Background: Parkinson’s disease (PD) patients often experience non-motor symptoms like depression and anxiety, significantly impacting their quality of life. With the limited effectiveness of pharmacological treatments, effective non-pharmacological interventions are needed. This systematic review and meta-analysis aimed to evaluate the efficacy of cognitive-behavioral therapy (CBT) in reducing depression and anxiety symptoms in PD patients. Methods: Randomized controlled trials (RCTs) exploring CBT's effectiveness for depression and anxiety in PD patients were included. Studies published until April 2023 were identified from PubMed, Web of Science, and Scopus. Methodological quality was assessed using the Risk of Bias-2 (ROB-2) tool. Statistical analysis involved calculating the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) using Review Manager 5.4.1. Results: The systematic review included 12 studies involving 241 PD patients. CBT led to a substantial reduction in anxiety (SMD -0.95, 95% CI [-1.15 to -0.74], P < 0.00001) and depression (SMD -1.02, 95% CI [-1.39 to -0.65], P < 0.0001). Both traditional CBT and tele-CBT (administered over the phone or internet) were effective in treating depression and anxiety. Traditional CBT improved depression (SMD -1.16, 95% CI [-1.83 to -0.49], P < 0.00001), while tele-CBT showed comparable results (SMD -0.90, 95% CI [-1.31 to -0.48], P < 0.00001). For anxiety, both traditional CBT (SMD -0.94, 95% CI [-1.25 to -0.63], P < 0.00001) and tele-CBT (SMD -0.95, 95% CI [-1.22 to -0.67], P < 0.00001) significantly reduced symptoms. In conclusion, this systematic review and meta-analysis demonstrated the efficacy of CBT in reducing depression and anxiety in PD patients. Healthcare providers are encouraged to integrate CBT into their treatment protocols. However, additional high-quality studies with longer-term follow-up assessments are needed to further enhance understanding in this area. Prospero Registration: CRD42023424758.

Background: The management of Alzheimer's disease (AD) poses considerable challenges, necessitating the pursuit of innovative therapeutic approaches. Recent research has spotlighted the promising role of phosphodiesterase type 5 inhibitors (PDE5Is) in reducing the prevalence of AD, utilizing their vasodilatory properties to suggest a potential neuroprotective effect. This meta-analysis and systematic review aims to assess the relationship between the use of PDE5Is and the risk of AD. Methods: A detailed examination was carried out across several electronic databases till March 2024, including PubMed, Web of Science, Scopus, CENTRAL, and Embase. The focus was on identifying studies that compare the occurrence of AD among PDE5I users vs non-users. Through a random-effects model, pooled hazard ratios (HRs) were calculated, in alignment with guidelines from the Cochrane Handbook for Systematic Reviews and Meta-Analysis and the PRISMA standards. Results: This analysis included six studies, cumulating a participant count of 8,337,313, involving individuals treated with sildenafil, tadalafil, and vardenafil, against a control group undergoing other or no treatments. The cumulative HR for AD risk among PDE5I users versus the control group was 0.53 (95% CI: 0.32–0.86, p = 0.008), signaling a markedly reduced likelihood of AD development in the PDE5I group. Particularly, sildenafil usage showed a significant risk reduction (HR: 0.46, 95% CI: 0.31–0.70, p < 0.001), while findings for tadalafil and vardenafil were not significant. Test of subgroup differences found no difference between male and female participants in the risk of AD. Conclusions: Our findings suggest that the use of PDE5Is is associated with a reduced risk of AD, highlighting its potential as a protective agent against neurodegenerative diseases. Given the very low quality of evidence and the heterogeneity among the included studies, further high-quality research is warranted to confirm these findings and elucidate the underlying mechanisms. Register number PROSPERO 2024: CRD42024522197.

Migraine is a disabling disorder characterized by recurrent severe headache attacks. Non-invasive neuromodulation can be employed in the prevention and/or acute treatment of migraine. Remote electrical neuromodulation (REN), a type of non-invasive neuromodulation, is an effective and safe at-home treatment for migraine. It stimulates peripheral nerves in the upper arm to trigger conditioned pain modulation. We searched PubMed, Web of Science, Scopus, and the Cochrane Library for clinical trials and observational studies that assess the efficacy of REN in patients with migraine attacks. Statistical analysis was performed using Review Manager version 5.4.1 and Open Meta Analyst software. Our study included 12 studies with 9912 migraine patients. In the single-arm meta-analysis, 64% (95% CI: 0.62 to 0.65), and 22% (95% CI: 0.213 to 0.237) of patients experienced a reduction in pain and pain-free status at 2 h, respectively. Additionally, 59% (95% CI: 0.548 to 0.637), and 54% (95% CI: 0.471 to 0.609) of patients reported sustained pain relief and sustained pain-free status at 24 h, respectively. Marked functional improvement was achieved in 59% (95% CI: 0.577–0.607) of patients within 2 h post-treatment with REN, and 54.6% (95% CI: [0.519 to 0.574]) reported the disappearance of their most bothersome symptom (MBS). Device-related adverse events were reported in 0.4% (95% CI: 0.003 to 0.005) of patients. In double arm meta-analysis, pain-free status at 2 h had an odds ratio (OR) of 2.77 (95% CI: 1.63 to 4.71). While device-related adverse events had an OR of 1.45 (95%CI: 0.42 to 4.94). CRD42024596712