Age plays role in how RRMS affects brain volume over time
Atrophy progresses more slowly with age, study finds
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The two halves of a brain are shown.
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Brain atrophy in RRMS varies significantly with age.
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Older patients start with smaller brain volumes but see slower atrophy rates over time.
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Age must be considered in clinical trial design and interpretation for DMTs.
Brain atrophy, or the loss of brain volume, in people with relapsing-remitting multiple sclerosis (RRMS) appears to slow with age, according to data from more than 4,000 patients who took part in Phase 3 clinical trials.
Researchers found that older adults with RRMS had significantly smaller brain volumes than younger participants at the start of the trials. However, over nearly two years of follow-up, older adults showed lower rates of brain atrophy than younger patients, regardless of disease duration.
The findings could have important implications for clinical trials that use changes in brain volume as the main outcome to assess the efficacy of new disease-modifying therapies (DMTs). For example, because older patients have lower rates of brain atrophy, trials may need to include larger patient groups to detect meaningful treatment effects in some regions. The results also suggest that benefits seen in younger patients may not always translate to older adults with MS.
“Age is a key modifier of … atrophy measures in RRMS. It should be explicitly considered in trial design, sample size calculations and in the interpretation of treatment effects across different age groups,” the researchers wrote.
The study, “Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.
Brain shrinkage, normal with aging, is faster for MS patients
Multiple sclerosis (MS) occurs when the immune system mistakenly healthy attacks myelin, a protective coating around nerve cells that helps them communicate efficiently. As myelin is lost and nerve cells become damaged and die, the brain gradually shrinks.
Progressive loss of brain volume is a normal part of aging, but people with MS experience substantially faster brain shrinkage.
Many MS trials have used brain atrophy as a primary measure evaluating the efficacy of new DMTs. But it may be difficult to distinguish age-related brain changes from MS-specific damage, especially as patients age, which may complicate study interpretation.
To explore how age may affect brain volume measures in people with MS, a team led by researchers in the Netherlands examined data from 4,241 people with RRMS who had been followed for nearly two years in a previous Phase 3 clinical trial.
Because the study’s goal was to examine overall patterns of brain atrophy across different ages rather than to compare treatments, the team pooled data from all studies.
Most participants were women (66.4%), and the mean age at study start was 37.3. For the analysis, participants were divided into seven age groups — each covering about five years — starting with young adults, ages 18-24, and continuing to the oldest group, ages 51-56. As expected, older participants had a longer disease duration than younger participants.
At the start of the trials, brain volume varied by age. Compared with participants ages 25-30 — the study’s reference group — all older groups had significantly smaller brain volumes across several major brain regions, “a pattern that reflects a linear decline with increasing age,” the researchers wrote.
These differences were seen regardless of how long someone had been living with MS.
Over nearly two years of follow-up, brain atrophy progressed in all age groups. However, older participants showed the lowest rates of brain shrinkage over time, especially in the thalamus, a deep brain region often affected early in MS.
This age-related pattern remained consistent, even after researchers accounted for other factors that might influence brain volume loss, including disease duration. The findings align with previous studies showing “that age significantly influences brain volume trajectories in MS,” the researchers wrote.
The researchers noted that this pattern may partly reflect how aging alters the biological course of MS. In younger adults, MS is usually driven by more active inflammation, which may contribute to faster rates of brain atrophy. With age, the disease is thought to shift toward more gradual, long-term nerve damage — a change that may help explain why brain atrophy appeared to progress more slowly in older participants over the study period.
“These findings underscore the importance of accounting for age when analysing brain volume and designing clinical trials,” the researchers concluded.
