Atrophy prevention correlates with cognition

[NHE]

Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Cognition in Multiple Sclerosis
Ann Neurol. 2023 Nov;94(5):925-932.

Objective: The purpose of this study was to evaluate the extent to which treatment effect on magnetic resonance imaging (MRI)-derived measures of brain atrophy and focal lesions can mediate, at the trial level, the treatment effect on cognitive outcomes in multiple sclerosis (MS).

Methods: We collected all published randomized clinical trials in MS lasting at least 2 years and including as end points: active MRI lesions (defined as new/enlarging T2 lesions), brain atrophy (defined as a change in brain volume between month 12 and month 24), and change in cognitive performance (assessed by the Paced Auditory Serial Addition Test [PASAT]). Relative reductions were used to quantify the treatment effect on MRI markers (lesions and atrophy), whereas the standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used to quantify the treatment effects on cognition. A linear regression, weighted for trial size, was used to assess the relationship between the treatment effects on MRI markers and cognition.

Results: Fourteen trials including more than 8,813 patients with MS were included in the meta-regression. Treatment effect on cognition was strongly associated with the treatment effect on brain atrophy (R2 = 0.79, p < 0.001), but was not correlated with the treatment effect on active MRI lesions (R2 = 0.16, p = 0.14).

Interpretation: Results reported here suggest that brain atrophy, a well-established MRI marker in MS clinical trials, can be used as a main outcome for clinical trials with drugs targeting cognitive impairment and neurodegeneration.