Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Association between cognitive impairment and the disability in people with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) may be present in people with multiple sclerosis (PwMS) in different stages of the disease, as well as in PwMS with various degrees of disability. This study aimed to investigate cognitive decline over a period of 12 months and to examine an association between cognition and the disability in PwMS, also over a period of 12 months. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used, containing the Symbol Digit Modalities Test (SDMT), the Categorical Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test-Revised (BVMT-R). The Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9-HPT) were used to assess the degree of disability. For the analysis of cognitive decline over the period of 12 months, Wilcoxon signed-rank test (paired sample t-test) was used. For the correlation between cognition and disability, Spearman's correlation test was used. RESULTS: We observed statistically meaningful difference only in one measure of cognition (CVLT), not the other two (SDMT and BVMT-R). SDMT significantly correlated with methods assessing the degree of disability in both time points. In the second examination, we observed a correlation between BICAMS and 9-HPT. Similarly, SDMT and BVMT-R also correlated with EDSS. CONCLUSION: To investigate the cognitive decline in PwMS, a longer period of time probably should have been chosen. EDSS is commonly used to monitor disease progression, but it does not include the evaluation of various parameters, such as cognition or upper limb function. Its use with the 9-HPT and cognitive tests may represent a more reliable and comprehensive assessment of a patient's clinical condition.

Cognition in Patients with Sleep-Disordered Breathing: Can Obstructive and Central Apneic Pauses Play a Different Role in Cognitive Impairment?

BACKGROUND: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment. METHODS: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke's Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains. RESULTS: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009-1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004-1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains. CONCLUSION: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.