Sunday, 10 May 2015

ClinicSpeak: cognitive reserve and education

Do you know how much cognitive reserve you have? #ClinicSpeak #MSBlog #MSResearch

"The big R in MS is for RESERVE as in reserve capacity. It seems as if the same factors that protect the general population from developing Alzheimer's disease also protect MSers getting MS-related dementia; one is cognitive reserve. It is known in the dementia field that higher education protects you from developing age-related dementia. In the study below reports a similar observation in MS; MSers with higher education have less cognitive deficits than MSers without higher education."

"Importantly cognitive impairment in this study correlated with physical disability (EDSS) and hence is another argument to try and prevent MSers becoming disabled. I suspect that cognitive impairment actually is at the vanguard of progressive MS and if looked for occurs long before physical disability emerges. MSers don't complain of cognitive problems early on because they adapt to the impairments. One of the consequence of this adaption is cognitive fatigue, which almost certainly explains the high unemployment rates in early MS, when MSers have relatively low EDSS scores. It is clear that cognitive impairment and its pathological correlate, gray matter atrophy, are present in a large number of MSers at presentation or even in the asymptomatic phase of MS (radiologically-isolated syndrome or RIS phase). All the emerging data on early cognitive impairment MS is driving a change in treatment strategy towards NEDA-4 (no evident disease activity) with a focus on trying to normalise the brain volume loss in MS; i.e. limiting or preventing end-organ damage. It is quite clear from several extension studies that brain lost due to a failure to initiate DMTs early is brain lost forever. This is why I support early effective treatment; either an induction or maintenance-escalation strategy. If you go the latter route it is essential that your subclinical MS activity is monitored so that your therapy can be changed if you are not responding to a particular class of drug. We are now firmly in the era of treat-2-target."

"MSers reading this post who have progressive MS will say what about me? If you have been following this blog for sometime you will have heard me talk about combination therapies, therapeutic lag, asynchronous progressive MS and the length-dependent axonopathy hypothesis. I truly believe that if I am correct regarding these observations it will lead to effective treatments for progressive MS. We haven't given up on you; we have to step back, pause, learn from our mistakes and try new strategies."

"Please don't forget there is a lot you can do to improve your brain health. I have posted on this before. The following is my list of things to do:
  1. Exercise regularly if you can; aerobic exercise 3-4x per week.
  2. Improve your diet; I recommend the British Heart Foundation Diet or a Mediterranean diet
  3. Keep yourself mentally active; I am not sure that the evidence of brain training is robust enough to be prescribed to MSers, but it makes sense. 
  4. Stop smoking.
  5. Improve your sleep hygiene.
  6. Review what drugs your are on; many of the drugs we prescribe to treat the symptoms of MS make cognitive impairment worse.
  7. Actively manage any co-morbidities you may have, in particular high blood pressure, diabetes, obesity and high cholesterol.
  8. Depression, low mood, anxiety and stress; if you are depressed or anxious please seek advice and treatment. Depression and anxiety affects cognitive function. Try and manage levels of stress.
  9. Invest in social capital; keep working on your relationships with your family and friends. Social isolation is not good for cognitive functioning and the factors that impact on cognition.
The above list is easier to say than do. Any ideas on how to nudge the greater MSer population into adopting a healthy lifestyle are welcome."

Epub: Martins Da Silva et al. Cognitive reserve in multiple sclerosis: Protective effects of education. Mult Scler. 2015. pii: 1352458515581874.

BACKGROUND: Recent data suggest that cognitive reserve modulates the adverse effects of MS pathology on cognitive functioning; however, the protective effects of education in MS are still unclear.

OBJECTIVE: To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features.

METHODS: A total of 419 MSers and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MSers' NP scores were adjusted for sex, age and education; and the estimated 5th percentile (or 95th percentile, when appropriate) was used to identify any deficits. MSers also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated.

RESULTS: MSers with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles.

CONCLUSIONS: These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.


