Background: Adverse childhood experiences (ACEs) refer to distressing events before age 18 that can lead to potential mental and physical health consequences. This systematic review and meta-analysis aimed to examine the association between ACEs and the risk of dementia in elderly adults who experienced ACEs during childhood, addressing the existing inconsistencies and methodological variations. Methods: A comprehensive search strategy was employed across key databases (PubMed, Web of Science, Scopus, and Embase) to identify relevant articles. Our primary outcome was ACEs-dementia risk, and our secondary outcome was mild cognitive impairment risk. A quality assessment was conducted using the Newcastle–Ottawa Quality Assessment Scale and GRADE. A random-effects model was utilized to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed to explore potential sources of heterogeneity and assess the reliability of the results. Results: Out of 1,376 screened papers, nine studies were included. The studies consisted of two case-control, one prospective cohort, and six retrospective cohort studies conducted in the UK, France, USA, China, and Spain. Five studies were of good methodological quality according to the NOS. according to the GRADE, all outcomes were classified as very low or low quality of evidence. A significant association was observed between ACEs and dementia risk (OR = 1.35; 95% CI 1.20, 1.52; P = 0.00001) and mild cognitive impairment risk (OR = 1.28; 95% CI 0.63, 2.62; P = 0.49). A meta-analysis by type of adversity revealed significant results for the maltreatment subgroup(OR = 1.30; 95% CI 0.07-1.58; P = 0.007; I² = 0%). Subgroup analysis based on the dementia definition revealed no between-subgroup difference (P = 0.71) between tool-based and register/criteria-based subgroups. No possibility of Publication bias was observed upon inspection of the funnel plot. Conclusion: Adverse childhood experiences may be associated with an increased risk of dementia. However, caution is warranted in interpreting these results due to the limited number of studies. Larger high-quality studies investigating the association between ACEs and dementia risk are needed to confirm the reliability of our results.

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: Statins or 3‑hydroxy‑3‑methyl‑glutarylcoenzyme A (HMG‑CoA) reductase inhibitors are medications that act by reducing the cholesterol content of liver cells Moreover, statins have been found to improve endothelial function and reduce vascular wall inflammation. A growing body of research suggests that statins are associated with less risk of migraine, and they can be used to treat symptoms. However, the evidence has been inconclusive, so we aim to investigate the nature and strength of the effect of statins on the prevention and prophylaxis of migraines. Methods: We conducted a comprehensive systematic search across multiple electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, from inception until October 2024, to include studies on the association between statins use and migraine. The outcomes of interest involved the association of the HMG-CoA reductase gene with the risk of migraine, as well as the association and efficacy of statins in migraine patients. Results: Thirteen studies were included in our systematic review. Mendelian Randomization (MR) studies revealed that expression of HMGCR was associated with an increased risk of migraine with odds ratio (OR) ranging from 1.38 to 1.55 (P < 0.001). Three observational studies investigating the relationship between statins and migraine risk demonstrated a protective effect, with odds ratios ranging from 0.73 to 0.94 (P < 0.001). The findings suggest a significant reduction in overall migraine risk, particularly for migraines with aura and in patients with higher vitamin D levels. Meta-analysis of randomized controlled trials (RCTs) showed that statins significantly reduced monthly migraine frequency (MD= -3.16, 95%CI= [-5.79, -0.53]; p = 0.02, I2 = 79%; P = 0.03). RCTs supported the efficacy of statins in reducing migraine frequency, days, and intensity compared to placebo. Conclusions: Statins, already well-established for cardiovascular benefits, emerge as a promising dual-purpose therapy for many neurological disorders. The association between the HMGCR gene and increased migraine risk, coupled with the possible efficacy of statins in reducing migraine frequency, may open new avenues for migraine prophylaxis. However, the variability in study design hinders definitive conclusions, so larger studies with longer follow-ups are required to ascertain both findings.

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.