Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis

Area of Science:

• Neurology
• Clinical Trials
• Neuroimaging

Background:

• Brain atrophy is a key outcome in relapsing-remitting multiple sclerosis (RRMS) trials.
• The interaction between chronological age and MS-specific effects on brain atrophy is not well understood.
• While healthy aging typically shows increased atrophy, MS patients may exhibit decreasing rates.

Purpose of the Study:

• To investigate the relationship between chronological age and brain volume changes in RRMS.
• To determine how age influences brain atrophy rates in clinical trial participants.
• To assess the impact of disease duration on age-related atrophy patterns.

Main Methods:

• Analysis of pooled data from 4241 RRMS trial participants (96-week follow-up).
• Categorization into seven age groups (18-56 years).
• Multilevel linear mixed-effects regression models examining normalized whole brain volume (NWBV), thalamus grey matter volume (NThGMV), grey matter volume (NGMV), and white matter volume at baseline and over time.

Main Results:

• Older participants had lower baseline NWBV, NGMV, and NThGMV compared to younger participants.
• Older participants demonstrated significantly lower rates of brain atrophy during follow-up, especially in the thalamus.
• These age-related differences in atrophy rates were consistent across all disease duration subgroups.

Conclusions:

• Older RRMS patients present with greater baseline atrophy but experience slower rates of thalamic atrophy over time.
• Age is an independent factor influencing brain atrophy progression in RRMS.
• Chronological age must be considered when designing RRMS clinical trials using brain atrophy as an outcome measure.