This study indicates that rates of brain atrophy are affected by age and that they should be considered. One thinks that would be wise, but one wonders what this would do to the powering of studies (i.e. how big they have to be to find a difference). Trials are difficult to recruit and take years to achieve and therefore layering additional elements could have implications for size. I think another pressing issue is to really determine what measures should be monitored…as I have suggested previously a key element is to determine what measures should be collected e.g. I think brain atrophy is tainted as it can get bigger before shrinking. Bad outcome measures mean failed studies and this delayed treatments from arriving.
Kaçar S, van Nederpelt DR, Jelgerhuis JR, Coerver EME, Killestein J, Sormani MP, Ciccarelli O, Arnold DL, van Kempen ZLE, Uitdehaag BMJ, Barkhof F, Koch MW, Schoonheim MM, Eshaghi A, Strijbis EMM. Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2026 Feb 4:jnnp-2025-337779. doi: 10.1136/jnnp-2025-337779.
Background: Brain atrophy is increasingly used as an outcome measure in clinical trials in relapsing-remitting multiple sclerosis (RRMS), but little is known about how chronological age interacts with MS-specific effects. For instance, while annual brain atrophy rates typically increase with age in healthy individuals, MS patients tend to exhibit decreasing atrophy rates over time.
Methods: We investigated the relationship between age and brain volume in a large dataset of 4241 trial participants with RRMS. We used pooled individual-participant data from phase 3 clinical trials with 96 weeks follow-up, which included both active treatment and placebo/comparator arms. Participants were categorised into seven groups based on chronological age (18-24 years, 25-30 years, 31-35 years, 36-40 years, 41-45 years, 46-50 years, 51-56 years). We performed multilevel linear mixed-effects regression analyses to examine differences between age groups in normalised whole brain volume (NWBV), thalamus grey matter volume (NThGMV), grey matter volume (NGMV) and white matter volume at baseline and their changes over follow-up. We also studied how disease duration influenced these relationships using similar models.
Results: Older participants showed significantly lower NWBV, NGMV and NThGMV at baseline than younger participants. Most importantly, older participants exhibited lower rates of atrophy during follow-up, particularly in the thalamus. This association was consistent across all disease duration subgroups.
Conclusions: Older participants had more severe atrophy when enrolled into trials, but slower (thalamic) atrophy rates, independent of disease duration over time. Together, these findings emphasise that age should be taken into account when designing clinical trials that use brain atrophy as an outcome measure.
Source: multiple-sclerosis-research.org