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Aggregation-induced emission (AIE) molecules have great potential to enhance the performance of micronano lasers due to their excellent aggregated luminescence properties, so it is valuable to expand their applications in micronano lasers. In this work, a typical AIE active fluorescent dye motif 9,10-bis(2,2-diphenylvinyl) anthracene (BDPVA) was selected as the gain medium. First, drop-casting was used to fabricate BDPVA single-crystal nanowires, which can be used as Fabry-Perot (FP)-type resonators with a lasing threshold of 49.4 µJ/cm2. Furthermore, we innovatively doped BDPVA molecules as gain mediums into external polymer Whispering-Gallery-Mode (WGM)-type resonators via the emulsion self-assembly method. Fabricated BDPVA-doped polystyrene (PS) microspheres exhibit a much lower lasing threshold of 9.04 µJ/cm2. These results prove that the BDPVA molecules, in addition to realizing the reported AIE single-crystal lasers, can also be used as a guest-doped gain medium in the resonant cavity for obtaining better fluorescence gain. In addition, multimode tunability of two types of lasers has been successfully achieved by tuning the structure of the resonant cavity. This work further expands the application potential of AIE materials and will provide a useful reference for the rational design and fabrication of photonic micronano laser components using AIE materials.
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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by progressive degeneration of motor neurons. Genetic factors have a substantial impact on ALS. Therefore, this study aimed to explore the correlation between genotype (SOD1, TARDBP, FUS, C9orf72) and phenotype in ALS. METHODS: Genetic analysis was performed on 2038 patients with ALS, among which 1696 patients with sporadic ALS (SALS) as controls for genotype-phenotype analysis, and 1602 SALS as controls for survival analysis. Logistic regression and Cox proportional hazards models were used for statistical analysis. RESULTS: A total of 172 patients with ALS with the gene mutations were included in the statistical analysis (SOD1, n=65; FUS, n=43; TARDBP, n=27; C9orf72, n=37). SOD1 mutations were more frequent in flail leg phenotype (OR 7.317, p=0.001) and less in bulbar phenotype (OR 0.222, p=0.038). C9orf72 expansions exhibited higher frequency in bulbar phenotype (OR 2.770, p=0.008). SOD1 and FUS mutations were significantly associated with earlier age of onset (HR 2.039, p<0.001; HR 1.762, p=0.001). The patients with SOD1 mutations, C9orf72 expansions and those carrying pathogenic FUS mutations had significantly increased death risk (HR 2.217, p<0.001; HR 1.694, p=0.008; HR 1.652, p=0.036). The increased risk of death in ALS with C9orf72 expansions was significant in females (HR 2.419, p=0.014) but not in males (HR 1.442, p=0.128). CONCLUSION: Our study revealed distinct motor phenotypic tendencies in patients with ALS with different genotypes, indicating variations in the vulnerability of motor neurons during the disease's progression. Furthermore, we made novel discoveries regarding survival of different gene mutations, warranting further investigation.
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BACKGROUND: Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. METHODS: To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. RESULTS: The cohort was followed up for an average of 5.25 (SEâ =â 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (pâ =â 8.63E-09, betaâ =â 1.74, SEâ =â 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1 000 iterations. CONCLUSIONS: These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.
