BACKGROUND:Freezing of gait (FOG), a debilitating axial symptom of Parkinson's disease (PD), lacks objective detection methods. While antisaccade (AS) latency prolongation correlates with FOG, the more complex memory-guided saccade (MGS), which requires multistage motor sequence integration (a proposed FOG mechanism), remains unexplored in FOG. METHODS:We assessed prosaccade (PS), AS, and MGS via infrared eye tracking in 75 PD patients (25 with FOG [PD-FOG], 50 without FOG [PD-nFOG]) and 75 healthy controls (HCs). The clinical assessments included the MDS-UPDRS III, the NFOG-Q, and cognitive/affective scales. Group differences were analyzed using appropriate comparative tests. Spearman's rank correlation was employed to examine associations between the saccade metrics and demographics/clinical features. Multivariate logistic regression was used to identify saccade metrics and demographics/clinical features associated with FOG. RESULTS:Compared to PD-nFOG patients and HCs, PD-FOG patients presented significantly prolonged MGS latency (p < 0.001) but not PS or AS latency. MGS latency showed the strongest correlation with axial symptoms [ρ = 0.494, p (FDR) < 0.01], remaining significant after adjusting for confounders (ρ = 0.262, p = 0.026). Multivariate logistic regression identified MGS latency [OR per SD increase = 4.814, 95 % CI: 1.457-15.910, p (FDR) = 0.044] and axial subscore [OR = 1.711, 95 % CI: 1.129-2.592, p (FDR) = 0.044] is associated with FOG. The MGS latency distinguished PD-FOG patients from PD-nFOG patients with high accuracy (AUC = 0.840, 95 % CI: 0.738-0.942; sensitivity/specificity = 84 % at the 407.5 ms cutoff). MGS latency was also correlated with NFOG-Q score in PD-FOG patients (ρ = 0.423, p = 0.035). CONCLUSIONS:Prolonged MGS latency is an independent indicator associated with axial symptoms and FOG in PD patients, suggesting that saccade represents a promising noninvasive approach for indirect identification of FOG and reflection of its severity.

BACKGROUND:The choroid plexus (CP), an important structure involved in cerebrospinal fluid (CSF) circulation, plays a key role in clearing harmful metabolites from the brain. However, the relationship between CP and the development of Parkinson's disease (PD) remains unclear, especially in those with freezing of gait (FOG). We aim to investigate the association between the CP area and CP/lateral ventricle area (CP/Ven) index with clinical symptoms of PD and the development of FOG. METHODS:Seventy-three patients with PD (17 with FOG and 56 without FOG) and 49 healthy controls (HCs) underwent 7 T magnetic resonance imaging and neurological assessments. The CP area and CP/Ven index were calculated, and the differences across groups were compared. Spearman's rank correlation was used to evaluate associations between these indices and clinical scales. Binary logistic regression was used to explore the impact of the CP area and CP/Ven index on FOG occurrence in PD. RESULTS:Patients with FOG (PD-FOG) exhibited significantly higher CP area and CP/Ven index than those without FOG (PD-nFOG). Both the CP area and CP/Ven index were positively correlated with the PD motor scale scores, especially postural instability/gait disturbance. Receiver operating characteristic curve analysis showed that the CP area and CP/Ven index effectively distinguished PD-FOG from PD-nFOG, with area under curve of 0.887 and 0.854, respectively. Logistic regression analysis confirmed that both indices independently increased the risk of FOG in PD. CONCLUSION:Elevated CP area and CP/Ven index are novel, noninvasive neuroimaging markers of FOG in PD.

