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1.
Eur J Neurol ; 29(4): 1017-1024, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34951095

RESUMO

BACKGROUND AND PURPOSE: Variants in the glucocerebrosidase (GBA) gene are recognized as a common and important genetic risk factor for Parkinson disease (PD). However, the impact of variant severity on the clinical phenotype of PD in the Chinese population remains unclear. Thus, the present study aimed to determine the frequency of GBA-related PD (GBA-PD) and the relationship of GBA variant severity with clinical characteristics in a large Chinese cohort. METHODS: Long-range polymerase chain reaction and next generation sequencing were performed for the entire GBA gene. GBA variant severity was classified into five classes: mild, severe, risk, complex, and unknown. RESULTS: Among the total 737 PD patients, 47 GBA variants were detected in 79 (10.72%) patients, and the most common GBA variants were R163Q, L444P, and R120W. Complete demographic and clinical data were obtained for 673 patients, which revealed that 18.50% of early onset PD patients had GBA variants. Compared with patients without GBA variants, GBA-PD patients experienced PD onset an average of 4 years earlier and had more severe motor and nonmotor symptoms. Patients carrying severe and complex variants had a higher burden of nonmotor symptoms, especially depression, and more mood/cognitive and gastrointestinal symptoms than patients carrying mild variants. CONCLUSIONS: GBA-PD is highly prevalent in the Chinese population. The severity of GBA variants underlies distinct phenotypic spectrums, with PD patients carrying severe and complex variants seeming to have similar phenotypes. PD patient stratification by GBA variant severity should become a prerequisite for selecting specific treatments.


Assuntos
Glucosilceramidase , Doença de Parkinson , China/epidemiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Glucosilceramidase/genética , Humanos , Mutação/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Prevalência
2.
Neuroscience ; 491: 13-22, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35358647

RESUMO

Although various studies have reported a high prevalence of depression among Parkinson's disease (PD) patients, the pathophysiological mechanism of depression in PD (DPD) is still unclear. The core region of the reward network, the ventral striatum (VS), is critical in the occurrence and development of DPD. This study aimed to explore the altered functional connectivity (FC) of VS subregions in DPD. We recruited 20 DPD patients, 37 non-depressed PD (NDPD) patients, and 41 healthy controls (HC) matched in age, gender, and years of education. The patients' diagnosis with PD was de-novo. We then used resting-state functional magnetic resonance imaging to detect the FC differences of VS subregions among these groups. The FC between the left ventral caudate (vCa_L) and the left middle occipital gyrus (MOG.L) was significantly increased in DPD than in NDPD patients or HC. Compared with HC, NDPD patients exhibited significantly increased FCs between bilateral ventromedial putamen and the left paracentral lobule, the right ventromedial putamen (vmPu_R), and the right precentral gyrus, the vmPu_R, and the left precuneus. Besides, a significant negative correlation was found between the FC values of the vCa_L with the MOG.L and the HAMD-17 scores in the DPD group. The hyperconnectivity between vCa_L and the MOG.L might be viewed as a compensatory mechanism for depression in the early stage of PD. This study provides new insight into the neural mechanism of depression in the early stage of PD and contributes to explore the potential neuroimaging markers for DPD.

3.
Front Neurosci ; 16: 828651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310104

RESUMO

Background: Depression, one of the most frequent non-motor symptoms in Parkinson's disease (PD), was proposed to be related to neural network dysfunction in advanced PD patients. However, the underlying mechanisms in the early stage remain unclear. The study was aimed to explore the alterations of large-scale neural networks in de novo PD patients with depression. Methods: We performed independent component analysis (ICA) on the data of resting-state functional magnetic resonance imaging from 21 de novo PD patients with depression (dPD), 34 de novo PD patients without depression (ndPD), and 43 healthy controls (HCs) to extract functional networks. Intranetwork and internetwork connectivity was calculated for comparison between groups, correlation analysis, and predicting the occurrence of depression in PD. Results: We observed an ordered decrease of connectivity among groups within the ventral attention network (VAN) (dPD < ndPD < HCs), mainly located in the left middle temporal cortex. Besides, dPD patients exhibited hypoconnectivity between the auditory network (AUD) and default mode network (DMN) or VAN compared to ndPD patients or healthy controls. Correlation analysis revealed that depression severity was negatively correlated with connectivity value within VAN and positively correlated with the connectivity value of AUD-VAN in dPD patients, respectively. Further analysis showed that the area under the curve (AUC) for dPD prediction was 0.863 when combining the intranetwork connectivity in VAN and internetwork connectivity in AUD-DMN and AUD-VAN. Conclusion: Our results demonstrated that early dPD may be associated with abnormality of attention bias and especially auditory attention processing. Altered neural network connectivity is expected to be a potential neuroimaging biomarker to predict depression in PD.

