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The Impact of Ageing on Multiple Sclerosis

min read

Life expectancy is increasing worldwide. Nowadays, people live at least 6 years longer compared to 20 years ago. Improved overall lifespan and advances in pharmacological treatments have also extended the longevity of individuals with multiple sclerosis. After diagnosis, people live with MS for a longer duration. An increasing number of persons with MS are maintaining employment and enjoying a good quality of life until their retirement years [1]. However, ageing poses unique challenges to older people with MS, which demand more recognition when starting, switching, or discontinuing a treatment [1].

When people with MS get older

The brain of young people has a remarkable capacity to compensate for demyelinating events. Despite experiencing two to three times more relapses, the paediatric population recovers better compared to adults. Professor Chitnis and her colleagues explored the impact of age on recovery after relapse on two large prospective cohorts of adult and paediatric patients. They observed that children experienced a better recovery from relapses compared to adults. For every decade that elapsed, the recovery on the Expanded Disability Status Scale (EDSS) was reduced by 0.15 points [2].

As people with MS get older, the brain’s natural reserves may exhaust their capacity to compensate for further axonal degeneration [1]. Moreover, the normal process of ageing is accompanied by a weakening of the immune system, which is highlighted by the concept of “immunosenescence” [3]. Although the immune system of elderly people still works, the quality of its response is markedly different compared to young people. These elements, combined with others, contribute to the shift in MS phenotype from predominantly inflammatory to neurodegenerative [1].

Chronological age – defined by the date of birth – is, in fact, strongly associated with the clinical course of multiple sclerosis and with the rate of disability accrual [4]. In most cases, MS is diagnosed between 20 and 40 years. More than 60% of people with MS develop progression prior to reaching 75 years old [5]. With ageing the disease course can change. Inflammatory disease activity wanes. Elderly populations with MS exhibit fewer relapses and less focal activity captured by magnetic resonance imaging (MRI). On the contrary, chances of detecting smouldering lesions – associated with slow but continuous demyelination and neurodegeneration – increase with age and disease duration [6, 7]. We also know today that a few persons – less than 5% – are diagnosed with MS beyond the age of 50 years old (late-onset; LOMS) and even past the age of 60 – around 0,5% (very-late-onset; VLOMS) [8]. Typically, when MS is diagnosed late in life, disability progresses faster, and the disease outcomes become more challenging [8].

BICAMS can help detect cognitive impairment in MS

Ageing may be normally accompanied by changes of some cognitive abilities. This represents a particular concern when treating older people with MS [9]. Ralph Benedict, professor of neurology at the University at Buffalo, told us, “The Brief International Cognitive Assessment for MS (BICAMS) battery includes very sensitive measures to early detect cognitive impairment in MS, such as tasks that assess processing speed and new learning”. Researchers and clinicians are also addressing important clinical concerns regarding comorbid neurological diseases. Interestingly, the degree of cognitive decline in persons with MS does not seem to be amplified by ageing. Therefore, an acceleration of cognitive impairment in older people with MS should solicit an evaluation for concomitant cognitive diseases [10]. “Distinguishing between cognitive impairment in elderly population with MS and early symptoms of Alzheimer’s disease (AD) or amnestic mild cognitive impairment (aMCI) is an important concern that we are trying to address. At a clinical level, language disorders, such as difficulties in semantic fluency (e.g. name as many animals as you can in 60 seconds) or naming drawings, can signal a comorbidity with AD. Likewise, rapid forgetting, and significant deficits not only in recalling, but also in recognising an information that was presented earlier are akin to AD”, Benedict adds.

Switching or stopping MS therapies in later life

Despite the increasing number of older people living with MS, benefits and risks of therapeutic regimens are still poorly understood in this population. Indeed, clinical trials have rarely included individuals with MS over 55 years old. This has determined an important age difference between the people of advanced age with MS who receive the therapies in the real-world and people who participated to the clinical trials [11]. “Existing medications enable to control active inflammation. They are very potent, and effective in preventing acute attacks (i.e. relapses) and new lesions. However, as time goes on, mostly with ageing, but also with disease duration, the benefits of these medications decrease. Currently, disease-modifying therapies cannot prevent the risk for progression. Progression can be related to acute relapses but can also occur independently from acute events. The so-called PIRA (progression independent of relapse activity) or smouldering MS can also start early in patients classified as relapsing-remitting”, Bianca Weinstock-Guttman, professor of neurology at the University at Buffalo told us in a recent interview, “In addition to anti-inflammatory therapies, we need treatments that enable to control progression, while minimising the adverse effects for older people. In fact, ageing and accrual of disability are associated with more vulnerability to some of the side effects related to anti-inflammatory therapies – especially risks of infections”.

With advancing age, inflammatory activity diminishes, whereas the risk of infections associated with several MS therapies may increase [11]. Changes of the immune system related to age (i.e. immunosenescence) and the consequent state of low-grade, chronic inflammation, termed “inflamm-aging” [12] may be strongly associated with the loss of efficacy of disease-modifying therapies (DMTs) as well as with the higher risk of adverse events observed in older patients with MS [11]. Therefore, patients of advanced age should discuss with their neurologist the treatment-associated risks, knowing that the data on the efficacy of DMTs in their population is insufficient. Older people with MS who have shown no evidence of disease activity for several years under DMTs may contemplate, in consultation with their neurologist, stopping the treatment [11].

Professor John Corboy and his colleagues ran a controlled trial of therapy discontinuation – DISCOMS – on 259 people of 55 years old or older with MS, to evaluate the risk of new disease activity in patients who continued or discontinued the treatments. Individuals with MS with no recent inflammatory activity were randomly assigned to two groups. 50% of participants continued the treatments and 50% discontinued. Clinically, there was modest disease activity overall and no difference was observed in relapses or disability progression between the two groups. However, a small increased risk of new MRI activity – one or two new brain MRI lesions – was observed among the patients who discontinued [13].

“We still need something else, as add-on to ongoing therapies or something else on its own”, Professor Weinstock-Guttman continues, “At the moment, we talk with our older patients. We share the latest available information and try to align with each patient’s needs. Some older people with MS are willing to transition from immunosuppressive treatments to immunomodulatory, oral therapies. However, most of our patients tend to consider discontinuing treatment in their 70s. If they have remained stable for many years with no prior relapses and no detected changes on MRI, we might discontinue the treatment and perform an annual MRI to ensure there are no new lesions”. Further clinical trials are underway. In the meantime, healthcare professionals and patients work together to evaluate existing options and take shared decisions.

Promoting continued advances in research

The MS scientific community continually carries out a wealth of research, with the overall aim of improving patient outcomes and quality of life. Such research deepens our understanding of the disease, which will ultimately enable us to take a step closer to the provision of personalised care, with the potential to halt disease progression without jeopardising patient health. The exchanges of skills and information that occur between healthcare professionals at events such as the 9th Joint ECTRIMS/ACTRIMS Congress in Milan, Italy are invaluable, and can only serve to further improve our knowledge of MS and how best to manage patients.


ECTRIMS Insights articles are produced with the intent of being a neutral source of information sharing and objective analysis for the MS and neuroscience community. Unless otherwise stated, cited information in our articles does equivocate official endorsement from ECTRIMS.


Written by Stefania de Vito

Special thanks to Bianca Weinstock-Guttman and Ralph Benedict (University at Buffalo) for their insights.


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