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.
Crowdfunding: Have you contributed to Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?