4.
J Neurochem ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234288

RESUMO

The use of a diagnostic panel comprising multiple biomarkers has the potential to accurately diagnose Parkinson's disease (PD). However, a panel consisting solely of plasma biomarkers to diagnose PD is not available. This study aimed to examine the diagnostic ability of plasma biomarker panels for de novo PD using novel digital ultrasensitive immunoassay technology. We recruited 45 patients with de novo PD and 20 healthy controls (HCs). The concentrations of plasma α-synuclein (α-syn), amyloid ß-42 (Aß42), Aß40, phosphorylated tau 181 (p-tau181), neurofilament light (NFL), and glial fibrillary acidic protein (GFAP) were quantified using the ultrasensitive single molecule array (Simoa) platform. Patients with de novo PD had higher plasma levels of α-syn and p-tau181 than HCs, adjusting for age and sex. Plasma levels of α-syn and p-tau181 were positively correlated in de novo PD patients. Higher plasma α-syn levels were significantly associated with worse Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor scores, modified Hoehn and Yahr (H-Y) stages, and increased risk of PD with mild cognitive impairment (PD-MCI). Higher plasma p-tau181 concentrations were linked to worse H-Y stages. The diagnostic panel using plasma α-syn and p-tau181, combined with age and sex, showed good performance in discriminating de novo PD patients from HCs (area under the curve = 0.806). These findings suggest that plasma α-syn and p-tau181 together may be a promising diagnostic biomarker panel for de novo PD patients.

5.
CNS Neurosci Ther ; 28(2): 259-268, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34821045

RESUMO

OBJECTIVE: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China. METHODS: The cross-sectional community-based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition. RESULTS: Among the 2,663 dementia-free and Parkinson disease (PD)-free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS-III score (r = -0.456, p = 0.004). CONCLUSION: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.


Assuntos
Disfunção Cognitiva/fisiopatologia , Doença de Parkinson/fisiopatologia , Sintomas Prodrômicos , Idoso , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia
6.
Brain Imaging Behav ; 16(1): 1-10, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33770371

RESUMO

The insula, consisting of functionally diverse subdivisions, plays a significant role in Parkinson's disease (PD)-related cognitive disorders. However, the functional connectivity (FC) patterns of insular subdivisions in PD remain unclear. Our aim is to investigate the changes in FC patterns of insular subdivisions and their relationships with cognitive domains. Three groups of participants were recruited in this study, including PD patients with mild cognitive impairment (PD-MCI, n = 25), PD patients with normal cognition (PD-NC, n = 13), and healthy controls (HCs, n = 17). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in insular subdivisions of the three groups. Moreover, all participants underwent a neuropsychological battery to assess cognition so that the relationship between altered FC and cognitive performance could be elucidated. Compared with the PD-NC group, the PD-MCI group exhibited increased FC between the left dorsal anterior insular (dAI) and the right superior parietal gyrus (SPG), and altered FC was negatively correlated with memory and executive function. Compared with the HC group, the PD-MCI group showed significantly increased FC between the right dAI and the right median cingulate and paracingulate gyri (DCG), and altered FC was positively related to attention/working memory, visuospatial function, and language. Our findings highlighted the different abnormal FC patterns of insular subdivisions in PD patients with different cognitive abilities. Furthermore, dysfunction of the dAI may partly contribute to the decline in executive function and memory in early drug-naïve PD patients.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Parkinson , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Doença de Parkinson/diagnóstico por imagem
7.
Front Neurosci ; 15: 761817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899165

RESUMO

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson's disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI. Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC). Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115-1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009-1.119, p = 0.016). Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.

8.
Front Aging Neurosci ; 13: 700959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776924

RESUMO

Circulating microRNAs (miRNAs) have been proposed to be accessible biomarkers for Parkinson's disease (PD). However, there is a lack of known miRNAs that can serve as biomarkers for prodromal PD (pPD). We previously identified that miR-31 and miR-214 were dysregulated in PD. The aim of this study was to explore the roles of miR-31 and miR-214 in pPD. We recruited 25 pPD patients, 20 patients with de novo PD (dnPD), 24 advanced PD (aPD) patients and 21 controls. Next, we investigated the expression of miR-31 and miR-214. Compared to controls, miR-214 was found to be significantly upregulated in pPD patients while miR-31 was significantly upregulated in aPD patients. In addition, the expression of miR-214 was lower in aPD patients compared to both dnPD or pPD patients, while the expression of miR-31 was higher in aPD patients compared to dnPD patients. In order to predict pPD via miRNA expression, the receiver operating characteristic curve was constructed and the area under curve (AUC) was calculated. For pPD prediction by miR-214, the AUC was 0.756. The optimal cut-off value of miR-214 was 0.1962, and the sensitivity and specificity were 72.0% and 76.2%, respectively. On the other hand, the AUC for aPD detection by miR-31 was 0.744. The optimal cut-off value for miR-31 was 0.0148, with a sensitivity of 87.5% and a specificity of 71.4%. In conclusion, miR-214 can distinguish pPD patients from controls and may be used as a potential biomarker for pPD diagnosis.

9.
Front Neurosci ; 15: 637896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732106

RESUMO

OBJECTIVE: Patients with Parkinson's disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability. METHODS: This study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TD S /mixed S /akinetic-rigid S (ARS), or TD K /mixed K /AR K at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen's kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann-Whitney U-test or Chi-squared test. RESULTS: Of 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κ S = 0.383 ± 0.044, κ K = 0.360 ± 0.042, κ SK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype. CONCLUSION: Fair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.

