November/December 2024

November/December 2024 Issue

Immunology: Multiple Sclerosis in Older Adults
By J.E. Whilldin
Today’s Geriatric Medicine
Vol. 17 No. 6 P. 26

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Traditionally, it’s been considered a disease of younger adults because 80% of cases are diagnosed in individuals between the ages of 20 and 40 years. However, the aging of the general population combined with advances in MS treatment have resulted in an increasing number of MS patients who are older adults. In addition, MS may also be newly diagnosed in adults aged 50 years and older (late-onset MS). Clinicians and researchers have highlighted that managing MS and aging is challenging and a current unmet need in MS care.1,2

More than 50% of patients are now aged 55 years and older. However, there are no established, evidence-based guidelines for treating older MS patients.3 Recognizing the diagnostic challenges for those with late-onset MS and understanding the clinical manifestations of MS and treatment options are essential for providers who want to improve outcomes for older MS patients.

Diagnosing Late-Onset MS
Approximately 5% to 10% of patients with MS are newly diagnosed after age 50 years.4 Due to symptoms that overlap with other age-related conditions, diagnosing late-onset MS is challenging and the disease may be underrecognized or misdiagnosed. Also, compared with younger patients, older adults may present with different MS symptoms compared with younger patients. While classic MS symptoms such as motor impairment, visual disturbances, and sensory changes are still prevalent in late-onset MS, these symptoms may be attributed to aging or another more common age-related condition such as stroke, Parkinson’s disease, or Alzheimer’s disease. Cognitive impairment, gait disturbances, and fatigue can be more pronounced in older adults with MS, and distinguishing whether the cause is late-onset MS or another age-related disorder can be challenging.1,2,4

MRI of the brain and spine is the most commonly used imaging modality to diagnose MS. MRI findings in older adults with late-onset MS may be difficult to interpret due to age-related brain changes (eg, cerebrovascular disease, dementia), which can mimic or obscure MS lesions. In MRI of the spine, spinal stenosis and spondylotic myelopathy may complicate identification of MS spinal cord lesions.2

Comorbidities and MS in Older Adults
Common age-related comorbidities, like spinal arthritis, not only may impede the differential diagnosis process for older adults with late-onset MS but also can increase the disability burden for older adults who have lived with MS since being diagnosed as a younger adult. Approximately 45% of older MS patients have comorbidities.2 In addition, certain comorbidities occur at a higher rate in older adults with MS. Research has shown that the following comorbidities may be more prevalent and increase the severity of disability in older patients4,5:

• hypertension;
• high cholesterol;
• cardiovascular diseases, including ischemic heart disease, heart failure, and peripheral vascular disease;
• type 2 diabetes; and
• cerebrovascular disease.

Because older MS patients already have a below-average health status, the impact of comorbidities on their overall health and functionality is greater than for older adults without MS. Some studies have shown that cardiovascular comorbidities, such as hypertension, promoted more neurodegeneration, and that older MS patients may have a 30% greater risk of having an acute coronary event or cerebrovascular disease.6

Musculoskeletal comorbidities, such as osteoarthritis and osteoporosis, can also increase risk and disability for older MS patients. Mobility impairments, such as gait and balance issues, make older MS patients more likely to fall; osteoarthritis may further affect mobility and fall risk. In MS patients with osteoporosis, the risk for fractures from a fall are then compounded.6

Treating Older Adults With MS
Treating MS is challenging due to comorbidities and the prevalence of polypharmacy in older adults. Polypharmacy—the simultaneous use of five or more medications by a patient for one or more conditions—is an important clinical issue in geriatric care in general. Medication errors, adverse drug interactions, and increased risk for falls and hospitalization have all been linked to polypharmacy in older adults. For older adults with MS, the addition of MS medications further increases the risks associated with polypharmacy.7

Disease-modifying therapy (DMT) for MS includes medications that modulate the immune system and inflammation, such as monoclonal antibodies (eg, natalizumab) and sphingosine l-phosphate receptor modulators (eg, fingolimod). DMTs are prescribed to prevent MS-associated disability progression. The majority of clinical trial research on DMTs has been performed on patients younger than 50 years. Subsequent studies suggest that DMTs may not be as effective in older adults. DMTs may also increase the risk of severe drug-related adverse events in older adults with common comorbidities such as hypertension as well as the risk of infection. The DMTs selected for treatment of older adults should consider the patient’s overall health, comorbid conditions, and potential for adverse effects.4-6

