Barts-MS rose-tinted-odometer: ★
As someone with MS do you worry about how you are going to cope with ageing and old age?
As MS shreds both your brain and cognitive reserve will MS bring forward and accelerate the ageing process and the time when you may develop neurodegenerative diseases such as Alzheimer’s disease? These are all hypotheses but are very relevant to people with MS (pwMS) and their families.
I recall how much stick I got from the MS community, including some very close colleagues when I tried to rebrand MS as a ‘preventable dementia’. The objective of the #ThinkCognition campaign was to make the MS community look beyond the blinkers of the EDSS and realise that MS was not only physical disabling but it was affecting cognition much earlier than people realised. For example, 40% of people already have significant cognitive impairment in at least two cognitive domains at the CIS (clinically-isolated syndrome) stage of their disease. If you go earlier to RIS (radiologically-isolated syndrome) or asymptomatic stage of the disease about a quarter of subjects have cognitive impairment. People with RIS and CIS are not aware of having cognitive impairment because the brain is able to compensate for the damage at an early stage.
In early MS cognitive impairment is more likely to cause cognitive fatigue and be associated with anxiety and depression than overt cognitive problems. The brain compensates for the damage by doing extra work, consuming more energy and getting tired more easily. Most people with MS realise they attention spans are often markedly reduced because of this phenomenon.
The reason why 50% of pwMS living in Europe are unemployed at an EDSS of 3.0 to 3.5 is not physical but cognitive disabilities. The #ThinkCognition campaign highlights the early hit the MS brain takes and makes the argument for effective early treatment to prevent dementia.
The problem with society’s view of dementia, i.e. of a little old lady with poor memory in a care home, is that it doesn’t easily translate to MS. What you have to remember is that dementia is a syndrome and MS is a well-known cause of dementia. The definition of dementia is that it is an acquired (not born with it), chronic (greater than 6 months), progressive condition (gets worse over time) that affects cognition in multiple domains (for example, problem-solving, processing speed, memory, speech, calculations, etc.) and impacts on the individuals occupational and social functioning. I would challenge anyone to say that worsening MS-related cognitive impairment fulfil this definition of dementia. The good news is that dementia associated with MS is preventable, i.e. if you treat MS early and effectively you will stop the end-organ damage and prevent the consequences of MS on longterm cognitive functioning.
Now the question about bringing forward ageing and the presentation of other neurodegenerative diseases is an open question. Below is a case report of an elderly woman with MS who presents with memory loss and a workup showed a pattern of cognitive decline that was more in keeping with Alzheimer’s disease than MS. She then goes onto to have diagnostic amyloid and is diagnosed as having Alzheimer’s disease. One could argue if she didn’t have MS this may have protected her from getting Alzheimer’s disease or at least delayed its onset by several years.
It is important to stress that the type of cognitive impairment associated with MS is very different to that of classic or amnestic Alzheimer’s disease and well-done neuropsychological tests should be able to differentiate the two conditions (see pilot study below). Saying that I have a handful of patients with ‘cognitive MS’ who have taken a massive hit on their ability to store and process short term memory because in their case MS has affected the temporal lobes and their connecting structures that are critical for memory.
Other issues that the #ThinkCognition campaign addresses are (1) the need to be able to identify relapses as being purely cognitive, (2) using cognitive impairment to say that patients with RIS have CIS or MS so they can be treated, (3) using a change in cognition to define worsening MS or progressive disease, (4) incorporating cognition into our treatment target in MS, (5) including cognitive screening or testing as part of the annual MS assessment and (6) including cognition in our longterm treatment goal of maximising brain health for the life of the pwMS.
I want to point out that none of the points I make in this post is necessarily accepted by the wider MS community and many of the points remain controversial, which is why I would encourage a debate around these issues. What I can tell you, however, if I had MS I would want my neurologist and MS team to treat me as if my brain was the most precious thing on planet earth; I would want them to protect my cognition and make it their number one objective. I suspect this is easier said than done.
Jakimovski et al. Differential Diagnosis of Cognitive Decline in Elderly Individuals With Multiple Sclerosis. Cogn Behav Neurol. 2020 Dec;33(4):294-300.
Due to increasingly improved disability outcomes, and the resultant significantly improved life span, of the multiple sclerosis (MS) population, questions regarding cognitive aging and the prevalence of comorbid Alzheimer disease (AD) have emerged. We describe neuropsychological and MRI-based changes that occurred in an 84-year-old MS patient with comorbid amnestic mild cognitive impairment (a precursor to AD) and cerebrovascular pathology. The neuropsychological examination demonstrated impairment in cognitive processing speed as well as in verbal and visual memory-domains that are potentially affected by any, or all, of the three co-existing diseases. Amyloid-based PET imaging showed increased focal uptake within the gray matter of the occipital lobe. We highlight how these clinical and radiologic observations can inform future research that could elucidate interactions between MS, a probable AD diagnosis, and cerebrovascular pathology in elderly individuals with MS. A comprehensive neuropsychological examination of multiple cognitive domains of individuals with MS may aid in the differential diagnosis of late-in-life cognitive decline.
