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Background: Neurodegenerative disease pathology is associated with neuroinflammation, but evidence on idiopathic normal pressure hydrocephalus (iNPH) remains limited and cerebrospinal fluid (CSF) biomarker profiles need to be elucidated. Objective: To investigate whether iNPH pathological mechanisms are associated with greater CSF markers of core Alzheimer’s disease pathology (amyloid-β42 (Aβ 42), phosphorylated tau (P-tau)), neurodegeneration (total tau (T-tau)), and neuroinflammation (soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase-3-like protein 1 (YKL-40)). Methods: The study analyzed lumbar CSF samples from 63 patients with iNPH and 20 age-matched orthopedic surgery patients who had no preoperative gait or cognitive impairment (control group). Aβ 42, T-tau, P-tau, sTREM2, and YKL-40 in different subgroups were investigated. Results: CSF sTREM2 levels were significantly higher in the iNPH group than in the control group, but no significant between-group difference was noted in YKL-40. Moreover, YKL-40 levels were significantly higher in the tap test non-responders than in the tap test responders (p = 0.021). At the 1-year follow-up after shunt surgery, the CSF P-tau levels were significantly lower (p = 0.020) in those with gait improvement and the CSF sTREM2 levels were significantly lower (p = 0.041) in those with cognitive improvement. In subgroup analysis, CSF sTREM2 levels were strongly correlated with CSF YKL-40 in the iNPH group (r = 0.443, p

The aim of this study was to analyze cortical thickness and gray matter volume (GMV) changes in white matter hyperintensities (WMH) which were associated brain regions and their association with mild behavioral impairment (MBI) by means of voxel- and surface-based morphology (VBM and SBM).A total of 60 patients underwent 3T MRI scan and MBI checklist (MBI-C) assessment and were divided into two groups: lower WMH (LWMH) and higher WMH (HWMH). After adjusting for confounding factors i.e. age, gender, education, and total intracranial volume, we found a GMV decrease in the left anterior insula (AIns), right middle frontal gyrus, right central operculum, right fusiform gyrus, left cerebellum exterior, and thalamus proper in the HWMH group based VBM, while in the HWMH group based SBM we found cortical thickness decrease in the left lingual, right posterior cingulate cortex (rPCC), right precentral, left superior frontal, right medial orbitofrontal gyrus, and left pars opercularis.The HWMH group had higher MBI-C scores. The GMV in the left AIns and thalamus proper and the thickness of rPCC negatively correlated with the MBI-C scores. The mediation analysis suggested that WMH may partially mediate MBI-C scores by reducing the GMV and cortical thickness of the mentioned brain regions.In WMH patients, the occurrence of MBI is associated with atrophy of gray matter and cortex. The occurrence of MBI may be partially mediated by WMH through gray matter and cortical atrophy. It provides a new insight into the relationship between WMH and dementia.

Stress is not scarce in peoples' daily life that may result in mental diseases and cognitive impairments. Chronic restraint stress (CRS) is a well-validated animal model used to investigate the mechanism of stress-associated depression and cognitive impairments. Dl-3-n-butylphthalide (NBP) possesses anti-oxidant, anti-inflammatory and anti-apoptotic, promoting neurogenesis and neuroplasticity that exerts neuroprotective effects. However, the effects of NBP on CRS-induced depression and cognitive impairments remain unclear.C57BL/6 male mice were randomly divided into the control group, stress group and stress+NBP group. Mice were exposed to CRS for three consecutive weeks and mice in the NBP treatment group were administered with NBP before the CRS procedure. After that, depression and cognition behaviors were evaluated followed by phosphorylation of Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylation of cAMP-response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) proteins expression, immunohistochemistry of hippocampal postsynaptic density 95 (PSD95) and synaptophysin, and hippocampal morphology.Our results showed that mice exhibited depression-like behaviors and cognitive deficits after 3 weeks exposure to CRS. Additionally, CRS downregulated CaMKII/CREB/BDNF signaling pathway, reduced PSD95 and synaptophysin expression and induced hippocampal CA1 and dentate gyrus ment significantly reversed the hippocampal pathological and molecular changes induced by CRS.In conclusion, these results reveal that NBP exerts a neuroprotective effect on depression and cognitive deficit through activating CaMKII/CREB/BDNF pathway, enhancing PSD95 and synaptophysin expression and protecting hippocampal morphology.