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Disfunção Cognitiva , Dipeptidil Peptidases e Tripeptidil Peptidases , Estudo de Associação Genômica Ampla , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/complicações , Masculino , Feminino , Disfunção Cognitiva/genética , Idoso , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Predisposição Genética para Doença , Pessoa de Meia-Idade , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Estudos Longitudinais , Modelos de Riscos Proporcionais , China/epidemiologia , Proteínas do Tecido Nervoso , Canais de PotássioRESUMO
The excited-state energy transfer widely exists in mixed-material systems and devices. The modulation of an electric field on the energy transfer in photoluminescence has been demonstrated. However, to date, no studies on the electric-field modulation of the excited-state energy transfer in organic optoelectronic devices have been reported. Herein, we investigate the effect of an electric field on the energy transfer in the poly(N-vinylcarbazole) (PVK) thin films doped with iridium(iii)[bis(4,6-difluorophenyl)pyridinato-N,C2']-tetrakis(1-pyrazolyl)borate (Fir6) and 5,6,11,12-tetraphenylnaphthacene (rubrene) (PVK:Fir6:rubrene) and the corresponding light-emitting diodes. Combined with the Onsager model describing electric-field enhanced exciton dissociation, we find that the electric field increases the rate of Dexter energy transfer from Fir6 to rubrene in the films and the diodes. The voltage-dependent color shift in the PVK:Fir6:rubrene light-emitting diodes can be explained by the electric-field enhanced Dexter energy transfer from Fir6 to rubrene. Our findings are important for the control of energy transfer process in organic optoelectronic devices by an electric field for desirable applications.
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BACKGROUND: Excessive daytime sleepiness (EDS) is one of the most frequent nonmotor symptoms in Parkinson's disease (PD); however, the pathogenesis of EDS is unclear, and there is a lack of information on plasma biomarkers for EDS in PD. We aimed to investigate the plasma biomarkers of EDS in a large PD cohort. METHODS: A total of 159 PD patients were included in the prospective cohort study and followed up annually for 3 years. Plasma biomarkers including glial fibrillary acidic protein, amyloid-beta, p-tau181, and neurofilament light chain (NfL), were measured using an ultrasensitive single-molecule array (Simoa) technology at each visit. EDS was evaluated using the Epworth Sleepiness Scale (ESS). RESULTS: The frequency of EDS in PD increased from 15.1% at baseline to 25.0% after 3 years. The mean ESS scores increased from 5.1 (standard deviation [SD]: 4.8) at baseline to 6.1 (SD: 5.5) at the third year of follow-up. At baseline, compared with patients with PD without EDS, those with EDS were more likely to be male, had poorer cognitive performance, and more severe motor and nonmotor symptoms. The adjusted generalized estimating equations models showed that higher plasma NfL levels (OR: 1.047 [1.002-1.094], pâ =â .042) were associated with EDS during follow-ups. The adjusted linear mixed-effects model showed that higher plasma NfL levels (ß 0.097 [0.012-0.183], pâ =â .026) were associated with ESS scores during follow-ups. CONCLUSIONS: Higher plasma NfL levels were associated with EDS in PD, indicating an association between neuro-axonal degeneration and EDS in PD.
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Biomarcadores , Distúrbios do Sono por Sonolência Excessiva , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Masculino , Feminino , Biomarcadores/sangue , Idoso , Estudos Prospectivos , Distúrbios do Sono por Sonolência Excessiva/sangue , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Proteínas de Neurofilamentos/sangue , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Estudos LongitudinaisRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. METHODS: A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. RESULTS: We found that ALS patients had significantly higher percentage of CD4+ T cells (39.3 vs. 37.1%, p < 0.001) and CD4+/CD8+ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4+ T cells, and CD4+/CD8+ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361-0.973). CONCLUSION: We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4+ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS.
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Esclerose Lateral Amiotrófica , Progressão da Doença , Humanos , Esclerose Lateral Amiotrófica/imunologia , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Linfócitos T CD4-Positivos/imunologia , Imunoglobulina G/sangueRESUMO
The strong Lewis acid tin halide leads to an excessively fast crystallization rate, resulting in more defects in the film and degraded device performance. In this work, a cesium acetate (CsAc) pre-buried poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole transport layer acts as nucleation points during the crystallization of tin-based perovskite, which can induce preferential orientation growth of crystals and increase the grain size to improve the quality of crystallization. The addition of CsAc not only can increase the conductivity of PEDOT:PSS but also can improve the wettability of the perovskite precursor solution to enhance the interface contact between the hole transport layer and perovskite layer. Because of the incorporation of CsAc in PEDOT:PSS, the average short-circuit current density increases from 23.80 to 27.60 mA cm-2. Furthermore, a power conversion efficiency of 10.99% is achieved for a tin-based perovskite solar cell with CsAc-doped PEDOT:PSS as the hole transport layer.
