Dyskinesia is one of the most disabling motor complications in Parkinson’s Disease (PD). Sleep is crucial to keep neural circuit homeostasis, and PD patients often suffer from sleep disturbance. However, few prospective studies have been conducted to investigate the association of sleep quality with dyskinesia in PD. The objective of the current study is to investigate the association between sleep quality and dyskinesia and build a prediction model for dyskinesia in PD. We prospectively followed a group of PD patients without dyskinesia at baseline for a maximum of 36 months. Univariable and multivariable Cox regression with stepwise variable selection was used to investigate risk factors for dyskinesia. The performance of the model was assessed by the time-dependent area under the receiver-operating characteristic curve (AUC). At the end of follow-up, 32.8% of patients developed dyskinesia. Patients with bad sleep quality had a significantly higher proportion of dyskinesia compared with those with good sleep quality (48.1% vs. 20.6%, p = 0.023). Multivariable Cox regression selected duration of PD, sleep quality, cognition, mood, and levodopa dose. Notably, high Pittsburgh sleep quality index (PSQI) score was independently associated with an increased risk of dyskinesia (HR = 2.96, 95% CI 1.05–8.35, p = 0.041). The model achieved a good discriminative ability, with the highest AUC being 0.83 at 35 months. Our results indicated that high PSQI score may increase the risk of developing dyskinesia in PD, implying that therapeutic intervention targeting improving sleep quality may be a promising approach to prevent or delay the development of dyskinesia in PD.

The prevalence of Alzheimer’s disease (AD) has been increasing continuously, representing a major issue for public welfare. Detecting cognitive impairment due to AD at its early stages is an urgent prerequisite for therapeutic treatment to slow or halt disease progression before major brain damage occurs. Event-related potentials (ERPs) are a noninvasive neurophysiological technique with the advantages of objectivity, ease of operation, and real-time reflection of cognitive processing in the brain. The purpose of this paper is to comprehensively assess the application value of ERP in AD. By systematically searching relevant literature in PubMed, Web of Science and Scopus databases, and merging and analyzing the literature included in the study, we explored the roles of various components of ERP in the diagnosis, disease monitoring and pathological mechanism research of AD, and provided a comprehensive overview of the current status and prospect of the application of ERP in AD.

Background: Non-invasive neuroregulation techniques have been demonstrated to improve certain motor symptoms in Parkinson’s disease (PD). However, the currently employed regulatory techniques primarily concentrate on stimulating single target points, neglecting the functional regulation of networks and circuits. The supplementary motor area (SMA) has a significant value in motor control, and its functionality is often impaired in patients with PD. The matching SMA-primary motor cortex (M1) paired transcranial magnetic stimulation (TMS) treatment protocol, which benefits patients by modulating the sequential and functional connections between the SMA and M1, was elucidated in this study.Methods: This was a single-center, double-blind, randomized controlled clinical trial. We recruited 78 subjects and allocated them in a 1:1 ratio by stratified randomization into the paired stimulation (n = 39) and conventional stimulation groups (n = 39). Each patient underwent 3 weeks of matching SMA-M1 paired TMS or sham-paired stimulation. The subjects were evaluated before treatment initiation, 3 weeks into the intervention, and 3 months after the cessation of therapy. The primary outcome measure in this study was the Unified Parkinson’s Disease Rating Scale III, and the secondary outcome measures included non-motor functional assessment, quality of life (Parkinson’s Disease Questionnaire-39), and objective assessments (electromyography and functional near-infrared spectroscopy).Discussion: Clinical protocols aimed at single targets using non-invasive neuroregulation techniques often improve only one function. Emphasizing the circuit and network regulation in PD is important for enhancing the effectiveness of TMS rehabilitation. Pairing the regulation of cortical circuits may be a potential treatment method for PD. As a crucial node in motor control, the SMA has direct fiber connections with basal ganglia circuits and complex fiber connections with M1, which are responsible for motor execution. SMA regulation may indirectly regulate the function of basal ganglia circuits. Therefore, the developed cortical pairing stimulation pattern can reshape the control of information flow from the SMA to M1. The novel neuroregulation model designed for this study is based on the circuit mechanisms of PD and previous research results, with a scientific foundation and the potential to be a means of neuroregulation for PD.Clinical trial registration: ClinicalTrials.gov, identifier [ChiCTR2400083325].

