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

Background: 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).

Methods: 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.

Results: 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 < 0.001). At baseline, HLD patients had higher PST scores than non-HLD patients (β = 1.10, 95% CI 0.15 - 2.05, p = 0.022), but this difference did not remain over time. Individuals in the highest PST performance quartile were negatively impacted when diagnosed with depression, HTN, and DM relative to those without the comorbidities. There were no other correlations with PST scores and the remaining comorbidities. Depression was associated with lower baseline WBF (β = -0.0043, 95% CI -0.0084 - -0.0003, p = 0.033) and GMF (β = -0.0046, 95% CI -0.0078 - -0.0015, p = 0.004) along with larger T2LV (β = 0.1605, 95% CI 0.0082 - 0.3128, p = 0.039). HLD patients had more favorable baseline MRI measures, including higher WBF (β = 0.0076, 95% CI 0.0017 - 0.0135, p = 0.012) and TV (β = 0.0002, 95% CI 0.0000 - 0.0005, p = 0.041), with a lower T2LV (β = -0.2963, 95% CI -0.5219 - -0.0706, p = 0.010).

Conclusions: Comorbidities are common within a MS cohort and adversely impact processing speed. Depression adversely impacted PST scores with worse MRI outcomes. HLD was associated with lower longitudinal PST measures but favorable quantitative MRI metrics. MS patients with faster baseline processing speeds were most sensitive to comorbid conditions. Our findings suggest a complex interplay between cognition and comorbid conditions in MS patients.