  1. Does Lemtrada stabilise cognitive decline as well?

  2. Dr Dr, stating the obvious, MS drains the reserve capacity pretty damn quickly. From a starting point of top of the tree A* academically and physically to EDSS 5.5 at diagnosis. Suggestions 1,2,5,6,8 and 9 are really quite farcical. Those goals are an everyday challenge that no one with MS needs to be given a heads up on. Seriously this is a beast of a disease, no one has a choice where their EDSS starts.You are implying control over progression where none exists. Each to their own. You can't educate yourself out of the crap unfortunately and who knew it was going to be you in it !

  3. CBT cognitive behavioural therapy is good for depression, stress and anxiety. Through CBT it teaches about awareness and assertiveness. Mindfulness meditation is an element of CBT.

  4. When this vile disease starts working itself up the EDSS scale there is nothing we can do. Eating our greens and doing the crossword won't make a jot of difference. EBV needs to be addressed but the focus on EAE means that the cause of this disease won't be addressed for years. Do they use a mouse disease model for cancer?

  5. Well...I am a very introverted person. If I would increase my "social connections" I would be stressed out quite fast.
    The first thing to do: knowing who you are or ask a professional to do some tests to tell. Then you could come up with a "personalized" program for this person. These tests already exist and could be implemented into a regular consultation.

  6. I think these are good suggestions for anyone; you've said that before. But I always question the mental activity advice. I get that extended education, puzzles, playing music, etc are challenging, but does the brain really know the difference between working out a tough equation and trying to make out that odd shape down the road? That is, when are we not cognitively active, really?

    1. There are plenty of studies around with Alzheimer patients that show that the more "engaged" forms of mental activity have positive impacts on cognition. While MS is a different disease there is no problem relating such mental activities to maintaining or improving function. I think you would also find that trying to work out what that "odd shape down the road" is would be using different brain pathways to those involved in mental exercises such as puzzles etc. It's really very simple - use it or lose it!!! (I just wish I was more capable of the physical exercise aspects - I'm struggling to use it, and I know I'm gradually losing it in that department...bloody MS!)

  7. I've returned to university to retrain in Psychology which has been great for being mentally engaged. One of the most interesting things that has come up is the role of enrichment vs exercise in neurogenesis and neuroplasticity (Voss et al. 2013). Exercise and the hormones released afterwards seem to be the key, generating just as much improvement as enriched environments, and indeed benefits seen for enriched environments for rats seem to based on their physical interaction with that environment ie. exercise! There's a reason Prof G and co. keep urging us to explore exercise options.

    What is the downside to making an effort on these fronts? Yes, these things are challenges and it can be quite difficult, but that's life. On the other side of the coin some of them can be quite fun! We may not be as good as we once were, but that shouldn't really stop us from doing what we can to maximise what we have.

  8. You may not believe me, but I did all nine of the suggestions on your list and yes it does work. I was educated to GCE O' level standard, Left school at a time when you could learn on the job rather than go to university. In my job there were loads of things that were constantly changing and new things to learn and courses to go on. Having said this, I think I probably had a good memory to start with.

  9. Speaking two languages is very beneficial. But I generally prefer the company of plants to people. As Freud said: "Flowers are restful to look at. They have neither emotions nor conflicts." I personally recommend growing cacti and talking to them in German.

    Yes, exercise, sleeping, not smoking, good diet and actually using your brain are beneficial factors. But this ought to be obvious to everyone.

  10. It's not clear to me whether this paper talks about causality or just correlation.
    I want to emphasize this point for two reasons:
    - Correlation is not enough!
    - If correlation is enough I should believe, just as an example, that the Swank diet works. Am I right? Any Doc on that?

  11. I find MOOC's (massive open online courses) are helping me with my MS, learning and memory.
    Through having MS I find many course subjects interesting in subjects related in some way to MS or changes in lifestyle that can help MS.
    Courses such as fundmentals of neuroscience, the immune system, human physiology, nutrition, stress management and resilience, introductory psychology, happiness inc covering mindfulness and how MRI scanners work.
    These short courses can be audited for free, from home and are delivered by global universities. They also have discussion forums.

    1. What about Barts delivering a MOOC on MS? This could raise awareness of MS and as the online courses are free could help MSers in countries with less rescources regarding MS. Treating MS requires a holistic approach and not only DMT's.
      Johns Hopkins University have delivered an online MOOC called Living with Dementia: Impact on Individuals, Caregivers, Communities and Societies. I've no idea how much it would cost to deliver a course.


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