RESUMO
Background: Impaired glucose and energy metabolism has been suggested as a pathogenic mechanism underlying Parkinson's disease (PD). In recent cohorts, phosphoglycerate kinase 1 activators (PGK1a) have been associated with a lower incidence of PD when compared with other antiprostatic agents that do not activate PGK1. Objective: We aimed to perform a systematic review and meta-analysis comparing the incidence of PD in patients taking PGK1a versus tamsulosin. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PGK1a vs. tamsulosin in adults and elderly. The primary outcome was the incidence of PD. We computed hazard ratios (HR) for binary endpoints, with 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager 5.4 and R (version 4.3.1). Results: A total of 678,433 participants from four cohort studies were included, of whom 287,080 (42.3%) received PGK1a. Mean age ranged from 62 to 74.7 years and nearly all patients were male. Patients taking PGK1a had a lower incidence of PD (PGK1a 1.04% vs. tamsulosin 1.31%; HR 0.80; 95% CI 0.71-0.90; pâ<â0.01). This result remained consistent in a sensitivity analysis excluding patients of age 60 years old or younger (PGK1a 1.21% vs. tamsulosin 1.42%; HR 0.82; 95% CI 0.71-0.95; pâ<â0.01). Conclusions: Glycolysis-enhancing drugs are associated with a lower incidence of PD when compared with tamsulosin in adults and elderly individuals with prostatic disease in use of alpha-blockers. Our findings support the notion of glycolysis as a potential neuroprotective mechanism in PD. Future investigations with randomized controlled trials are needed.
It has been suggested that impairment in glucose and energy metabolism is one of the mechanisms underlying the development of Parkinson's disease. In recent studies, medications traditionally prescribed for prostate diseases, called phosphoglycerate kinase 1 activators (PGK1a), have been associated with a lower incidence of Parkinson's disease when compared to other medications for the same purpose that do not activate the same energetic pathway. Therefore, we thoroughly reviewed the literature and combined the results of studies that compared both medications (PGK1a versus another medicationâ thatâ does not activate this energetic pathway, called tamsulosin), evaluating the incidence of Parkinson's disease in both groups. We included a total of 678,433 individuals, of whom 42.3% received PGK1a and 57.7% received tamsulosin. In our analysis, patients taking PGK1a had a lower incidence of Parkinson's disease when compared to the other group, even when we excluded patients younger than 60 years of age. As a result, our findings support the notion that the increase of energy metabolism is a potential neuroprotective mechanism in Parkinson's disease and future investigations are needed.
Assuntos
Doença de Parkinson , Fosfoglicerato Quinase , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Glicólise/efeitos dos fármacos , Incidência , Doença de Parkinson/epidemiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/prevenção & controle , Fosfoglicerato Quinase/metabolismo , Tansulosina/administração & dosagem , FemininoRESUMO
Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression - Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.Prospero registry: CRD42023486694.