Parkinson’s disease (PD) is a common neurodegenerative disorder, and neuroinflammation plays a pivotal role in its pathogenesis. T-cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) is a crucial immunoregulatory mediator in various diseases; however, its roles and underlying molecular mechanisms in PD remain unclear. We established in vitro and in vivo 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models in Tim-3–knockout BV2 cells and mice, respectively. Motor function was assessed through behavioral tests, including pole, traction, forced swimming, and open field tests. Immunofluorescence was used to examine dopaminergic neuron loss and glial activation. The expression levels of nuclear factor-kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) pathway components were evaluated by western blotting. Proinflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Compared with the wild-type, Tim-3 expression was significantly increased in the PD model, and Tim-3 deficiency mitigated MPTP-induced motor deficits, dopaminergic neuron loss, and glial cell activation. Furthermore, Tim-3 deficiency suppressed neuroinflammation by negatively modulating the NF-κB/NLRP3 pathway, thereby downregulating the expression of the proinflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α. These findings indicate that Tim-3 plays a proinflammatory role in PD by regulating the NF-κB/NLRP3 pathway, highlighting Tim-3 as a promising therapeutic target for PD.

Previous studies have yielded inconsistent results regarding the association between chronic kidney disease (CKD) and the risk of cognitive impairment (CI). This study aimed to investigate the longitudinal association of CKD with CI risk in the Chinese middle-aged and older population. A total of 16,515 CI-free participants 45 years of age or older including 15,595 without CKD and 920 with CKD were followed from 2011 until 2018 (median [interquartile range]: 7 [5.5-7]) to detect incident CI. Over the follow-up, 648 participants developed CI. Data were analyzed using multi-adjusted Cox proportional hazard regression and Laplace regression. The incidence rate (IR) of CI was significantly higher in individuals with CKD at 11.46 per 1,000 person-years (95% confidence interval [CI], 8.90 to 14.76) than in those without CKD at 6.38 per 1,000 person-years (95% CI, 5.89 to 6.92). Compared to those without CKD, the hazard ratios of those with CKD was 1.56 (95% CI, 1.19 to 2.04) for CI. Participants with CKD in the middle-aged group (45-54 years) exhibited a heightened risk of CI in age-stratified analyses. CKD accelerated the onset of CI by 1.24 years (10th percentile difference [PD]; 95% CI, -2.03 to -0.43, p < 0.01). The findings from this study revealed a significantly increased risk of CI in individuals with CKD, especially in middle-aged population, where the risk appeared to be more pronounced. This observation underscores the importance of early detection and intervention strategies to alleviate the potential cognitive decline associated with CKD.

BackgroundPrevious epidemiological studies have reported an association between Sjögren’s syndrome (SS) and Parkinson’s disease (PD); however, the causality and direction of this relationship remain unclear. In this study, we aimed to investigate the causal relationship between genetically determined SS and the risk of PD using bidirectional Mendelian randomization (MR).MethodsSummary statistics for Sjögren’s syndrome used as exposure were obtained from the FinnGen database, comprising 1,290 cases and 213,145 controls. The outcome dataset for PD was derived from the United Kingdom Biobank database, including 6,998 cases and 415,466 controls. Various MR methods, such as inverse variance weighted (IVW), Mendelian randomization Egger regression (MR-Egger), weighted median (WM), simple mode, weighted mode, MR-pleiotropy residual sum and outlier (MR-PRESSO), and robust adjusted profile score (RAPS), were employed to investigate the causal effects of SS on PD. Instrumental variable strength evaluation and sensitivity analyses were conducted to ensure the reliability of the results. In addition, reverse MR analysis was performed to examine the causal effects of PD on SS.ResultsThe WM, IVW, RAPS and MR-PRESSO methods demonstrated a significant association between genetically predicted SS and reduced risk of PD (odds ratio ORWM = 0.9988, ORIVW = 0.9987, ORRAPS = 0.9987, ORMR-PRESSO = 0.9987, respectively, P < 0.05). None of the MR analyses showed evidence of horizontal pleiotropy (P > 0.05) based on the MR-Egger and MR-PRESSO tests, and there was no statistical heterogeneity in the test results of the MR-Egger and IVW methods. The leave-one-out sensitivity analysis confirmed the robustness of the causal relationship between SS and PD. Furthermore, reverse MR analysis did not support any causal effects of PD on SS.ConclusionOur MR study supports a potential causal association between SS and a reduced risk of PD. Further extensive clinical investigations and comprehensive fundamental research are warranted to elucidate the underlying mechanisms linking SS and PD.