Alzheimer's disease (AD) is the most common cognitive disorder in the elderly. Its main clinical manifestations are cognitive decline (C), behavioral and psychological symptoms (B), and a decline in the activities of daily living (A), also known as ABC symptoms. Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis, comprehensive treatment, and prognosis of AD. To guide Chinese clinical practice for optimization of the comprehensive management of AD, in 2018, The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD. Based on a review of the evidence, the consensus summarizes the pathogenesis, pathological changes, clinical manifestations, evaluation, diagnosis, drug and non-drug treatment, and patient care for AD. Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients. The new consensus provides a feasible AD management process for clinicians.

A cross-sectional study was conducted to evaluate patterns of gray matter changes in cognitively normal elderly adults with mild behavioral impairment (MBI). Sixteen MBI patients and 18 healthy controls were selected. All the participants underwent a neuropsychological assessment battery, including the Mini-mental State Examination (MMSE), Geriatric Depression Scale (GDS), Self-rating Anxiety Scale (SAS), and Chinese version of the mild behavioral impairment-checklist scale (MBI-C), and magnetic resonance imaging (MRI) scans. Imaging data was analyzed based on voxel-based morphometry (VBM). There was no significant difference in age, gender, MMSE score, total intracranial volume, white matter hyperdensity, gray matter volume, white matter volume between the two groups (p > 0.05). MBI group had shorter education years and higher MBI-C score, GDS and SAS scores than the normal control group (p < 0.05). For neuroimaging analysis, compared to the normal control group, the MBI group showed decreased volume in the left brainstem, right temporal transverse gyrus, left superior temporal gyrus, left inferior temporal gyrus, left middle temporal gyrus, right occipital pole, right thalamus, left precentral gyrus and left middle frontal gyrus(uncorrected p < 0.001). The grey matter regions correlated with the MBI-C score included the left postcentral gyrus, right exterior cerebellum, and left superior frontal gyrus. This suggests a link between MBI and decreased grey matter volume in cognitively normal elderly adults. Atrophy in the left frontal cortex and right thalamus in MBI patients is in line with frontal-subcortical circuit deficits, which have been linked to neuropsychiatric symptoms (NPS) in dementia. These initial results imply that MBI might be an early harbinger for subsequent cognitive decline and dementia.

Diabetes is a risk factor for Parkinson's disease (PD) and shares similar dysregulated insulin pathways. Glucagon-like peptide-1 (GLP-1) analogs originally designed to treat diabetes have shown potent neuroprotective activity in preclinical studies of PD. They are neuroprotective by inhibiting inflammation, improving neuronal survival, maintenance of synapses, and dopaminergic transmission in the brain. Building on this, three clinical studies have reported impressive effects in patients with PD, testing -4 (Exenatide, Bydureon) or liraglutide (Victoza, Saxenda). Glucose-dependent insulinotropic peptide (GIP) is another peptide hormone that has shown good effects in animal models of PD. Novel dual GLP-1/GIP agonists have been developed that can penetrate the blood-brain barrier (BBB) and show superior effects in animal models compared to GLP-1 drugs.The review summarizes preclinical and clinical studies testing GLP-1R agonists and dual GLP-1/GIPR agonists in PD and discusses possible mechanisms of action.Current strategies to treat PD by lowering the levels of alpha-synuclein have not shown effects in clinical trials. It is time to move on from the 'misfolding protein' hypothesis. Growth factors such as GLP-1 that can cross the BBB have already shown impressive effects in patients and are the future of drug discovery in PD.

Post-stroke fatigue (PSF), a highly distressing symptom, could exert an influence on the quality of life of stroke survivors. A previous meta-analysis reported that PSF was associated with mood disturbances such as depressive symptoms and anxiety. However, the association between stroke characteristics (stroke type and location) and PSF remains unclear.We performed a meta-analysis to study the association between stroke characteristics and PSF.We conducted a search of electronic databases (PubMed, Web of Science, Cochrane Library) from the inception of all databases up to July 9, 2019. The quality of eligible articles was evaluated. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to represent the combined effect value of each study.Eight eligible studies including a total of 1816 stoke patients were identified. Three studies discussed the association between stroke type and PSF, and five studies investigated the relationship between stroke location and PSF. The results demonstrated PSF had a strong correlation with stroke type (OR = 2.42, 95% CI = [1.27, 4.61], P = 0.007) but was not relevant to stroke location, indicating that PSF was a complex, heterogeneous syndrome and that stroke characteristics may play only a very small role in the risk of developing PSF.Our meta-analysis indicated that PSF was closely relevant to stroke type and had no significant relationship with stroke location. However, the findings should be interpreted cautiously. Thus, we suggest an updated meta-analysis on this subject when more comprehensive studies that explore the above issue are available.

