Vascular comorbidity is associated with lower brain volumes and lower neuroperformance in a large multiple sclerosis cohort

Abstract

Objective: The objective of this study is to assess the association between vascular comorbidity burden with clinical and imaging features of disease burden in a large population of people with multiple sclerosis (MS).

Methods: We included participants from the MS Partners Advancing Technology Health Solutions (MS PATHS) cohort. We evaluated if vascular comorbidities (diabetes, hypertension, and dyslipidemia) or a composite sum of comorbidities was associated with MS characteristics, including objective neurologic function assessments and quantitative brain magnetic resonance imaging (MRI) measurements in propensity score-weighted models.

Results: In total, 11,506 participants (6409 (55%) with brain MRI) were included. Individuals with 2+ vascular comorbidities had slower walking speed (standard deviation (SD) = -0.49; 95% confidence interval (CI) = -0.78, -0.19; p = 0.001), slower manual dexterity (SD = -0.41; 95% CI = -0.57, -0.26; p < 0.0001), and fewer correct scores on cognitive processing speed (SD = -0.11; 95% CI = -0.20, -0.02; p = 0.02) versus those with no comorbidities. Those with 2+ had lower brain parenchymal (-0.41%, 95% CI = -0.64, -0.17) and gray matter fractions (-0.30%, 95% CI = -0.49, -0.10), including reduced cortical (-10.10 mL, 95% CI = -15.42, -4.78) and deep (-0.44 mL, 95% CI = -0.84, -0.04) gray matter volumes versus those with no comorbidity.

Conclusion: Increased vascular comorbidity burden was associated with clinical and imaging markers of neurologic dysfunction and neurodegeneration in MS. Strategies to optimize comorbidity management in people with MS are warranted.

Keywords: Comorbidity; epidemiology; metabolic disorders.

Figure 1:. Vascular comorbidity burden and Z-scored neuroperformance tests.

Z-scores were calculated from regression-based equations derived from a healthy volunteer study of individuals aged 18 to 89 (n=517) of MSPT outcomes. The mean for each neuroperformance outcome is equal to 0 and the standard deviation is equal to 1 among the healthy controls. Thus, values presented denote a per SD difference in a given outcome. All values are derived using propensity score weighted models. Individuals with 2+ comorbidities had −0.49 SD slower (95% CI: −0.78, −0.19) walking speed, −0.41 SD (95% CI: −0.57, −0.26) lower manual dexterity speed, and −0.11 SD (−0.20, −0.02) lower Z-scored processing speed. We detected a significant trend across comorbidity burden for differences in walking speed (p=0.002), manual dexterity (p<0.0001), but not for processing speed (p=0.13). P for trend denotes the p-value derived from a test of linear trend across number of comorbidities in which the number of comorbidities was modeled as a continuous covariate.

Figure 2:. Vascular comorbidity burden and neuroimaging Z-scores

Values are transformed to Z-scores (with mean = 0 and standard deviation = 1) in people with MS so that all are displayed on the same scale and with the same directionality. Values presented denote a per SD difference in a given outcome. All values are derived using propensity score weighted models. We detected a significant trend across comorbidity burden for differences in BPF (p=0.0007), GMF (p=0.0007), and cortical GM (p=0.002), but not for deep GM (p=0.16) or thalamic volume (p=0.93) P for trend denotes the p-value derived from a test of linear trend across number of comorbidities in which the number of comorbidities was modeled as a continuous covariate.