Introduction:Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5.Method:We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets.Results:Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75.Conclusion:The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.

BackgroundCognitive impairment is a prevalent condition that substantially elevates mortality rates among the elderly. The impact of hypertension on mortality in older adults with cognitive impairment is a subject of contention. This study aims to examine the influence of hypertension on both all-cause and CVD-specific mortality in elderly individuals experiencing cognitive impairment within a prospective cohort.MethodsThis study encompassed 2,925 participants (weighted 53,086,905) aged 60 years or older from National Health and Nutrition Examination Survey (NHANES) spanning 2011–2014. Incidence of all-cause and CVD-specific mortality was ascertained through linkage with National Death Index records until 31 December 2019. Survival was performed employing the Kaplan–Meier method. Hazard ratios (HRs) were calculated via Cox proportional hazards regression models.ResultsOver the follow-up period of up to 9.17 years [with a median (IQR) time to death of 6.58 years], equivalent to 18,731.56 (weighted 3.46 × 108) person-years, there were a total of 576 recorded deaths. Participants with CI exhibited a 1.96-fold higher risk of all-cause mortality (95% CI: 1.55–2.49; p < 0.01) and a 2.8-fold higher risk of CVD-specific mortality (95% CI: 1.83–4.29; p < 0.01) in comparison to participants without CI. Among participants with CI, concurrent hypertension comorbidity was linked to a 2.73-fold elevated risk of all-cause mortality (95% CI: 1.78–4.17; p < 0.01) and a 5.3-fold elevated risk of CVD-specific mortality (95% CI: 2.54–11.04; p < 0.01). Further stratified analyses revealed that the combined effects of hypertension and CI on all-cause and CVD-specific mortality were more pronounced in participants aged 60–69 years compared to those aged 70–80 years (p for interaction <0.01). The primary findings exhibited resilience across a series of sensitivity analyses.ConclusionsParticipants with CI exhibited a markedly elevated risk of all-cause and CVD-specific mortality when coexisting with hypertension. Appropriate management of hypertension in patients with CI may be helpful in reducing the excess risk of death.

BACKGROUND:Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE:To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aβ) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE:Retrospective. POPULATION:Thirty-eight Aβ-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aβ-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aβ-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aβ-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE:3.0T; DTI, T1-weighted, T2-weighted, T2 star-weighted angiography, and Aβ PET (18F-florbetaben or 11C-PIB). ASSESSMENT:FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS:Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS:Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION:FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL:4 TECHNICAL EFFICACY: Stage 2.

Objective:To investigate the impact of group-based rehabilitation exercise on motor and non-movement symptoms of Parkinson's disease(PD).Methods:A total of 88 patients from out-patient and in-patient services at our hospital were randomly assigned to an early exercise group(E-EG), a late exercise group(L-EG), and a control group(CG)using a randomized delayed-start design.Patients in the E-EG carried out a rigorous, formal group exercise program, one hour per session, twice per week, for 18 months(May 2018-November 2019). Patients in the L-EG took part in the exercise program in the final 6-12 months of the study.We assessed outcomes using the Unified Parkinson's Disease Rating Scale(UPDRS), Parkinson's disease questionnaire-39(PDQ-39 Q), trail-making test part A & B, nine-hole peg test(9-HPT), 30 second sit to stand test(30s SST), 10 m walk test(10 m W), mini-balance evaluation systems test(Mini-BEST), Fullerton Advanced Balance(FAB)Scale and time up and go(TUG)test.Results:Compared with pre-exercise levels, patients with PD in the E-EG had lower performance in UPDRS(17.5±8.3 vs.20.0±8.6, t=-2.2, P=0.02)and lower performance in PDQ-39(27.2±2.1 vs.29.0±9.8, t=-2.6, P=0.001)after exercise.Moreover, compared with pre-exercise levels, patients with PD in the E-EG showed decreased post-exercise performance in trail-making test part B(114.2±25.5 vs.129.8±28.4, t=-2.3, P=0.02)and in 9-HPT(33.7±7.3 vs.39.6±9.3, t=-2.6, P=0.001). Conclusions:The practice of group-based rehabilitation exercise can improve movement abilities and quality of life in PD patients, especially if implemented early.Targeted rehabilitation exercise should be taken as part of the treatment strategy for PD patients as early as possible to deliver the best benefits.

Abstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP‐induced histamine, N‐acetylputrescine, d‐aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD‐treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic‐pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet–gut microbiota–brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti‐inflammatory mechanisms of the gut–brain axis in PD models fed with KD.

目 的 通过7T磁共振磁敏感加权成像技术分析帕金森病(PD)患者黑质铁沉积情况.方法 收集2021年12月至2022年8月解放军总医院PD门诊确诊的原发性PD患者18例(PD组),选取同期年龄和性别匹配的健康体检者18例(对照组).用7T磁敏感加权成像序列扫描获取相位图并测量相位值,分析PD患者Hoehn-Yahr(H-Y)分期、统一帕金森病评定量表(UPDRS)总分和Ⅰ、Ⅱ、Ⅲ评分、39项帕金森病生活质量问卷(PDQ-39)评分等资料.结果 与对照组比较,PD组黑质面积较大[(223.03±30.60)mm2 vs(202.08±27.47)mm2,P＜0.05],而黑质相位值和致密部相位值明显降低[-0.03(-0.06,0.02)vs 0.04(-0.02,0.12),P＜0.01;0.16±0.10 vs 0.26±0.12,P＜0.01].PD组H-Y分期、UPDRS总分和Ⅰ、Ⅱ、Ⅲ评分及PDQ-39评分与黑质及致密部相位值不相关(P＞0.05).PD 组 2、3、5 层相位值较对照组明显降低[0.110(-0.009,0.226)vs 0.224(0.126,0.360),-0.022(-0.060,0.026)vs 0.042(-0.028,0.114),-0.112(-0.154,0.036)vs-0.030(-0.088,0.019),P＜0.05].结论 PD患者黑质铁沉积不均匀增加,体积增大,7T磁敏感加权成像对PD有一定诊断价值.

大脑后部皮质萎缩是一种少见的临床影像综合征，伴有视幻觉及注意力、醒觉水平波动的病例更是鲜有报道。本文报道了1例伴视幻觉及注意力、醒觉水平波动的大脑后部皮质萎缩的患者，并根据最新共识进行分层诊断。希望能够帮助临床医生更好地认识该病并进行分层诊断。.

目的:系统评价有氧运动对帕金森病患者认知功能的干预效果.方法:系统检索PubMed、Embase、Web of Science、The Cochrane Library、PsycINFO、中国知网数据库、万方数据库、维普数据库、中国生物医学文摘数据库,收集从建库至2022年5月22日公开发表的有氧运动干预帕金森病患者认知功能的随机对照试验和非随机对照试验.进行文献筛选、数据提取和质量评价后,采用Stata17.0软件进行Meta分析.结果:共纳入19项研究,Meta分析结果显示,与对照组比较,有氧运动可提高帕金森病患者的注意力(SMD= 0.31;95%CI 0.13～0.50;P＜0.001)、执行功能(SMD=0.59;95%CI 0.39～0.78;P＜0.001)、记忆力(SMD= 0.43;95%CI 0.09～0.77;P=0.02)评分.结论:有氧运动可以改善帕金森病患者的记忆力、执行功能和注意力,但其具体的运动剂量仍需要更多高质量的研究进一步完善.

