NEFL and Cognitive impairment: Similarly, in the phase 2 Lamotrigine trial investigating neuroprotection in SPMS, higher CSF NfH concentrations were associated with lower PASAT scores.27 Importantly, cognitive impairment in MS is primarily driven by grey matter damage.30 In our study, higher NfL and NfH were variably correlated with lower SDMT, PASAT, and whole and grey matter volumes, suggesting that CSF neurofilaments reflect brain volume loss and reduced information processing speed, which are linked to the underlying neurodegenerative process.