps the most important skill has been the knowledge gained from studying the score of various compositions. I now also purchase the scores of all symphonies and major works the Sinfonietta performs. The has greatly improved my performances. I have also taught myself how to play the viola which involves learning a different staff. I teach violin and viola employing neuropsychologically principles of learning as well as perform at my church. My neurologist has noted that my corpus callosum has grown larger. The radiologist who has interpreted my MRI’s for a number of years also noted changes. My brain shrinkage is less than one my age without MS.

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