Vascular co-morbidities, race, and executive function in multiple sclerosis

Abstract

Multiple Sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by cerebrovascular alterations, neuroinflammation, leukocyte extravasation, demyelination, axonal damage, and neurodegeneration. MS is associated with increased vascular risk factors (VRFs) in number and severity, which are even prevalent at MS symptom onset and are associated with greater impairments in neuronal integrity and CBF reductions, accelerated disease and disability progression, greater cognitive dysfunction, higher mortality rates, and reduced quality of life. Moreover, MS and VRFs have essentially identical pathophysiology, and therefore, their cooccurrence likely manifests in a vicious neuroinflammatory/neurodegenerative feed-forward cycle which culminates in more severe disease and worse outcomes. ¶ Black people with MS (BpwMS) in particular demonstrate a propensity for more aggressive disease, with greater disability and executive dysfunction as compared to their White counterparts. This phenomenon may be related to the increased incidence of VRFs among Bp, which also tend to be more severe, occur at younger ages, and are associated with increased mortality. These susceptibilities may be related to their predisposition for comparatively greater reductions in cerebrovascular reactivity and neurovascular dysfunction, which are even observed among young and otherwise healthy Bp. Notable, however, only one study has investigated racial disparities in VRFs in MS, and it has yet to be investigated if VRFs account for racial disparities in executive dysfunction in MS. Accordingly, the primary aims of this study were to investigate 1) if racial differences in executive dysfunction among participants in this sample are similar to those observed in previous studies, 2) if VRFs are associated with executive dysfunction, and 3) if the association between the prevalence of vascular risk factors and executive dysfunction is moderated by race. The first two aims were evaluated using a multiple linear regression model of race and vascular risk index adjusting for each other and predicting each executive functioning variable separately; the third aim added in the interaction term of races and vascular risk index to each model for each executive functioning variable. ¶ This study employed a retrospective cross-sectional design with a sample of 74 participants; 66.2% were White and 33.8% were Black. Black participants were diagnosed significantly more recently than White participants by 4.56 years (disease duration: t(72) = 2.28, p = .025). There were no other significant demographic differences in other demographics, including vascular risk factors. Notably, however, 58.1% of the sample had a BMI > 25, 8.1% had type II diabetes, 25.7% had hypertension, 6.8% had hypercholesteremia, and 1.4% had coronary artery disease.¶ Participants were administered the California Verbal Learning Test-II (CVLT-II), 3-second version of the Paced Auditory Serial Addition Test 3” (PASAT), Symbol Digit Modalities Test (SDMT), Wisconsin Card Sorting Test (WCST), and the Controlled Oral Word Association Test (COWAT). On the SDMT, unemployed participants (M = -1.46, SD = 1.35) scored significantly lower than employed participants (M = -.72, SD = 1.32; t(72) = -2.38, p = .020). Similarly, on the COWAT, unemployed participants (M = -1.01, SD = 1.31) scored significantly lower than employed participants (M = -.26, SD = 1.29; t(72) = -2.45, p = .017). Age was significantly, and positively correlated with performance on the COWAT, r(72) = .24, p = .038. Performance across all executive function measures fell below standardized means, and there was a high rate of impairment across all measures except for CVLT-II Retroactive Interference in the overall sample. Black participants had significantly lower scores than White participants on the PASAT (M = -2.16, SD = 1.35 versus M = -1.30, SD = 1.38) and WCST Perseverative Errors (M = 40.3, SD = 10.4 versus M = 46.7, SD = 11.0). In the multiple regression analysis, race and vascular risk, together, accounted for 13.3%, 6.3%, 0.3%, 8.1%, 0.6%, 3.1% of the variability on the PASAT, SDMT, CVLT-II Retroactive Interference, WSCT Perseverative Errors, WCST Total Trials Administered and COWAT scores, respectively. The effect of vascular risk index on executive function was not race-dependent. Interpretation of these results, conclusions, clinical implications, and future directions are discussed herein.