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OBJECTIVE: We aimed to examine the longitudinal change of plasma neurofilament light chain (NFL) level and explore its diagnostic and prognostic implications in Parkinson's disease (PD). METHODS: A total of 184 patients with early PD who completed 5-year annually repeated clinical assessments were included. Plasma NFL at baseline, 1 year, and 2 year were examined, which were quantified using the ultrasensitive Simoa technology. At baseline, blood from 86 sex- and age-matched healthy controls (HC) were obtained for comparison. RESULTS: Plasma NFL in PD patients at baseline was significantly higher than those in HC (P = 0.046), and significantly increased after 2 years (P = 0.046). Receiver operating characteristic curve indicated that a plasma NFL cut-off value of 10.79 pg/mL resulted in 39.7% sensitivity and 84.0% specificity, with an area under the curve of 0.635, to distinguish PD from HC (P < 0.001). Linear mixed-effect models indicated that baseline plasma NFL (> 9.24 pg/mL) correlated with a greater increase in the Unified Parkinson's Disease Rating Scale III (estimate = 0.651, P = 0.001) and Hoehn & Yahr stage (estimate = 0.072, P < 0.001), and also correlated with a greater decrease in the Montreal Cognitive Assessment (estimate = - 0.387, P < 0.001) during follow-up visits. CONCLUSIONS: Plasma NFL exhibits a tendency to increase with disease progression, and elevated baseline plasma NFL can serve as a predictor for accelerated motor deterioration and cognitive decline in PD. However, plasma NFL does not have high accuracy to distinguish individuals with early-stage PD from HC.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Estudos Prospectivos , Proteínas de Neurofilamentos , Testes de Estado Mental e Demência , Progressão da Doença , BiomarcadoresRESUMO
Age at onset may be an important feature associated with distinct subtypes of amyotrophic lateral sclerosis (ALS). Little is known about the neuropathological mechanism of early-onset ALS (EO-ALS) and late-onset ALS (LO-ALS). Ninety ALS patients were divided into EO-ALS and LO-ALS group, and 128 healthy controls were matched into young controls(YCs) and old controls (OCs). A voxel-based morphometry approach was employed to investigate differences in gray matter volume (GMV). Significant age at onset-by-diagnosis interactions were found in the left parietal operculum, left precentral gyrus, bilateral postcentral gyrus, right occipital gyrus, and right orbitofrontal cortex. Post hoc analysis revealed a significant decrease in GMV in all affected regions of EO-ALS patients compared with YCs, with increased GMV in 5 of the 6 brain regions, except for the right orbitofrontal cortex, in LO-ALS patients compared with OCs. LO-ALS patients had a significantly increased GMV than EO-ALS patients after removing the aging effect. Correspondingly, GMV of the left postcentral gyrus correlated with disease severity in the 2 ALS groups. Our findings suggested that the pathological mechanisms in ALS patients with different ages at onset might differ. These findings provide unique insight into the clinical and biological heterogeneity of the 2 ALS subtypes.