Purpose: Impulse control disorders (ICDs) and excessive daytime sleepiness (EDS) are common symptoms in Parkinson’s disease (PD). Few longitudinal studies have focused on the association between EDS and ICDs. This longitudinal study aimed at assessing association between EDS and ICDs in PD. Patients and Methods: Patients without ICDs were incorporated from the Parkinson’s Progression Markers Initiative. All patients were followed until the onset of ICDs or the end of 4 years. A total of 260 PD patients were included. Univariable and multivariable logistic regression were used to explore association between EDS and ICDs. Results: The overall frequency of ICDs at the end of follow-up was 23.8% (62 patients). The mean duration from dopamine replacement therapy to develop ICDs was 3.30 ± 2.42 years. Patients with ICDs had significantly higher Epworth Sleepiness Scale (ESS) score (P = 0.002) and higher proportion of EDS (P = 0.030) when compared to patients without ICDs. The multivariable logistic regression analysis indicated that high ESS (OR = 2.01, 95% CI 1.01– 4.04, p = 0.049) score, high dopamine agonist equivalent daily dose (OR = 2.54, 95% CI 1.37– 4.71, p = 0.003), high Geriatric Depression Scale (OR = 2.33, 95% CI 1.27– 4.28, p = 0.006) score and postural instability (OR = 3.03, 95% CI 1.26– 7.29, p = 0.013) were associated with ICDs occurrence. Conclusion: Our results indicated that EDS acts as a risk for ICDs occurrence in PD. Clinicians should pay attention to EDS in clinical practice. This may be a promising new approach to better understand and therapy ICDs.

Depression, as an important prodromal non-motor manifestation of Parkinson’s disease (PD), its early predictive indicators remain unclear. Although cross-sectional studies suggest an association between serum uric acid (UA) levels and depression in PD, longitudinal evidence in the prodromal period is lacking. This study innovatively conducted a 5-year longitudinal study in a population with prodromal Parkinson’s disease (pPD), revealing for the first time the longitudinal association between serum UA levels and the development of depression. At baseline, we selected 460 pPD patients from the Parkinson’s Progression Markers Initiative (PPMI) database. Eventually, 61 participants completed a 5-year longitudinal study with annual assessments. Predictor variables were selected through univariate Cox analysis and LASSO regression, with multivariate Cox regression models employed to assess the independent association between serum UA levels and incident depression in the pPD cohort. At baseline, 18.9 % of pPD patients developed depression, and the cumulative incidence rates of depression during the 5-year follow-up period were 34.43 %, 49.18 %, 57.38 %, 62.30 % and 63.93 %, respectively. Multivariate Cox regression analysis, adjusted for covariates including sex and age, identified a higher Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part I (MDS-UPDRS I) score (HR = 1.177, 95 % CI 1.093–1.267, P < 0.001) and lower serum UA levels (HR = 0.776, 95 % CI 0.619–0.974, P = 0.029) as independent risk factors for incident depression in the pPD cohort. Our study shows that lower serum UA levels can independently predict the risk of depression in pPD, providing a new biomarker for the early identification of high-risk populations.

Objective: Subsyndromal symptomatic depression (SSD) is associated with an increased risk of cognitive impairment in non-demented older adults. However, the mechanism underlying this relationship remains unclear. This study aimed to investigate whether plasma neurofilament light chain (NfL) mediates the relationship between SSD and cognitive decline.Materials and methods: Data of 707 non-demented older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort were analyzed. Geriatric Depression Scale (GDS) scores were collected at baseline, while plasma NfL levels and cognitive assessments were obtained at baseline, 1-year, and 2-year follow-up visits. SSD was defined as a GDS score of 1–5. Mediation analyses were performed to examine whether the rate of change in plasma NfL levels mediated the relationship between SSD and cognitive decline.Results: Participants with SSD exhibited a greater increase in plasma NfL levels and more pronounced declines in global cognition, memory, executive function, language, and processing speed over 2 years compared to non-SSD participants. The rate of change in plasma NfL levels significantly mediated the relationship between SSD and accelerated cognitive decline, particularly in global cognition, memory, language, and processing speed.Conclusion: Plasma NfL, which is related to neuroaxonal damage, may partially mediate the association between SSD and accelerated cognitive decline in non-demented older adults. These findings suggest that dynamic changes in plasma NfL levels may reflect early neurobiological alterations associated with SSD and could help identify individuals at increased risk of cognitive deterioration over a 2-year period.