Roy et al. Preliminary investigation of cognitive function in aged multiple sclerosis patients: Challenges in detecting comorbid Alzheimer’s disease. Mult Scler Relat Disord. 2018 May;22:52-56.
Background: Cognitive impairment can be seen in patients of all ages with multiple sclerosis (MS). However, there is limited research on neurocognitive disorder in older adults with MS and how to detect Alzheimer’s disease (AD) or its prodromal stage, amnestic mild cognitive impairment (aMCI). Thus, the MS clinician is challenged to discriminate between signs of MS-related cognitive decline versus a secondary neurodegenerative process.
Objective: Compare cognition in older MS patients to patients with AD and aMCI.
Methods: We evaluated cognitively impaired and unimpaired MS patients, AD patients, aMCI patients, and healthy controls (HCs), all elderly (n = 20 per group). AD and aMCI diagnoses were derived by consensus conference independent of the MS research project. Neuropsychological measures assessed domains commonly affected in AD, including verbal memory and expressive language.
Results: Cognitively impaired and unimpaired MS groups did not differ on any measures sensitive to AD. Unimpaired MS patients were comparable to HCs. Impaired MS patients showed decreased semantic fluency, similar to aMCI patients. Lastly, while both AD and aMCI groups had deficient memory retention, there was no evidence of a retention deficit in either MS group.
Conclusion: Our findings suggest that the cognitive profiles of MS and AD are distinct. In contrast to AD, MS is not associated with impairment of memory consolidation. However, there may be overlap between cognitive deficits related to MS and aMCI. Thus, evidence of poor memory retention, in an older MS patient may merit comprehensive dementia evaluation. The study is preliminary and includes no AD biomarkers (e.g., amyloid imaging) to confirm or rule out AD pathology.
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CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
This, a million times this, and not just in older patients. I’m very blessed to have inherited my father’s towering intellectual capacity – because when MS hit there was more redundant capacity. I’m now 20 years in from my first episode and maybe 25 years since I first started to notice a decline, when I was 19. I can definitely feel the difference MS has made.
For reference when he was my age, 44, my father was part of the team helping to create the system now used worldwide for classifying pharmaceutical adverse reactions.
Whereas, as a web developer (not even a proper software engineer), I’m struggling to learn new programming languages. And as an emigrant I’m struggling to learn the local language despite being immersed in it for 10 years. My concentration is shot. My problems solving abilities are practically non-existent.
The only relief I had from this decline was a 2 year gap when I was taking Tecfidera which seemed to somehow reverse the decline. But other complications meant I was withdrawn from the treatment. I’ve been on ocrelizumab for the last year and am less than impressed with the results.
ProfG – solely from my experience, I believe you are truly on to something with this approach.
For me personally, this is the scariest thing about my MS. Are there any specific medications proven to stop cognitive decline like there are for relapses?
Which of the high efficacy drugs are more likely to keep cognitive decline to a minimum?
The DMTs that protect the end-organ the most; at the top of the pile are HSCT & Alemtuzumab, then natalizumab and the also-rans after that. However, brain volume loss is also about when you treat; if you start early the greater the impact. Once your brain has acquired too much damage and smouldering MS is well-established even alemtuzumab/HSCT are not good enough.
Anyway of the patient knowing when MS becomes well-established?
Ths is why we need combination therapies in MS; to go beyond simply suppressing focal inflammation but to target the processes that drive smouldering MS.
Your words from 17 January 2014 on this blog:
“I strongly believe in a combination therapy strategy, i.e. an anti-inflammatory drug in combination with a neuroprotective therapy and early treatment.”
Nearly six years later, are we any closer to effective combination therapies? What is holding up progress given that we know what the problem is (smouldering MS) and what the solution is (combination therapies)?
Can someone wake me up when these combination therapies become available.
Not for the want of research at our end Sidney. Lack of interest from pharma is primary block as they prefer to concentrate on their disease modifiers plus curious selection of agents for the MS Smart 1 & 2 trials etc etc etc.
Hugely frustrating not only for you but also for those who have thrown their heart and souls, not to mention sacrificing their weekends/holidays for many years to get essentially nowhere.
MD2,
I’ve never doubted the effort, but there’s a Groundhog Day feeling creeping in. Unfortunately effort doesn’t stop smouldering MS. Have a good weekend.
I know, I wish we were much further on. I feel a deep personal sense of profound failure to be honest.
You have a good weekend too.