There’s an ongoing debate regarding the long-term use of DMTs in older adults, given the lack of research on safety and efficacy in older MS patients. Researchers recommend a case-by-case approach in determining DMT use for older adults, based on their disability progression, comorbidities, radiological disease signs, disease duration, and age. Discontinuation or de-escalation of DMTs may be considered in older patients with stable disease.3,5,6

In addition to DMTs, older adults with MS may require medications for MS spasticity, pain, bladder dysfunction, and mood disorders. If they also have comorbidities, the number of medications can quickly meet the criteria for polypharmacy. The effects of polypharmacy are often not recognized by MS care providers. Periodic reviews of medications and their benefits/risks should be performed for older adults with MS to reduce the risks associated with polypharmacy and long-term DMT use. Nonpharmacological options, such as physical therapy, occupational therapy, and cognitive rehabilitation, as well as mobility aids, can help manage some MS symptoms, reduce the need for medications, and improve quality of life.5-7

Cognitive Impairment
Cognitive impairment is more common in older adults with MS than in adults of the same age without MS. It is estimated that 40% to 65% of older adults with MS may have cognitive impairment.1 Other studies have suggested that approximately 77% of older adults with MS have impairment in two or more cognitive domains, such as recent memory, attention, and visuospatial learning.2

Older adults with MS are also at higher risk for comorbidities associated with lower cognitive function. For example, research has shown a greater risk of vascular dementia and Alzheimer’s disease in older adults with MS, though the exact cause is unclear.2,6 A recent claims database analysis found that the occurrence of early-onset Alzheimer’s disease and related dementia was significantly greater in adults with MS aged 45 to 64 years and those older than 65 years compared with adults of the same age without MS.8 However, the contribution of misdiagnosis related to MS-associated cognitive impairment was not clear.6,8

In older adults with MS, distinguishing the development of Alzheimer’s disease or dementia is challenging. Research studies suggest that MS-associated cognitive
impairment may affect information processing speed, memory, and executive function; aphasia, anomia, and apraxia (speech/communication problems) are more characteristic of Alzheimer’s disease and other dementia. Routine screening for cognitive impairment and neuropsychologic testing to distinguish MS-associated cognitive impairment from dementias is recommended as part of the management strategy for older adults with MS.1,3

MS in older adults presents distinct challenges and clinical considerations. The optimal care of the older adult with MS therefore requires a multidisciplinary team, which may include neurologists, geriatricians, physical therapists, occupational therapists, social workers, urologists, psychologists/psychiatrists, and speech therapists, depending on the individual patient’s symptoms and needs.6

With the growing population of older adults with MS, further research is needed to gain a better understanding of the pathophysiological differences in MS presentation and disability progression, as well as the long-term safety and efficacy of DMTs. This research is needed to inform evidence-based guidelines geared toward optimizing treatment strategies and improving patient outcomes for older adults with MS.3

— J.E. Whilldin is a medical research analyst and writer from the Reading, Pennsylvania area.

References
1. Balusha AKA, Morrow SA. Multiple sclerosis in people over age 55. Practical Neurology. https://practicalneurology.com/articles/2021-feb/multiple-sclerosis-in-people-over-age-55. Published February 2021.

2. DiMauro KA, Swetlik C, Cohen JA. Management of multiple sclerosis in older adults: review of current evidence and future perspectives. J Neurol. 2024;271(7):3794-3805.

3. Tumani H, Coyle PK, Cárcamo C, et al. Treatment of older patients with multiple sclerosis: results of an international Delphi survey. Mult Scler J Exp Transl Clin. 2023;9(3):20552173231198588.

4. Nociti V, Romozzi M, Mirabella M. Challenges in diagnosis and therapeutic strategies in late-onset multiple sclerosis. J Pers Med. 2024;14(4):400.

5. Graves JS, Krysko KM, Hua LH, Absinta M, Franklin RJM, Segal BM. Ageing and multiple sclerosis. Lancet Neurol. 2023;22(1):66-77.

6. Macaron G, Larochelle C, Arbour N, et al. Impact of aging on treatment considerations for multiple sclerosis patients. Front Neurol. 2023;14:1197212.

7. Thelen J, Zvonarev V, Lam S, Burkhardt C, Lynch S, Bruce J. Polypharmacy in multiple sclerosis: current knowledge and future directions. Mo Med. 2021;118(3):239-245.

8. Mahmoudi E, Sadaghiyani S, Lin P, et al. Diagnosis of Alzheimer's disease and related dementia among people with multiple sclerosis: large cohort study, USA. Mult Scler Relat Disord. 2022;57:103351.