Ageing and MS

Topics for discussion

Age is highly a relevant factor in the clinical course of multiple sclerosis. This webinar will discuss the role of ageing in MS, how greater knowledge of this might halt non-relapse related progression and how the somatic and reproductive ageing processes are linked with the development of progressive MS. It will cover how comorbidities affect outcomes and where we as clinicians can improve outcomes through prevention and education for people with MS. The webinar will present an overview of the risks and benefits of disease modifying therapies in older adults and the comprehensive assessment priorities for the older person with MS.

Objectives

• Understand the role of ageing in MS and how this knowledge might halt non-relapse related progression
• How do co-morbidities impact the older person with MS
• Understanding of the comprehensive assessment in the older person with MS
• Overview of disease modifying therapies in the older patient

Summary

Aging and multiple sclerosis

The demographics of people living with MS are changing. In the United States, more than half of people with the condition are now over the age of 55, reflective of the general population.

In addition, the age at which people are being diagnosed is increasing. Dr Wallace Brownlee, consultant neurologist and clinical lead at The National Hospital for Neurology and Neurosurgery in London, explained that late-onset MS, or diagnosis over the age of 50, was becoming increasingly common, particularly among women.

“This has a profound impact on MS disease course,” he said. As people with MS get older, relapse rate fall and there are fewer active lesions on MRI, yet there is worse recovery from relapses and an increased risk of a progressive disease course.

Driving factors

There are various possible factors at play here. These include somatic aging, which is related to the changes that happen to the body as it gets older. Leukocyte telomere length is associated with biological age, and shorter lengths have been linked to higher disability, progressive disease course and lower brain volume in MS. Possible mechanisms of this include inflammaging, which is an age-related chronic, low-grade state of inflammation.

Immunosenescence, or age-related changes to immune function such as reduced lymphocyte function, could explain why older people are less likely to experience relapses, Wallace said. He also explained that estrogen has a neuroprotective effect in both men and women, yet menopause leads to a sudden drop in levels of the hormone.

MS, aging, and co-morbidities

The burden of co-morbidities in people with MS increases with age, and these can have a big impact. They can affect relapse rates, physical disability, and cognitive impairment, as well as quality of life, employment or social participation, and mortality.

“There are three common age-related co-morbidities that are important and that we could modify,” said Wallace.

These are vascular disease, infection, and osteoporosis. Healthcare professionals (HCPs), he went on, should be thinking about blood pressure and cholesterol testing, vaccination, and bone screening. “Addressing age-related co-morbidities is a key part of comprehensive MS care,” he said.

Comprehensive assessment

When approaching assessment of older people with MS, all or most areas that are covered with a younger person should be included, said Michelle Davies, Dorset MS service lead andspecialist practitioner at the University Hospitals Dorset NHS Foundation Trust.

However, there are some areas that will required a higher degree of focus in this patient group. These are related to co-morbidities and polypharmacy, frailty, mental health, and known factors for healthy aging. “Don’t wait for them to get old. Think about things you can do early,” said Michelle.

The more conditions people have, the more medication they will be taking, she went on. “Some of these can negatively impact MS impairment.” Anticholinergics, for example, can cause constipation and reduce cognitive function.

Frailty is an age-related syndrome that can affect anyone, but long-term conditions can sometimes act as a mask, meaning healthcare teams “do not always pick up on it”. Signs and symptoms, such as falls, immobility, reduced strength and walking speed, can all overlap with MS. Michelle recommended HCPs “think proactively as well as reactively” around focus areas such as diet and nutrition, weight, energy levels, muscle strength, bone health, and balance.

She went on to say that living with a long-term condition increases the incidence of, and can exacerbate, mental health conditions. MS teams, then, should look out for depression and anxiety, as well as the mental health of carers. It is also important to remember that the symptoms of dementia can be similar to those of MS.

Older people are especially vulnerable to loneliness and social isolation, which can be compounded by the barriers to social participation that can be associated with MS. “These are things we should be talking about,” said Michelle.

Advising on healthy aging is also crucial. That means talking about modifiable risk factors, such as exercise, eating a balanced diet, not smoking, and having meaningful social contact, as well as proactively managing their health and co-morbidities.

Summing up, Michelle said it was “not just about birthdays”. “There are young old people and old young people. You have to time your interventions and your assessments according to how someone is presenting.”

Disease modifying therapies in older patients

Clinical trial data suggests that DMTs do not work as effectively in older people as younger people with MS. However, it is important to remember that such studies usually exclude older people, and that there is a difference between chronological and biological age, said Rachel Dorsey-Campbell, senior lead pharmacist for neurosciences, at Imperial College Healthcare NHS Trust.

She added that data suggests that the longer someone is on a DMT, and the more disabled they are, the more likely they are to develop infection. In terms of malignancy, the data is mixed, but there are signals that older people receiving DMTs may be more at risk, she added. However, there are no guidelines on if, when, or how to discontinue treatment.

“I think we should be thinking about de-escalating the risk,” said Rachel. “That might mean giving them a lower risk therapy, by switching them from a highly effective immunosuppressive to a lower risk one, or adjusting dosing.”

Considerations when discontinuing a DMT vary by agent, she went on. With S1P modulators and integrin inhibitors, there is a potential for rebound activity, so HCPs may want to think about offering a bridging therapy. With anti-CD20s, there is no risk of rebound, though there may be an immune reconstitution effect. Options here might include extended interval dosing or reduced dosing, rather than “a hard stop”, explained Rachel.

Treating the older person with MS

Polypharmacy is common, particularly as people get older, Rachel went on, adding that MS teams should review medications and consider de-prescribing. “It is incumbent on us, as HCPs, to think about what drugs we should stop, not just what drugs should we start,” she added.

Rachel said that there was “a lot to think about” when assessing older people living with MS. “But we certainly need to be treating the individual patient, and not just their age,” she added, reiterating Michelle’s point that “there are young old people and old young people”.