In the context of neurodegenerative disorders, cognitive decline is frequently reported in older population. Recently, numerous metabolic pathways have been implicated in neurodegeneration, including signaling disruption of insulin and other glucose-regulating hormones. In fact, Alzheimer’s disease has now been considered as “type-3 diabetes”. In this review, we tried to clarify the role of sleep impairment as the third major player in the complex relationship between metabolic and neurodegenerative diseases. Altered sleep may trigger or perpetuate these vicious mechanisms, leading to the development of both dementia and type 2 diabetes mellitus. Finally, we analyzed these reciprocal interactions considering the emerging role of the gut microbiota in modulating the same processes. Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration. In a future prospective, gut microbiota could provide a major contribution in explaining the tangled relationship between sleep disorders, dementia and diabetes.

Background: Few studies compare the clinical effectiveness of the three anti-CGRP mAbs. Moreover, no studies compare their efficacy during suspension and reprisal. Our study aimed to compare the efficacy of migraine frequency, intensity, and symptomatic medication intake during the first year of therapy, a 1-month suspension period, and a 3-month drug reprisal. Methods: A total of 160 migraineurs (chronic and high-frequency episodic) were treated with anti-CGRP mAbs (49 with fremanezumab, 55 with erenumab, and 55 with galcanezumab) for 12 months. They discontinued the therapy for 1 month and then reprised the therapy. In the three groups, we analyzed and compared the migraine days per month, migraine intensity, and symptomatic medication intake per month at baseline, 3-month, 6-month, and 12-month follow-up. We also compared these variables during the 1-month suspension and 3 months after the reprisal of the therapy. We compared the data and evaluated the response rate (>50% reduction in migraine days per month) at different follow-ups. This comparison was also performed separately for chronic and high-frequency episodic migraineurs. Results: There was no statistical difference in monthly migraine days, intensity, or symptomatic medication intake per month at the different follow-ups. Moreover, there was no difference in the response rate overall. However, in chronic migraineurs treated with galcanezumab, the response rate was higher during the 1-month suspension when compared to fremanezumab and erenumab. In high-frequency episodic migraineurs, fremanezumab had a higher response rate at 12-month follow-up when compared to galcanezumab and erenumab. Conclusions: In our study, the three anti-CGRP mAbs presented a similar response, with no significant differences, during the first year of therapy, the suspension period, and 3 months after the drug reprisal. The response rate during the 1-month suspension period in chronic migraineurs may be higher with galcanezumab.

Multiple sclerosis is a chronic, autoimmune-mediated, demyelinating disease whose pathogenesis remains to be defined. In past years, in consideration of a constantly growing number of patients diagnosed with multiple sclerosis, the impacts of different environmental factors in the pathogenesis of the disease have been largely studied. Alterations in gut microbiome composition and intestinal barrier permeability have been suggested to play an essential role in the regulation of autoimmunity. Thus, increased efforts are being conducted to demonstrate the complex interplay between gut homeostasis and disease pathogenesis. Numerous results confirm that disease-modifying therapies (DMTs) used for the treatment of MS, in addition to their immunomodulatory effect, could exert an impact on the intestinal microbiota, contributing to the modulation of the immune response itself. However, to date, the direct influence of these treatments on the microbiota is still unclear. This review intends to underline the impact of DMTs on the complex system of the microbiota–gut–brain axis in patients with multiple sclerosis.