BACKGROUND:Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms and non-motor symptoms, and affects millions of people worldwide. Growing evidence implies β-Hydroxybutyrate (BHB), one of the ketone bodies generated by ketogenesis, plays a neuroprotective role in neurodegenerative diseases. We aimed to verify the anti-inflammatory effect of BHB on PD and further explore potential molecular mechanisms.METHODS:We performed the experiments on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model in vivo and 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 cell model in vitro, with or without BHB pretreatment. Motor function was assessed by pole test, forced swimming test, traction test and open field test. Immunofluorescence was used to evaluate the loss of dopaminergic neurons and glial cell activation in MPTP-induced PD model mice. The expression of the STAT3/NLRP3/GSDMD signal pathway was measured by western blots. Proinflammatory cytokines was assessed by enzyme-linked immunosorbent assay (ELISA).RESULTS:BHB treatment reversed motor deficits, loss of dopaminergic neurons and glial cell activation in PD mice induced by MPTP. Moreover, BHB inhibited microglia pyroptosis by negatively regulating STAT3/NLRP3/GSDMD signal pathway, resulting in downregulation of proinflammatory cytokines (IL-1β and IL-18) in vivo and vitro.CONCLUSION:These data suggested BHB supplement inhibited pyroptosis by down-regulating STAT3-mediated NLRP3 inflammasome activation for PD models in vivo and in vitro. Our findings provided novel insights and available interventions for the prevention and treatment of PD, and highlighted pyroptosis as a potential therapeutic target for PD.

Parkinson's disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD.

BACKGROUND:Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer's disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-β (Aβ) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aβ deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice. OBJECTIVE:In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aβ pathologies, and expression of synaptic-associated proteins in APP/PS1 mice. METHODS:Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections. RESULTS:CEGI treatment in APP/PS1 mice significantly reduced Aβ deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aβ expression and PSD-95 palmitoylation in APP/PS1 mice. CONCLUSION:Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.

Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG ( n = 100) or placebo ( n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1), encoding the voltage-gated chloride channel ClC-1 in skeletal muscle. Our study reported the clinical and molecular characteristics of six patients with MC and systematically review the literature on Chinese people. We retrospectively analyzed demographics, clinical features, family history, creatine kinase (CK), electromyography (EMG), treatment, and genotype data of our patients and reviewed the clinical data and CLCN1 mutations in literature. The median ages at examination and onset were 26.5 years (range 11-50 years) and 6.5 years (range 1.5-11 years), respectively, in our patients, and 21 years (range 3.5-65 years, n = 45) and 9 years (range 0.5-26 years, n = 50), respectively, in literature. Similar to previous reports, myotonia involved limb, lids, masticatory, and trunk muscles to varying degrees. Warm-up phenomenon (5/6), percussion myotonia (3/5), and grip myotonia (6/6) were common. Menstruation triggered myotonia in females, not observed in Chinese patients before. The proportion of abnormal CK levels (4/5) was higher than data from literature. Electromyography performed in six patients revealed myotonic changes (100%). Five novel CLCN1 mutations, including a splicing mutation (c.853 + 4A>G), a deletion mutation (c.2010_2014del), and three missense mutations (c.2527C>T, c.1727C>T, c.2017 G > C), were identified. The c.892 G > A (p.A298T) mutation was the most frequent mutation in the Chinese population. Our study expanded the clinical and genetic spectrum of patients with MC in the China. The MC phenotype in Chinese people is not different from that found in the West, while the genotype is different.

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As a diet mimicking fasting, it triggers the production of ketone bodies (KBs) and brings the body into a state of ketosis. Recent and accumulating studies on humans and animal models have shown that KD is beneficial to neurodegenerative diseases through modulating central and peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, and the gut microbiome. Complicated interplay of metabolism, gut microbiome, and other mechanisms can regulate neuroinflammation in neurodegenerative diseases by activating multiple molecular and cellular pathways. In this review, we detail the physiological basis of the KD, its functions in regulating neuroinflammation, and its protective role in normal brain aging and neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We aimed to elucidate the underlying neuroinflammatory mechanisms of KD therapies in neurodegenerative diseases and provide novel insights into their application for neurodegenerative disease prevention and treatment.

随着我国人口老龄化的进展,老年神经病学越来越引起人们的重视.为了提升老年神经病学的教学效果,文章采用线上病例讨论的教学方法,通过线上病例汇报、主管医师补充、专家点评拓展的方式进行,并对线上病例讨论需要改进的地方进行了说明,为老年神经病学教学提供新的思路.