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Esclerose Lateral Amiotrófica , Córtex Motor , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/patologia , Imageamento por Ressonância Magnética , Encéfalo/patologia , Córtex Motor/patologiaRESUMO
Background: Malnutrition is associated with poor survival in some diseases. However, the nutritional status in multiple system atrophy (MSA) is unknown, and the significance of malnutrition for the prediction of mortality in MSA has not been well established. Objective: We aimed to determine the prevalence of malnutrition and the prognostic value of malnutrition in patients with early-stage MSA. Methods: Patients diagnosed with early phase MSA (disease duration<3 years) were recruited, and they were followed every year until May 2023. The nutritional status of patients with MSA was assessed using the Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI). Kaplan-Meier survival analysis and Cox regression model were used to assess the prognostic value of malnutrition in MSA. Results: A total of 224 patients with probable MSA (106 MSA died and 118 were still alive) and 213 matched healthy controls (HCs) were enrolled. According to COUNT score and GNRI, patients with MSA had higher prevalence of malnutrition than HCs (44.6% vs. 14.1 and 17.9% vs. 0.9%, respectively). The median survival from symptom onset in patients with MSA in the malnutrition group was shorter than those in the normal-nutrition group (5.98 vs. 7.06 years, p = 0.012) by COUNT score. Additionally, malnutrition increased the risk of mortality in patients with MSA (HR = 1.556, p = 0.030) and MSA-P (HR = 1.973, p = 0.042) by COUNT score. Interpretation: Malnutrition was common in patients with early-stage MSA. Malnutrition increased the risk of mortality in patients with MSA, and early nutritional supplementation should be taken into consideration.
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Objectives: Mutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson's disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations. Methods: A whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life. Results: The prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061-1.194, p < 0.001) and a lower (i.e., worse) Montreal Cognitive Assessment score (OR = 0.830, 95%CI = 0.713-0.967, p = 0.017) were significantly associated with FOG in PD patients with GBA1 mutations. The presence of FOG was significantly associated with the decreased (i.e., worse) score of PD Questionnaire 39 after adjustment for sex, age, disease duration, motor score, and non-motor score (B = 14.981, p = 0.001). Conclusion: FOG is a relatively common disabling symptom in PD patients with GBA1 mutations, which is affected by motor disability and cognitive decline. Quality of life is reduced in patients with FOG and GBA1 mutations.
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BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by Parkinsonism, ataxia, and autonomic nervous failure. Orthostatic hypotension (OH) is the main feature of central vascular autonomic failure in MSA. OBJECTIVE: The study aimed elucidate the effects of OH on cognitive function, disease milestones, and survival. METHODS: A total of 444 patients with clinically established MSA were enrolled. Mild and severe OH were defined as a decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) >20/10 mmHg and SBP/DBP ≥30/15 mmHg, respectively. RESULTS: In this study, 215 MSA patients presented without OH, 88 had mild OH, and 141 had severe OH. The proportion of MSA-C in the severe OH subgroup was significantly higher than that in the subgroup without OH (95/46 vs. 113/102, pâ=â0.021). The UMSARS I score and the frequency of supine hypertension (SH) in patients with OH were significantly higher than those in patients without OH (16.22 vs. 16.89 vs. 14.60, pâ<â0.001; 77/64 vs. 29/59 vs. 32/183, pâ<â0.001). Factors related to the severity of OH included sex (OR, 0.65; pâ=â0.031), onset age (OR, 0.98; pâ=â0.029), and SH (OR, 0.21; pâ<â0.001). The median survival time of patients with severe OH was significantly lower than that of patients without OH (6.79 vs. 8.13 years, pâ=â0.001). Consistently, Cox survival analysis found that compared with patients without OH, patients with severe OH had a significantly increased risk of death (OR, 2.22; pâ<â0.001). CONCLUSION: Our large cohort study of MSA provides additional evidence for the negative impact of severe OH on survival.
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Hipertensão , Hipotensão Ortostática , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Humanos , Atrofia de Múltiplos Sistemas/complicações , Estudos de Coortes , Doença de Parkinson/complicações , Hipertensão/complicações , Hipertensão/epidemiologia , PrognósticoRESUMO
BACKGROUND: Reactive astrogliosis has been demonstrated to have a role in Parkinson's disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)'s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression. METHODS: A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aß), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively. RESULTS: Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (ß: 0.006, 95% CI [0.001-0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (ß: 0.237, 95% CI [0.055-0.419], p = 0.011) and UPDRS-III (ß: 0.676, 95% CI [0.023-1.330], p = 0.043) scores and H&Y stage (ß: 0.098, 95% CI [0.047-0.149], p < 0.001) and faster decrease in MoCA (ß: - 0.501, 95% CI [- 0.768 to - 0.234], p < 0.001) and FAB scores (ß: - 0.358, 95% CI [- 0.587 to - 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001-1.017], p = 0.033). CONCLUSIONS: Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.
