Effect of Aging and MS

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People with MS have been living longer than they did 40-50 years ago, especially since the introduction of disease-modifying medications. Researchers have noted that life expectancy and average age of persons with MS have increased significantly during the past two decades, but remains on average seven years less than the general population. Studies have shown that increased mortality rates are often related to comorbidities, such as diabetes, coronary heart disease, depression, lung disease, or infectious diseases. (Marrie 2015)

As people with MS live longer, they begin to face more of the conditions traditionally associated with aging or advanced aged. Sometimes it can be difficult to distinguish between concerns that are related to MS and those that may simply be related to aging. In a recent literature review, researchers discuss several factors related to aging and MS, including common comorbidities, that can help healthcare professionals distinguish between the effects of normal aging, relentless MS disease progression, a new disease common in aging, or some combination of these (Sanai et al, 2015).

Influence of age on MS disease course

Older individuals with MS are more likely to have a progressive form of the disease (primary progressive (PPMS), 29 percent; secondary progressive (SPMS), 26 percent; or progressive relapsing (PRMS), 8 percent), compared to younger MS patients of whom 57 percent have RRMS. Older age at onset of MS—after 50 years for late-onset MS (LOMS) or after 60 years for very late-onset MS (VLOMS)—is associated with increased risk of PPMS, earlier transition to SPMS, and faster accumulation of disability. Patients diagnosed after the age of 60 are more likely to have motor and coordination symptoms at onset and less likely to have visual or sensory symptoms. Delays in diagnosis may be caused by cardiovascular comorbidities. The percentage of women diagnosed with MS declines as age increases.

Inflammation and aging

Multiple sclerosis is an inflammatory disease, particularly so in its earlier stages. But normal aging is also associated with a chronic, systemic low-grade inflammation influenced by the production of pro-inflammatory cytokines and inflammatory markers. Unbalanced immune responses contribute to the development of age-related diseases such as cardiovascular conditions, autoimmune diseases, cancers, and increased susceptibility to bacterial and viral infections (Sanai et al, 2016). Additionally, there are changes seen in CD4+ T-regulatory cells in the aging population. Research suggests that the already misfiring immune system in people with MS may cause these age-related inflammatory changes to appear at an earlier age, helping to drive the transition from RRMS to SPMS.

Effects of aging versus MS on the brain

Acute attacks of CNS inflammation in multiple sclerosis are marked by clinical relapses and new lesion activity that can be seen with an MRI. However, white matter lesions may appear in the brain due to vascular changes associated with normal aging. Even in the early stages of MS, irreversible neurodegeneration (nerve death) can lead to T1 lesions called “black holes” and brain atrophy (loss of brain volume). Normal aging can also lead to brain atrophy. However, the tissue loss due to MS results in a 0.7–1.0 percent loss of brain volume per year in the average person with MS, compared to 0.1–0.3 percent loss per year from normal aging in healthy persons.

With aging, the CNS accumulates iron deposits that causes oxidative stress and cell death, contributing toward neurodegeneration. Researchers have noted that iron accumulation is an important feature of MS lesion formation and may be due to the destruction of iron-rich oligodendrocytes. As MS progresses and patients become older, the body becomes less able to remyelinate and repair nerve damage. Studies have suggested that aging modifies the tissue response to inflammatory injury. Sanai et al report that because these age-related changes in myelination coincide with the approximate average age at which people with MS reach progression (mean age: 38-45 years), it has been proposed that the loss of remyelinating capacity with aging contributes to the transition to SPMS. Hence, MS may be “a disorder of a single stage, with an apparent shift in phenotype driven not by a fundamental change in pathology but by age-related changes.”

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Sources
Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015 Jul 21;85(3):240-7. doi: 10.1212/WNL.0000000000001718. Epub 2015 May 27.

Sanai SA, Saini V, Benedict RH, et al. Aging and multiple sclerosis. Mult Scler. 2016 Feb 19. pii: 1352458516634871. [Epub ahead of print]