Background and Purpose: White matter hyperintensities (WMH) caused by chronic cerebral hypoperfusion are common in Moyamoya disease (MMD) patients, but WMH burden with comprehensive cognition in adult asymptomatic MMD remains unknown. This study tried to investigate the association between the WMH burden and cognitive function in adult asymptomatic MMD. Methods: Sixty-four adult asymptomatic MMD patients without surgical revascularization were enrolled in this study and underwent a 3T MRI scan and complete cognitive tests from 2021 to 2022. WMH volume was extracted with brain anatomical analysis using the diffeomorphic deformation (BAAD) toolbox, which works on SPM 12 software. Multivariable linear regression analysis was performed to assess the association between WMH burden and cognitive function in asymptomatic MMD. Results: Firstly, our data showed that lower education levels and higher WMH burden were strongly related to global cognitive impairment after adjusting for other variables. Secondly, WMH severity was significantly associated with several domains of neurocognitive function, including memory, semantic memory, and executive function. Finally, when stratified by sex, the female participants with WMH severity had lower cognitive performance in all areas than male participants. Conclusions: These results suggest that WMH burden was highly correlated with global cognition, memory, semantic memory, and executive function in asymptomatic MMD. Especially in female participants, the relationship became more evident.

Mild behavioral impairment (MBI), characterized by the late-life onset of sustained and meaningful neuropsychiatric symptoms, is increasingly recognized as a prodromal stage of dementia. However, the underlying neural mechanisms of MBI remain unclear. Here, we examined alterations in the topological organization of the structural covariance networks of patients with MBI (N = 32) compared with normal controls (N = 38). We found that the gray matter structural covariance networks of both the patients with MBI and controls exhibited a small-world topology evidenced by sigma value larger than one. The patients with MBI had significantly decreased clustering coefficients at several network densities and local efficiency at densities ranging from 0.05 to 0.26, indicating decreased local segregation. No significant differences in the characteristic path length, gamma value, sigma value, or global efficiency were detected. Locally, the patients with MBI showed significantly decreased nodal betweenness centrality in the left middle frontal gyrus, right inferior frontal gyrus (opercular part), and left Heschl gyrus and increased betweenness centrality in the left gyrus rectus, right insula, bilateral precuneus, and left thalamus. Moreover, the difference in the bilateral precuneus survived after correcting for multiple comparisons. In addition, a different number and distribution of hubs was identified in patients with MBI, showing more paralimbic hubs than observed in the normal controls. In conclusion, we revealed abnormal topological patterns of the structural covariance networks in patients with MBI and offer new insights into the network dysfunctional mechanisms of MBI.

Background: Early morning off (EMO) refers to off-states in the morning in people diagnosed with Parkinson's disease (PwPD). This study determined the clinical manifestations of EMO and the association with nocturnal sleep problems and quality of life (QOL) in Chinese PwPD.Methods: In this multicenter, observational, cross-sectional study, data concerning the clinical manifestations of EMO were collected from PwPD in Shanghai by questionnaire. The stepwise logistic regression was performed to analyze the potential risk factors, as well as whether EMO was an independent risk factor for functional dependency in daily life. The mediation analyses were conducted to evaluate whether nocturnal sleep problems might mediate the association between EMO and the QOL.Results: Among the 454 subjects evaluated, EMO occurred in 39.43% of PwPD across all disease stages. The prevalence of EMO increased as the Hoehn and Yahr stage increased and was observed in 35.60% of patients in stages 1–2.5 and 48.85% of patients in stages 3–5. EMO was associated with non-motor symptoms (NMSs). The predominant NMSs associated with EMO were nocturnal sleep problems (98.90%), mood/cognition impairment (93.90%), decreased attention/memory (91.60%), gastrointestinal symptoms (91.60%), and urinary urgency (90.50%). The QOL of PwPD with EMO was significantly reduced (P < 0.001). Moreover, nocturnal sleep problems might partially mediate this relationship (indirect effect: β = 13.458, 95% boot CI: 6.436, 22.042).Conclusion: PwPD have EMO throughout all stages of the disease. Patients with EMO have severe motor symptoms and NMSs. EMO decreases the QOL in PwPD and this relationship is partially mediated by nocturnal sleep problems. In light of these findings, it is suggested that recognition and appropriate treatment of EMO and nocturnal sleep problems could improve the management of PwPD.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are common in the general elderly population, conferring heavy individual, social, and economic stresses on families and society. Accumulating evidence indicates T2D to be a risk factor for AD. However, the underlying mechanisms for this association are largely unknown. This study aimed to identify the shared molecular signatures between AD and T2D through integrated analysis of temporal cortex gene expression data. Gene Ontology (GO) and pathway enrichment analysis, protein over-representation analysis, protein-protein interaction, DEG-transcription factor interactions, DEG-microRNA interactions, protein-drug interactions, gene-disease association analysis, and protein subcellular localization analysis of the common DEGs were performed. We identified 16 common DEGs between the two datasets, which were mainly enriched in the biological processes of apoptosis, autophagy, inflammation, and hemostasis. We also identified five hub proteins encoded by the DEGs, five central regulatory transcription factors, and six microRNAs. Protein-drug interaction analysis showed C1QB to be associated with different drugs. Gene-disease association analysis revealed that hub genes, SFN and ITGB2, were actively engaged in other diseases. Collectively, these findings provide new insights into shared molecular mechanisms between AD and T2D and provide novel candidate targets for therapeutic intervention.