You’ve nothing to feel defensive about..it’s a tough field..no progress/no results is the norm..CA started regenerative medicine tax
funded plan.. 8.5 Billion has been spent w/very little to no results/licensed therapies.
https://en.wikipedia.org/wiki/California_Institute_for_Regenerative_Medicine
Not for lack of trying. Sometimes it takes time to move treatment concepts forward. But it is happening and Pharma are taking tentative steps. Science is no different to other fields and follows an adoption curve, which is often slow.
It’s sad to find out that pharma are running the show and dictating the pace of change. Any guesstimate as to when we might see effective combination treatments available – 5, 10 years… it a difficult position for MSers being told that time is brain / the shredder never stops, but that pharma who run the show / neuros who treat patients are happy to dawdle along at a snails pace (actually that’s an insult to the speed of snails). Have a restful weekend.
We have done PROXIMUS combinating trial. However trials dont gow on trees, have spent the past three years saying combinations you have to ask people including your mates why monotherapies are still on the table
As someone with MS do you worry about how you are going to cope with ageing and old age?
No. Because I am already doing everything I can for my health, I’m doing pretty well, and there’s no point worrying about the future.
Prof, i am truly impressed by your commitment to this blog when you should still have your feet up. However, you posted yesterday about hope and depression…..these articles, whilst necessary and informative, only lead to the latter. Its Friday – lift our spirits by telling us of all the new wonderful drugs that are on the horizon. or how the lessons learnt through covid could have a positive influence on the speed and focus of MS research (caused apparently by another virus). Sorry, i dont like to be critical as you take a lot of flak for putting your head above the parapet and you’re an absolute champ for the MS community but sometimes i dont want to hear again about MS shredding my brain. I know we dont have to read on but it is quite addictive! like prodding a bruise to see how much it hurts
Sometimes you have to be cruel to be kind. Please note the rose-tinted-odometer score, which I added to my posts at the request of another reader who didn’t want to read depressing posts 😉 I did buy myself a pair of rose-tinted glasses, which I loved, by I have misplaced them or lost them and can’t find them anywhere.
Ah ok….this explains it. Dont let the loss of your glasses put you off writing rose tinted posts though. I will send a new pair to Barts if it means that we will receive more of them 🙂
Re:“Sometimes you have to be cruel to be kind”
Prof G and Nick Lowe. After your recovery I see a duet in the making.
🎵“You still mystify (MS) and I wanna know why….”🎵😊
YYEEESSSSSSSS !!!!
I wholeheartedly agree with your thought process and analysis related to cognition and MS.
I was diagnosed in Dec 2011 and relapsed on average 3 debilitating relapses of varying intensity every year since. I was on avonex and continued to relapse , coming off DMT to start a family and was advised to finish family first (never informed that some DMT are possible for child bearing and feeding , but that’s another topic entirely). I relapsed aggressively (High debilitating every 6 weeks on average ) after my second child was born. Although in hindsight I started very apparent Cognition depletion in 2016. I worked in high stress , high CPU usage fast paced job and could no longer think correctly. I finally got on tysabri a year after my son was born and started to see improvement . I then had HSCT and the primary reason was cognition and to endeavour to stop the brain depletion while I potentially still had the reserves ( 39 years) . I am one year post transplant in London and am very much of the opinion that high efficacy treatments being offered earlier in the course of the disease is paramount . I was not offered any despite a lot of relapse, because I was too much of a “walk it off “ person ,even when i couldn’t walk or blind 😊.
I spoke at length with the NHS team and they unfortunately either do not have resources or do not appreciate that the cognition decline in MS persons is something that should and can be monitored .
Also I think that HCP should have training to speak to patients to assist them in identifying their reducing CPU. This has to involve the patient as the current testing may not be enough. As an example I went to a neuropsychological assessment and in the end I was told I was above average for my age and education , I assure you I was not myself and this brought on crippling depression . One cannot deal with legs not working unless one has the brain capacity to process that disability . HCP need absolutely to work on how brain health assessments can be done , in conjunction with patients, being aware that patients may not be able to identify and may just say “I’m fine “ .
Anne, you point out the problem: current methods for identifying reductions in cognition in high functioning adults is sorely lacking. The same is true for methods to help high functioning adults compensate for cognitive deficits. This impacts us MSers especially because we may experience reduced cognition (slower processing speed, need for repetition, recall difficulty) early and mid career. If for example, you were blessed with “superior” rated cognition and you pursued a certain education and career path, a reduction in your cognition below “superior”, may mean you can not keep your career. Nevertheless, Assistive tools and Cognitive rehabilitation are not offered for previously “superior” cognition group of MSers. If Tom Brady (arguably the GOAT American Football Quarterback) complained that he could no longer run fast, would he be told no worries, your physical fitness is “superior” to all other 43 year old men in the population? No, Brady would get a specially designed fitness program to help him keep his job and GOAT title. 😉. Let’s develop methods for MSers to keep their personal GOAT records…..Well designed drug trials for stimulants in working adults with MS to test improvements in job performance is a good start. Second, sleep studies in working adults with MS could be done to pinpoint how sleep impacts cognition. Third, brainstorm, crowd source, create a patient commission, anything to compile ways to help MSers compensate to keep their jobs. Anne, in sum, you are not alone. Many of us previously superiors are out there. Find some to conspire with….