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Doença de Parkinson , Humanos , Atividades Cotidianas , Biomarcadores , Progressão da Doença , Proteína Glial Fibrilar Ácida , Filamentos Intermediários , Doença de Parkinson/complicações , Estudos ProspectivosRESUMO
BACKGROUND: The progression of sleep disturbances remains unclear in patients with early multiple system atrophy (MSA). We aimed to explore the frequency, severity, and coexistence of 2-year longitudinal changes of sleep disturbances including REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), and Parkinson's disease-related sleep problems (PD-SP) in early MSA. METHODS: MSA patients with a disease duration < 3 years were enrolled to complete a 2-year follow-up visit. Sleep disturbances including RBD, EDS, and PD-SP were assessed using the RBD Screening Questionnaire, Epworth sleepiness scale, and PD sleep scale-2, respectively. RESULTS: A total of 220 patients with MSA enrolled in the study and 90 patients completed the 2-year follow-up visit. The score of all three sleep disturbances significantly increased over the 2-year follow-up in MSA and MSA with the predominant parkinsonism group (all p < 0.05). The frequency of PD-SP (from 14.5 to 26.7%) and EDS (from 17.7 to 37.8%) was progressively increased (all p < 0.05) except for RBD (from 51.8 to 65.6%, p = 0.152) over the 2-year follow-up in MSA. The frequency of coexistence of two or three sleep disturbances also increased over time. The most common sleep disturbance was RBD, followed by EDS and PD-SP over the 2-year follow-up. CONCLUSIONS: The present study demonstrated that the frequency of different types of sleep disturbances progressively increased except for RBD and the coexistence of two or three sleep disturbances became more common over time in early MSA. Our study suggested that the assessment and management of sleep disturbances should begin early in MSA.
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Distúrbios do Sono por Sonolência Excessiva , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Transtornos do Sono-Vigília , Humanos , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/epidemiologia , Atrofia de Múltiplos Sistemas/diagnóstico , Estudos Prospectivos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/diagnóstico , Transtorno do Comportamento do Sono REM/complicações , Transtorno do Comportamento do Sono REM/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , SonoRESUMO
OBJECTIVES: High visit-to-visit blood pressure variability (BPV) was found to be associated with cognitive decline in the elderly. This study aimed to investigate the impact of visit-to-visit BPV on cognition in patients with early-stage Parkinson's disease (PD). DESIGN: This is a retrospective analysis of a prospective cohort. SETTING AND PARTICIPANTS: A total of 297 patients with early-stage PD (103 mild cognitive impairments [PD-MCI] and 194 normal cognitions [PD-NC] at baseline) were included from the Parkinson's Progression Markers Initiative study. METHODS: Variation independent of mean (VIM) of the first year was used as the indicator of BPV. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Patients were divided into PD-MCI and PD-NC according to the MoCA score at baseline. Longitudinal cerebrospinal fluid (Aß-42, Aß, α-synuclein, neurofilament light protein, tau phosphorylated at the threonine 181 position, total tau, glial fibrillary acidic protein) and serum (neurofilament light protein) biomarkers were assessed. The Bayesian linear growth model was used to evaluate the relationship between baseline BPV and the rate of change in cognition and biomarkers. RESULTS: Higher systolic VIM of the first year was related to a greater rate of decline in MoCA score in the following years in PD-MCI (ß = -.15 [95% CI -.29, -.01]). No association was found between BPV and biomarkers. CONCLUSION AND IMPLICATIONS: Higher systolic VIM predicted a steeper decline in cognitive tests in PD-MCI independently from the mean value of blood pressure, orthostatic hypotension, and supine hypertension.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Idoso , Doença de Parkinson/complicações , Estudos Prospectivos , Pressão Sanguínea , Estudos Retrospectivos , Teorema de Bayes , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/complicações , Biomarcadores/líquido cefalorraquidiano , Proteínas de NeurofilamentosRESUMO
We modified the original Unified Multiple System Atrophy Rating Scale (UMSARS) for remote video-based visits by excluding ocular motor dysfunction, increased tone, and body sway, resulting in a 23-item UMSARS (mUMSARS-23). The mUMSARS-23 demonstrated excellent reliability and strong validity when compared to the original scale, making it a promising tool for conducting video-based virtual assessments in patients with multiple system atrophy.