Indoleamine 2,3-dioxygenase 1 (IDO-1) is an immunosuppressive enzyme expressed in the placenta, neoplastic cells, and macrophages to reject T cells by converting tryptophan into kynurenine. However, the role of IDO-1 in brain immunity, especially in the meninges, is unclear. We aim to elucidate the distribution pattern of IDO-1+ macrophages/microglia in the human brain tissues, human glioblastoma, APP/PS1 mouse brains, and quinolinic acid model brains and explore the physiological and immunological roles of IDO-1+ macrophages/microglia. Here, we find that both human and mouse macrophages/microglia of the perivascular and subarachnoid space and in glioblastoma (GBM) expressed IDO-1 but not macrophages/microglia of parenchyma. Using IDO-1 inhibitors including 1-MT and INCB24360, we observed that inhibiting IDO-1 reduced the cellular size and filopodia growth, fluid uptake, and the macropinocytic and phagocytic abilities of human blood monocytes and RAW264.7/BV-2 cells. Inhibiting IDO-1 with 1-MT or INCB24360 increased IL-1β secretion and suppressed NLRP3 expression in RAW264.7/BV-2 cells. Our data collectively show that IDO-1 expression in perivascular and meninges macrophages/microglia increases cellular phagocytic capacity and might suppress overactivation of inflammatory reaction.

We model a dynamic data economy with fully endogenous growth where agents generate data from consumption and share them with innovation and production firms. Different from other productive factors such as labor or capital, data are nonrival not only among firms but also in their uses across sectors, which affect both the level and growth of economic outputs. Despite the vertical nonrivalry, the innovation sector dominates the production sector in data usage and contribution to growth because (i) innovations are cumulative and benefit from data that are durable and dynamically nonrival; and (ii) innovations "desensitize" raw data into knowledge when entering production, which allays consumers' privacy concerns. Data uses in both sectors interact in generating allocative distortions and an apparent substitutability due to labor's rival usage across sectors and complementarity with data. Consequently, growth rates diverge under a social planner and a decentralized equilibrium, which is novel in the literature and has policy implications. Specifically, consumers' failure to fully internalize knowledge spillover while bearing privacy costs, combined with firms' market power, leads to an underpricing of data and inefficient data supply, causing underemployment in the innovation sector and suboptimal long-run growth. Improving data usage efficiency is ineffective in mitigating the underutilization of data, but interventions in the data market and direct subsidies hold promises.

