Background: Parkinson's disease (PD) is characterized by proteinopathies and these proteinopathies seem to interact synergistically and lead to protein aggregations and changes in protein cerebrospinal fluid (CSF) levels. In this study, we aimed to explore the longitudinal changes of CSF a lpha-synuclein (α-syn), total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (Aβ1−42) and their relationships with each other and with baseline clinical entities like REM sleep behavior disorder (RBD), cognitive impairment, motor symptoms, and olfaction dysfunction.Method: One hundred and twelve non-demented PD patients and 110 controls were recruited from Parkinson's Progression Markers Initiative (PPMI).We used a linear mixed model within groups to assess longitudinal protein changes over 6 and 12 months and a random regression coefficient within the linear mixed model to investigate the correlation between proteins and their baseline clinical characteristics.Results: P-tau was lower in PDs only at baseline, but during a year, p-tau increased more rapidly in PDs than controls. Aβ1−42 was not significantly different between groups at any separate timepoint; however, when assessed longitudinally, Aβ1−42 showed significant changes in both groups. Conversely, t-tau and α-syn differed significantly between groups, but their longitudinal changes were not significant in either of the groups. Moreover, all proteins' baseline levels, except p-tau, could determine estimated longitudinal tau changes. Baseline RBDSQ scores but not UPDRS III, MoCA, or UPSIT scores were predictive of longitudinal increase in α-syn levels.Conclusion: Longitudinal changes in levels of CSF proteins are related to each other and could help researchers further understand PD pathology. In addition, RBD seems to be a potential prognostic factor for PD progression. However, in order to reach a consensus, longer follow-up times are required.

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Objective: Major depressive disorder (MDD) is predicted to be the first cause of burden of disease. The antidepressant activity of gemfibrozil has been recently considered. This study was designed to evaluate the effectiveness of gemfibrozil as a sertraline adjunct in treating patients with MDD. Method: A total of 46 patients with MDD based on the DSM-V criteria with a minimum score of 22 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomized to receive either 300 mg daily gemfibrozil or placebo in addition to 100 mg sertraline for 8 weeks in a randomized, double-blind placebo-controlled trial. Patients were evaluated for response to treatment using the HAM-D score at baseline and weeks 2, 4, and 8. Results: Forty-five patients completed the study and took part in all follow-up visits. Repeated measure ANOVA with a Greenhouse-Geisser correction showed a significant difference for time×treatment interaction on within-subjects HAM-D scores [p–value= 0.026]. A significant difference was seen in time [p–value < 0.001]. The test of between-subject effects also showed a significant effect of treatment on HAM-D scores at weeks 2, 4, and 8 [p–value = 0.07]. Using KaplanMeier estimate curves, time to remission periods were significantly different between the 2 trial arms [Log-Rank p–value = 0.003]. Conclusion: Gemfibrozil is an effective adjunctive treatment in MDD and can be used to reduce depression symptoms.

Objective. In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). Background. JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. Methods. Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Results. Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947–0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). Conclusions. In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.