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BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown. METHODS: To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (Ndiscovery = 2,272, Nreplication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter assay and RT-qPCR were performed to explore the regulatory effect of the target variant. RESULTS: The total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO. CONCLUSIONS: Collective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.
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Esclerose Lateral Amiotrófica , Humanos , Idade de Início , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Povo Asiático , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Distinct doping propagation characteristics between p-doping and n-doping in light-emitting electrochemical cells (LECs) have been highlighted by intensive reports. Typically, there are significant differences in the doping speeds between p-doping and n-doping, with the former exhibiting a sawtooth frontier and the latter displaying a more uniform frontier profile. In addition, experimental observations demonstrate a uniform motion instead of the theoretically suggested accelerated electrochemical doping frontier propagation. Therefore, there is an urgent need to establish a quantitative model that delves into the underlying mechanisms responsible for doping propagation in LECs. In this study, four variables were selected to investigate the detailed mechanism of electrochemical doping propagation: temperature, voltage, and concentrations of salt and solid electrolyte. Fluorescence imaging revealed that the n-doping and p-doping propagations behaved contrarily with increasing temperature and voltage. By numerically fitting the doping propagation frontier, equations were derived to describe the relationship between the speed of electrochemical doping propagation and temperature/voltage. The underlying mechanisms were elucidated, indicating that anions undergo motion through the cooperative effects of electric field drift and concentration diffusion, while cation transport strongly relies on poly(ethylene oxide) (PEO) segmental motions. In other words, the movement of anions within the electrolyte is characterized by a greater degree of freedom, whereas the motion of cations is significantly dependent on the segmental motions of PEO. The resulting equations were well-fitted with experimental data, providing a solid foundation for further theoretical investigations into electrochemical doping in various devices.
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Plasma Alzheimer's disease-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma Alzheimer's disease-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls were included and followed up for 5 years. Plasma phosphorylated tau181 (p-tau181), Aß40, and Aß42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-single-molecule array. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment and Unified Parkinson's Disease Rating Scale part III. Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than healthy controls. APOE-ε4 carriers had lower plasma Aß42 levels and Aß42/Aß40 ratio. The linear mixed-effects models showed that Montreal Cognitive Assessment scores were associated with plasma p-tau181/Aß42 ratio (ß -1.719 [-3.398 to -0.040], p = .045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (ß -0.170 [-0.322 to -0.018], p = .029; ß 0.329 [0.032 to 0.626], p = .030) and APOE-ε4 carriers (ß -0.318 [-0.602 to -0.034], p = .030; ß 0.632 [0.017 to 1.246], p = .046), but not in the noncarriers. Higher baseline plasma Aß40 correlated with faster cognitive decline in total patients (ß -0.007 [-0.015 to -0.0001], p = .047) and faster motor symptoms deterioration in total patients (ß 0.026 [0.010 to 0.041], p = .001) and APOE-ε4 carriers (ß 0.044 [-0.026 to 0.049], p = .020), but not in the noncarriers. The plasma p-tau181/Aß2 ratio monitors the cognitive status of PD. Higher baseline plasma p-tau181 and Aß40 predict faster cognitive decline and motor symptoms deterioration in PD, especially in APOE-ε4 carriers.