Background: Macrophages switch between different functional phenotypes under the different physiological or path-physiological stimuli in tissue. Macrophage functional phenotype heavily affects disease progression, including inflammation, injury, neurodegenerative disease, and cancers. IDO-1, a druggable target, is an immunosuppressive enzyme expressed in tissue macrophages and induced by Interferon-γ (IFN-γ). How IDO-1 inhibitors affect the functional switches of macrophage are unknown. Methods: IFN-γ were used to increase IDO-1 expression and 1-Methyl-D-tryptophan (1-MT) and INCB24360 (Epacadostat) were used to inhibit IDO-1 activity in RAW264.7 and BV-2. Western blotting, immunostaining and ELISA were used to evaluate protein expressions or secretion. RT-PCR were used to assess to transcription. TMR-Dextran and Latex beads were used to test endocytic, macropinocytic and phagocytic ability of macrophage and Fiji image and IMARIS were used to analyze images.Results: Our results showed that INCB24360 preferentially suppresses the cellular size and filopodia growth and reduces fluid uptake, macropinocytosis, and phagocytic ability of IFN-γ induced or non-induced RAW264.7 and BV-2 in vitro. 1-MT and INCB24360 suppress IFN-γ induced or endogenous NLRP3 expression levels but not caspase-1 in RAW264.7 and BV-2. NLRP3 reduction induced by 1-MT and INCB24360 parallel with the decrease of NLRP3 gene transcription and an increase of IL-1β secretion. Conclusions: Our data collectively showed that inhibiting IDO-1 with its inhibitors, especially INCB24360, preferentially suppresses cellular size and filopodia growth, NLRP3 expression, the endocytic, macropinocytic, and phagocytic capacity whereas increases IL-1β secretion in macrophage. Our findings do not rule out the roles of IDO-1 in the formation of M1-like macrophages, but they cast doubt on the robust anti-inflammatory effects of IDO inhibitors in the macrophage-mediated immune response.

By tuning the metal ratio, a Z-scheme g-C3N4/MgAlFeO nanorod composite was prepared in situ. The nitrogen photofixation performance under visible light was tested to evaluate the performance of the prepared catalysts. Strong electronic coupling, as evidenced by the XPS, PL and EIS results, exists between the two components in the g-C3N4/Mg1.1Al0.3Fe0.2O1.7 heterojunction photocatalysts, leading to a more effective separation of photogenerated electron–hole pairs and faster interfacial charge transfer, causing the higher activity and stability for N2 photofixation. Neat MgAlFeO shows almost no N2 photofixation activity. However, with the MgAlFeO mass percentage of 23.6%, the as-prepared heterojunction photocatalyst exhibits the highest NH4+ generation rate under visible light, which is 3.5-fold greater than that of individual g-C3N4. A possible Z-scheme mechanism is proposed.

BACKGROUND Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. OBJECTIVE To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). METHODS The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naive AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. RESULTS 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p

Huntington’s disease (HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein (mHTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here, we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected mHTT in Neuro-2a cells and endogenous mHTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected mHTT in Neuro-2a cells, endogenous mHTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose- and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal mHTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-019-00421-5) contains supplementary material, which is available to authorized users.

Background Major depressive disorders (MDD) is one of the most common mental illness in the world. Recently, brain m6A /m (fat mass- and obesity-associated gene Fto) was found that exerted an important role in regulating gene expression involved in stress related depression. However, the potential mechanism of Fto on depression still remains elusive. This study investigated the role of Fto and its downstream signaling pathway in hippocampus on chronic restraint stress induced depressive-like behaviors. Methods C57BL/6 mice weighing 20−22 g were randomly divided into 4 groups (Control, Control + Fto-ov, Stress, Stress + Fto-ov). Mice were exposed to chronic restraint stress for 3 consecutive weeks to induce depression model. Mice in the Fto-ov groups were stereotaxic injected with Recombinant Adeno-associated Virus lentivirus (Fto) in hippocampus followed by stress procedure. Depressive-like behaviors were detected after stress procedure. Western blot was used to test hippocampal Fto, p-CaMKII and p-CREB expression. Post synaptic density protein 95 (PSD95) and synaptophysin levels were detected by PCR. Golgi-Cox staining was used to appraise dendritic spine density and branches. Synaptic morphology in hippocampus was determined by electron microscopy. Results We demonstrated that chronic restraint stress induced depressive-like behaviors, decreased protein expression of Fto, p-CaMKII and p-CREB, reduced levels of synaptic plasticity markers (synaptophysin and PSD95) in hippocampus. Moreover, chronic restraint stress led to synaptic morphology alterations (reduced dendritic spine density and number of branches; thinned postsynaptic density). However, these molecules changes and morphology alterations were reversed by stereotaxic injected recombinant adeno-associated Fto-overexpression virus in hippocampus. Conclusions This study found that the modulation of Fto on CaMKII/CREB signaling pathway plays a key role in hippocampal synaptic plasticity, and then ameliorated chronic restraint stress induced depressive-like behaviors.

