Odour discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis

Abstract

Background: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS). Objective: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course. Methods: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck. Clinical, bi-annual visits assessed patients’ history and Expanded Disability Status Scale (EDSS) score. DI and cognitive function were assessed at baseline (BL), Year 1 (Y1), Year 2 (Y2) and Year 6 (Y6) by the ‘Sniffin’ Sticks’/Symbol Digit Modalities Test. Results: Around 92 of 139 patients were available for Y6 follow-up. Mean DI scores significantly decreased over time (BL = 27.8, Y1 = 27.5, Y2 = 26.3 and Y6 = 26.3; p < 0.001) and negatively correlated with patients’ age ( rs = −0.120, p = 0.032) and disease duration ( rs = −0.103, p = 0.041). Multivariable regression analyses revealed that lower absolute DI scores and larger DI score loss over time were associated with higher probability of EDSS worsening (per −1 point: hazard ratio (HR) = 1.40 (1.16–1.68) and 2.34 (1.27–4.21)), progression independent of relapse activity (PIRA) (HR = 1.49 (1.20–1.85) and 2.22 (1.33–3.31)) and cognitive deterioration (HR = 1.75 (1.35–2.27) and 4.29 (1.26–2.84)) at Y6, but not with time to first relapse. Conclusion: Odour DI is an irreversible marker of neuroaxonal damage, associated with PIRA, cognitive deterioration and EDSS worsening.