My wife who got diagnosed in the summer has had 2 visits with her doctor (university hospital in the US). In terms of testing for cognitive decline, they asked her a few questions about her ability to carry out her daily work (she is a researcher). They also mentioned 3 random words and checked her ability to recall them 20 minutes later. Not sure if these are in any manner enough to measure decline.
ABLZZZ – Ask for a Neuropsychological Evaluation. It involves three appointments, one of which is 4 hours long and includes a battery of tests. I have these tests performed every other year so I have a documented history for disability purposes (work and SSI). This was one of the first tests I had performed after being diagnosed, as to gain a baseline assessment. Best of luck.
P.S. Prof. G – ignore the trolls and haters. Any post from you puts a smile on my face, regardless of the topic or rose-tinted score. I am always so surprised when individuals take out their frustrations on you and your amazing team. It’s like they think one person can solve the systemic failures of the entire MS healthcare infrastructure. Money rules everything (unfortunately), that should not be news to anyone living in the 21st century!
Thanks Tom. This is very helpful. We will check with the MS specialist during her next appointment (if my wife is willing to take the test).
Ablzz and others, i urge having a clear objective about ones reason for undertaking cognitive testing. Anne’s comment about the emotional toll cognitive testing can cause rang true with me, even though I knew I had some deficits. I did testing in hopes of getting compensatory tips. Also some understanding by family of things that are difficult for me. if one holds a professional license or certification, i also think it wise to consult with an experienced disability attorney about the impact of the test results on such licenses beforehand. And If employed in a “high profile” career position, One might consider private pay, rather than employer based insurer in the States, although its expensive. Finally, as this group may know, there is a high bar to to being deemed cognitively and or physically disabled from MS, especially if relatively young and holding advanced degrees. I will bite my tongue on my feelings about the utility of US ERISA employer based long term disability plans. ( You can google it if of the mind.). One would think that the government would be interested in funding a grant to study the percentage of MSers denied or terminated LTD benefits but still unable to work and dependent on public services. The MS Society knows that lawsuits by MSers against LTD insurers in The US federal courts are a poor reflection of the actual number of MSers denied LTD because court cases are too expensive. Neurologists are actually well placed to survey patients about their LTD and disability status, which would in turn guide policy makers about ways to reform the evaluation of MSers for disability for employment purposes.
I agree Suebee. My wife actually does not like the cognition questions and it takes a toll on her. She is an epidemiologist and fears losing her quantitative and writing abilities. Your point about a clear objective is noted. Thanks.
Please explain what we are looking at in terms of BVL in the 4 image series that you posted in this article. What indicates the loss?
How manny pwms you have 84 years old and up
And how manny with this condition
‘
I Knew it.
I Knew it and didn’t Want to know it.
You just opened a floodgate of emotions,
A Helen Keller moment.
Did it take an accident for you to revisit your unpopular observations?
I worked many years doing cognitive assessments.
The bad case scenarios are easy.
The Subtle changes are So hard to see sometimes.
Loved ones afraid, unaware or frustrated.
Insurance companies and government programs rely on checking the right boxes.
With Cognitive impairment sometimes there are no easy boxes.
Our neural messages Slow and sometimes never arrive.
The Original pathway is Damaged so your smart brain routes signals around it.
Usually unbeknownst to you.
I wrote an story called Wheelchair Repellent. Early on in my diagnosis I had to justify to Myself, old Neuro nurse, that I Needed DMT’s. I had Seen untreated Multiple Sclerosis when I worked Before DMT’s.
It was mostly about Cognitive changes I Feared the most.
I take my treatment, without fail.
Now about brain damage and evaluation, of course I worry about your accident and whether you had a little bump or sloshing of your 🧠. Focal changes can really hide when doing any Neuro cognitive assessment.
It’s hard to ask significant others of patients if they notice any changes. I do think it’s worth it to be open with the patient about your concerns, your need to evaluate and monitor, including significant other, caregiver in being honest. Also look at DMT regimen and teach patients how it helps. Great thoughts .
All correct but in my view simply yet another reason to deal with the real MS.
I had to take a raven matrix-like test (not an IQ test according to HR, yeah right) at work a few months before diagnosis and utterly failed (historically I tested in the upper 90s percentile wise). Interestingly, I aced the accompanying logical test so all may not be lost yet.