Screening for the Comorbidities That Accelerate MS Disability

Key Takeaways:

• Cerebrovascular disease, ischemic heart disease, anxiety, and depression are each associated with faster disability worsening in MS. All are treatable independently in ways the underlying disease is not.
• In the 2026 Multiple Sclerosis In America survey, 56.7 percent of respondents with relapsing forms reported anxiety and 47.2 percent reported depression in the past month.
• With 74.1 percent of respondents naming an MS specialist as their main provider, the neurology visit is where comorbidity screening happens or does not.

In the multiple sclerosis (MS) population, particularly in the older MS population, comorbidities can contribute to disability worsening. Comorbidities require different treatments than MS. Whether treating certain comorbidities changes the MS trajectory is still unknown – the evidence is associative, and the authors of the largest analysis say trials are needed to answer it – but these conditions are worth treating on their own terms regardless to prevent further disability

Comorbidity and disability trajectory

The more comorbidities an MS patient carries, the higher the risk of MS disease activity. In an analysis of 16,794 patients pooled from 17 phase 3 disease-modifying therapy trials, having 3 or more comorbidities was associated with increased evidence of disease activity (adjusted hazard ratio 1.14, 95 percent confidence interval 1.02 to 1.28). Having 2 or more cardiometabolic comorbidities raised the hazard ratio further to 1.21 (1.08 to 1.37). One or 2 comorbidities showed no association at all, which points to accumulation rather than to any single condition.¹

The effect on disability worsening is much larger than the effect on inflammatory activity. Cerebrovascular disease carried a hazard ratio of 3.20 (1.84 to 5.56) for disability worsening, ischemic heart disease 2.14 (1.21 to 3.81), and depression 1.29 (1.17 to 1.43). The authors are clear that this is association and not demonstrated causation, and note that comorbidity may be acting independently to contribute to disability and/or as a modifier of MS-mediated disability.¹

Vascular risk in older patients

The association between cardiovascular comorbidities and disability in MS is long-standing. In a registry cohort of 8,983 participants, each additional cardiovascular comorbidity carried a hazard ratio of 1.51 (1.41 to 1.61) for early gait disability. Patients with vascular comorbidity at diagnosis needed unilateral walking assistance a median of 12.8 years later, compared to 18.8 years for those without – 6 years earlier. Hypercholesterolemia, hypertension, diabetes, and peripheral vascular disease were each individually significantly associated with disability; heart disease alone was not.²

This matters because of the ageing MS population, in part as a result of the recent successes of high-efficacy disease-modifying therapies. In the 2026 In America survey, the mean age among respondents with relapsing forms of MS was 58.8 years, mean time since diagnosis was 19.9 years, and 48.2 percent held Medicare as their primary insurance.³ This shows that the majority of the MS population is in the age range where cardiovascular comorbidities are common and cardiovascular risk management is routine.

Psychiatric comorbidity and symptom attribution

Prevalence estimates for depression and anxiety in MS vary widely, but generally show that anxiety and depression are common in patients with MS. A systematic review of 118 studies reported population-based prevalence in MS patients of 23.7 percent (17.4 to 30.0) for depression and 21.9 percent (8.76 to 35.0) for anxiety. The authors attribute the spread to how cases were identified – structured interviews, administrative data, or any of more than 9 questionnaires – and to studies often not separating lifetime from current depression.⁴ Screening instruments return higher figures by design: a meta-analysis of 32 cross-sectional studies covering 15,853 patients found anxiety in 36 percent (30 to 42) using symptom-scale thresholds.⁵ In the 2026 Multiple Sclerosis In America survey, 56.7 percent of respondents with relapsing forms reported anxiety and 47.2 percent reported depression in the past month.³

Which figures are right matters less than noting that depression and anxiety are common in patients with MS. Depression is independently associated with disability worsening, is strongly associated with anxiety (odds ratio 7.89, 3.71 to 16.81), and it produces fatigue and cognitive symptoms independently.^1,5 While MS disease activity may contribute directly to increased risk of depression and anxiety, it is important to not just see depression and anxiety as an MS symptom. Depression and other mood disorders, regardless of their underlying cause, should be monitored for and treated in MS patients. This is especially important to limit compounding effects on disability and cognition.

Who screens for what

For most MS patients, the neurologist is the one clinician they see consistently and regularly. While fatigue and cognitive complaints are often monitored for and managed by the neurologist, deferring cardiovascular and mood disorder screening to a primary care provider that that patient may not see often (or at all) often means these screens will not happen.

A workable split is that neurology screens and defers to primary care for management as necessary. Screening can be quick – a mood questionnaire, blood pressure, and basic cardiovascular labs at the MS visit – and can help direct when the patient needs to follow up with primary care for management of mood disorders or cardiovascular risk factors. While general screening for comorbidities can be performed at regular neurology visits, treating what turns up is longitudinal work, and it belongs with primary care.