10.
Front Aging Neurosci ; 13: 789785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35237143

RESUMO

BACKGROUND: Depression is one of the most prevalent and disturbing non-motor symptoms in Parkinson's disease (PD), with few dynamic functional connectivity (dFC) features measured in previous studies. Our aim was to investigate the alterations of the dynamics in de novo patients with PD with depression (dPD). METHODS: We performed dFC analysis on the data of resting-state functional MRI from 21 de novo dPD, 34 de novo patients with PD without depression (ndPD), and 43 healthy controls (HCs). Group independent component analysis, a sliding window approach, followed by k-means clustering were conducted to assess functional connectivity states (which represented highly structured connectivity patterns reoccurring over time) and temporal properties for comparison between groups. We further performed dynamic graph-theoretical analysis to examine the variability of topological metrics. RESULTS: Four distinct functional connectivity states were clustered via dFC analysis. Compared to patients with ndPD and HCs, patients with dPD showed increased fractional time and mean dwell time in state 2, characterized by default mode network (DMN)-dominated and cognitive executive network (CEN)-disconnected patterns. Besides, compared to HCs, patients with dPD and patients with ndPD both showed weaker dynamic connectivity within the sensorimotor network (SMN) in state 4, a regionally densely connected state. We additionally observed that patients with dPD presented less variability in the local efficiency of the network. CONCLUSIONS: Our study demonstrated that altered network connection over time, mainly involving the DMN and CEN, with abnormal dynamic graph properties, may contribute to the presence of depression in patients with PD.

11.
Neuropsychiatr Dis Treat ; 16: 2605-2612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173298

RESUMO

BACKGROUND AND PURPOSE: Little is known about non-motor symptoms (NMSs) associated with the postural instability and gait difficulty (PIGD) phenotype, especially in de novo Parkinson's disease (PD) patients. The aims of this study were to compare NMSs between the tremor dominant (TD) and PIGD phenotypes in de novo PD patients and to determine factors that are associated with the PIGD subtype. PATIENTS AND METHODS: In a cross-sectional study conducted at our single center, 226 de novo PD patients with a median disease duration of 2 years were recruited. Data, including comprehensive demographics, motor subtypes and NMSs were obtained. Motor subtypes were classified as PIGD and non-PIGD (TD and indeterminate) by Jankovic's method. NMSs were evaluated by the non-motor symptoms questionnaire (NMSQuest). RESULTS: We identified 73 (32.3%), 34 (15.0%) and 119 (52.7%) patients with TD, intermediate and PIGD subtypes, respectively. Patients with the PIGD subtype had poorer ADL, motor, depression, anxiety, sleep, and non-motor scores compared with those with the TD subtype. In the NMSQuest, the prevalence of cardiovascular, sleep, mood/cognitive and miscellaneous domains was increased in patients with the PIGD subtype compared with patients with the TD subtype. Multivariable forward stepwise logistic regression revealed that the Hamilton Depression Scale (HAMD) [odds ratio (OR), 1.059; 95% confidence interval (CI), 1.016-1.104, p = 0.007] and pain (OR, 3.175; 95% CI, 1.695-5.947, p < 0.001) exhibit significant discriminative power in differentiating PIGD and non-PIGD groups. CONCLUSION: The PIGD group had more severe cardiovascular symptoms, sleep impairments, mood disturbances and pain. We demonstrated for the first time that pain was associated with the PIGD phenotype. Prompt detection and early treatment of NMSs related to the PIGD phenotype may improve patient outcomes.

12.
Front Neurol ; 11: 601225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33424750

RESUMO

Objective: The aims of this study were to compare the characteristics of three motor subtype classifications in patients with de novo Parkinson's disease (PD) and to find the most suitable motor subtype classification for identifying non-motor symptoms (NMSs). Methods: According to previous studies, a total of 256 patients with de novo PD were classified using the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR), TD/indeterminate/postural instability and gait disturbance (PIGD), and predominantly TD/predominantly PIGD (p-TD/p-PIGD) classification systems. Results: Among the TD/mixed/AR subgroups, the patients with the AR subtype obtained more severe motor scores than the patients with the TD subtype. Among the TD/indeterminate/PIGD subgroups and between the p-TD and p-PIGD subgroups, the patients with the PIGD/p-PIGD subtype obtained more severe scores related to activities of daily living (ADL), motor and non-motor symptoms, including depression, anxiety, and sleep impairment, than the patients with the TD/p-TD subtype. Furthermore, symptoms in the cardiovascular, gastrointestinal, and miscellaneous domains of the Non-motor Questionnaire (NMSQuest) were more prevalent in the patients with the PIGD/p-PIGD subtypes than the patients with the TD/p-TD subtypes. Conclusions: The PIGD/p-PIGD subtypes had more severe ADL, motor and non-motor symptoms than the TD/p-TD subtypes. We disclosed for the first time that the TD/indeterminate/PIGD classification seems to be the most suitable classification among the three motor subtype classifications for identifying NMSs in PD.

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