Symptoms of depression and anxiety are early predictors of multi-domain disability progression in progressive MS

INTRODUCTION: In multiple sclerosis (MS), depression and anxiety are common, yet their relation to disease progression is unclear. We investigated whether Hospital Anxiety and Depression Scale (HADS) symptoms predict neurological disability progression.

METHODS: In our prospective cohort of people with primary progressive MS (PPMS), depressive and anxiety symptoms were assessed using HADS. Disability progression at 1 and 2 years was assessed using three predefined endpoints: (1) Expanded Disability Status Scale (EDSS), (2) a three-variable composite endpoint (EDSS, Timed 25-Foot Walk (T25FW), or Arm Function in Multiple Sclerosis Questionnaire (AMSQ)), and (3) a five-variable composite endpoint (EDSS, T25FW, AMSQ, Symbol Digit Modalities Test (SDMT), or Patient-Determined Disease Steps (PDDS)). Logistic regression modelled whether HADS scores predicted disability progression. Boruta feature selection identified the most informative HADS items.

RESULTS: One hundred eleven adults with PPMS completed the HADS (all ≥ 1-year follow-up; 62 ≥ 2 years). Progression occurred predominantly on individual domains. At 1 year, higher total HADS scores predicted progression on the five-variable composite endpoint (OR 3.10, [95% CI 0.99-9.75], p = 0.05; AUC 0.59, [95% CI 0.47-0.70]). At 2 years, the depression sub-score consistently predicted progression on EDSS (OR 8.88, [95% CI 1.12-70.66], p = 0.04), and the five-variable composite endpoint (OR 9.46, [95% CI 1.50-59.52], p = 0.02). Boruta feature selection identified HADS depression-associated items 6 and 8 as best predictors; together achieving similar predictive accuracy compared to the full HADS questionnaire.

CONCLUSION: Higher HADS scores, particularly depressive symptoms, predicted disability progression. These findings indicate prognostic value of patient-reported outcomes in predicting disease worsening and their potential use in guiding personalised treatment in progressive MS.