“Ageing comes with many issues in multiple sclerosis (MS): progression, comorbidities, cognition problems and response to treatment”, Pierre Duquette (Department of Neuroscience, University of Montreal, Canada), the chair of the Hot Topic session on ageing in MS summarised in his introduction during this year’s “2020 joint ACTRIMS/ECTRIMS meeting”. During the session, three renowned experts shared their expertise on different aspects of ageing in MS.
Age-related MS phenotypes
In the first presentation, Burcu Zeydan (Departments of Radiology and Neurology, Mayo Clinic, United States) talked about ageing and MS phenotypes. The phases of MS, including the relapsing-remitting and progressive phases, are sequential and overlapping.1 The evolution between the two phases usually happens at a mean age of 45 years. “In addition to the primary disease process, we are also racing against ageing mechanisms in MS”, Dr Zeydan stated. Age-related oligodendroglia-, astrocyte- and plaque-senescence are all likely mechanisms that contribute to the clinical senescence phenotype of the disease. Recent study data from Dr Zeydan’s own group and others confirmed that both central nervous system (CNS) reserve, as well as recovery from relapses, decrease with age. Furthermore, it was shown that clinical and subclinical relapses peak and decrease, and that in general, the pathology of MS changes with age. At the end of her presentation, Dr Zeydan concluded that the relationship between ageing mechanisms and clinical phenotypes must be better understood, and clinical trials might need to be re-assessed to be able to provide age-specific treatment recommendations for MS patients.
MRIs and ageing in MS
In the following presentation, Olga Ciccarelli (UCL Institute of Neurology, Queen Square MS Centre London, United Kingdom) elaborated on the use of magnetic resonance imaging (MRI) when looking at ageing and MS. In MRIs, it is crucial that paraventricular lesions or lesions in deep grey matter structure are not counted as MS lesions, as they can be classified as normal age-related changes. On the contrary, brain volume loss can be observed in MRI scans of MS patients (0.5-1% per year), but also to some extent in healthy subjects (0.2–0.4% per year). “In MS patients, there is an additional 0.61 years of brain ageing per year”, Dr Ciccarelli stated during her presentation, impressively showing the effects of the disease on brain structure. To conclude, she mentioned that it would – according to the latest research – be important to adjust MRI cut-offs according to the patient’s age.
In the last presentation of the session, Catherine Larochelle (University of Montreal, Canada) gave her insights on the immunological perspective of ageing in MS patients. It is currently suggested that immunosenescence contributes to the impact of ageing on the course of MS and also to the worsened response to disease-modifying treatments (DMTs) with age. Thus, Dr Larochelle and her team designed a study to characterise age-sensitive immune markers in MS patients. Their hypothesis suggests the presence of fewer active anti‑inflammatory and repair mechanisms and more inflammatory mediators. Indeed, their preliminary results point towards such a correlation, but large discrepancies were seen between male and female patients, warranting further analysis. Additional analyses will also show whether or not MS is associated with immunosenescence and will clarify the impact of DMTs. According to Dr Larochelle, a promising option for targeting immunosenescence could be methionine restriction, which alters methylation patterns in immune cells and is effective against neurodegeneration in animal models. However, the future will determine if this will also be applicable in human MS patients.
For more coverage from “2020 joint ACTRIMS/ECTRIMS meeting” please click here.