Damage to memory circuits may lead to dementia symptoms in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Recently, deep brain stimulation (DBS) has been shown to be a novel means of memory neuromodulation when critical nodes in the memory circuit are targeted, such as the nucleus basalis of Meynert (NBM) and fornix. Potential memory improvements have been observed after DBS in patients with AD and PDD. DBS for the treatment of AD and PDD may be feasible and safe, but it is still preliminary. In this review, we explore the potential role of DBS for the treatment of dementia symptoms in AD and PDD. Firstly, we discuss memory circuits linked to AD and PDD. Secondly, we summarize clinical trials and case reports on NBM or fornix stimulation in AD or PDD patients and discuss the outcomes and limitations of these studies. Finally, we discuss the challenges and future of DBS for the treatment of AD and PDD. We include the latest research results from Gratwicke et al. (2017) and compare them with the results of previous relevant studies, and this would be a worthy update of the literature on DBS for dementia. In addition, we hypothesize that the differences between AD and PDD may ultimately lead to different results following DBS treatment.

Nicotinamide adenine dinucleotide (NAD+) repletion has been shown to provide marked neuroprotection from genotoxic agent-induced neuronal and astrocyte cell death. One of the key precursors of NAD+ is nicotinamide mononucleotide (NMN). Therefore, it was hypothesized that NMN may attenuate apoptosis and improve energy metabolism in Parkinson’s disease (PD)-like behavioral and neuropathological changes, and produce significant beneficial effects. In this study, a cellular model of PD, using rotenone-treated PC12 cells, was established to test the hypothesis that NMN may decrease PD-like pathological changes. Experiments were carried out to investigate cell survival, including an intracellular lactate dehydrogenase (LDH) assay. Apoptotic and necrotic cell death, NAD+ levels and ATP levels were also evaluated. It was observed that NMN was able to significantly attenuate the rotenone-induced reduction in the survival rate of PC12 cells, as assessed by MTT and LDH assays. NMN treatment also significantly reduced the rotenone-induced apoptosis of the cells, as assessed by flow cytometry-based Annexin V/7-aminoactinomycin D staining. Furthermore, NMN restored intracellular levels of NAD+ and ATP in the rotenone-treated cells, thus demonstrating the capacity of NMN to ameliorate mitochondrial inhibitor-induced impairments of energy metabolism. The present study indicates that NMN produces significant beneficial effects by attenuating apoptosis and improving energy metabolism in a cellular model of PD. These results suggest that NMN may become a promising therapeutic drug for PD.

Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD).Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted.Literature review showed that RCD definitions varied. Mini-Mental State Examination scores20 at treatment onset, vascular risk factors, age70 years at symptom onset, higher education levels, and early appearance of hallucinations, psychosis, or extrapyramidal symptoms are recognized RCD risk factors. Chart review showed that RCD (Mini-Mental State Examination score decline ≥3 points/year) is more common in moderate (43.2%) than in mild patients (20.1%; P .001). Rapid and slow decliners had similar age, gender, and education levels at baseline.RCD is sufficiently common to interfere with randomized clinical trials. We propose a 6-month prerandomization determination of the decline rate or use of an RCD risk score to ensure balanced allocation among treatment groups.

The early detection of subjects with probable cognitive deficits is crucial for effective appliance of treatment strategies. This paper explored a methodology used to discriminate between evoked related potential signals of stroke patients and their matched control subjects in a visual working memory paradigm. The proposed algorithm, which combined independent component analysis and orthogonal empirical mode decomposition, was applied to extract independent sources. Four types of target stimulus features including P300 peak latency, P300 peak amplitude, root mean square, and theta frequency band power were chosen. Evolutionary multiple kernel support vector machine (EMK-SVM) based on genetic programming was investigated to classify stroke patients and healthy controls. Based on 5-fold cross-validation runs, EMK-SVM provided better classification performance compared with other state-of-the-art algorithms. Comparing stroke patients with healthy controls using the proposed algorithm, we achieved the maximum classification accuracies of 91.76% and 82.23% for 0-back and 1-back tasks, respectively. Overall, the experimental results showed that the proposed method was effective. The approach in this study may eventually lead to a reliable tool for identifying suitable brain impairment candidates and assessing cognitive function.

Chorea is a rare complication of polycythemia. We report the case of a 70 year-old woman whose polycythemia vera (PV), with Janus Kinase-2 (JAK2) mutation, presented as chorea. Chorea resolved quickly after hydroxyurea therapy.