Comorbidity effect on processing speed test and MRI measures in multiple sclerosis patients

•Comorbidities worsen clinical outcomes in patients with multiple sclerosis (MS).•Multiple comorbidities resulted in slower processing speed.•Depression impairs processing speed and worsens MRI outcomes.•Complex relationship between cognitive outcomes and comorbid conditions MS. Comorbid conditions are known to affect the clinical course of multiple sclerosis (MS). Our objective was to determine the impact of comorbidities on the processing speed test (PST). We conducted a retrospective, longitudinal analysis of all patients who completed PST testing from June 2015 - August 2019 at our center. Our electronic medical record was queried to determine the presence of the following comorbidities: diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), coronary artery disease, and depression. To help address baseline PST performance and practice effect, patients were also divided into four quartiles by baseline PST scores. Brain MRIs obtained within a 90-day window from the initial clinical assessment were quantitatively analyzed via fully-automated methods to calculate whole brain fraction (WBF), T2 lesion volume (T2LV), gray matter fraction (GMF), and thalamic volume (TV). Univariable and multivariable linear regression models were used to determine the relationship between the comorbidities, PST performance and MRI metrics over time. A total of 4,344 patients (mean age 49.5 ± 12.4 years, 72.3% female, and 63.7% relapsing remitting MS) were included in the analysis with 13,375 individual patient encounters. Over half the cohort (52.4%) suffered from at least one comorbidity with the most common being depression (37.4%), HLD (20.9%), HTN (19.6%), and DM (6.4%). Patients with one or more comorbidity had lower baseline PST scores. Longitudinally, patients with two comorbidities lost 1.46 points on the PST per year relative to those with no comorbidities (95% CI -2.46 – -0.46, p = 0.004). Individuals with depression had lower PST scores than those without, and this difference persisted over time (β = -2.40, 95% CI -3.08 – -1.73, p