scholarly journals An MRI Atrophy Biomarker Predicts Global Prognosis in Early De Novo Parkinson’s Disease

2019 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
The Other ◽  
Emission Computed Tomography ◽  
Composite Outcome ◽  
Mixed Effect ◽  
Annual Increase ◽  
Potential Biomarker ◽  
Updrs Part

ABSTRACTBackgroundCommonly used neuroimaging biomarkers in Parkinson’s disease (PD) are useful for diagnosis but poor at predicting outcomes. We explored whether an atrophy pattern from whole-brain structural MRI, measured in the drug-naïve early stage, could predict PD prognosis.Methods362 de novo PD patients with T1-weighted MRI (n=222 for the main analysis, 140 for the validation analysis) were recruited from the Parkinson’s Progression Markers Initiative (PPMI). We investigated a previously identified PD-specific network atrophy pattern as a potential biomarker of disease severity and prognosis. Progression trajectories of motor function (MDS-UPDRS-part III), cognition (Montreal Cognitive Assessment (MoCA)), and a global composite outcome measure were compared between atrophy tertiles using mixed effect models. The prognostic value of the MRI atrophy measure was compared with 123I ioflupane single photon emission computed tomography, the postural-instability-gait-disturbance score, and cerebrospinal fluid markers.FindingsAfter 4.5 years follow-up, PD-specific atrophy network score at baseline significantly predicted change in UPDRS-part III (r=-0.197, p=0.003), MoCA (r=0.253, p=0.0002) and global composite outcome (r=-0.249, p=0.0002). Compared with the 3rd tertile (i.e. least atrophy), the tertile with the highest baseline atrophy (i.e. the 1st tertile) had a 3-point annual faster progression in UPDRS-part III (p=0.012), faster worsening of posture-instability gait scores (+0.21 further annual increase, p<0.0001), faster decline in MoCA (−0.74 further annual decline in MoCA, p=0.0372) and a +0.38 (p=0.0029) faster annual increase in the global composite z-score. All findings were replicated in a validation analysis using 1.5T MRI. By comparison, the other biomarkers were limited in their ability to predict prognosis either in the main or validation analysis.InterpretationA PD-specific network atrophy pattern predicts progression of motor, cognitive, and global outcome in PD, and is a stronger predictor of prognosis than any of the other tested biomarkers. Therefore, it has considerable potential as a prognostic biomarker for clinical trials of early PD.

scholarly journals Serum miR-214 Serves as a Biomarker for Prodromal Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Lanting Li ◽  
Jingru Ren ◽  
Chenxi Pan ◽  
Yuqian Li ◽  
Jianxia Xu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Area Under Curve ◽  
Operating Characteristic ◽  
De Novo ◽  
Characteristic Curve ◽  
The Other ◽  
Circulating Micrornas ◽  
Potential Biomarker ◽  
Operating Characteristic Curve

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.

scholarly journals Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

2017 ◽  
Vol 89 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Tanya Simuni ◽  
Chelsea Caspell-Garcia ◽  
Christopher S Coffey ◽  
Daniel Weintraub ◽  
Brit Mollenhauer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
De Novo ◽  
Controlled Study ◽  
Motor Symptoms ◽  
Biological Variables ◽  
Significant Difference ◽  
Non Motor Symptoms ◽  
Updrs Part

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson’s disease (PD) compared with healthy controls (HC).MethodsParkinson’s Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.

scholarly journals Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mayela Rodríguez-Violante ◽  
Amin Cervantes-Arriaga ◽  
Salvador Velázquez-Osuna ◽  
Rodrigo Llorens-Arenas ◽  
Humberto Calderón-Fajardo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychotic Symptom ◽  
Correlation Coefficient ◽  
Neuropsychiatric Symptoms ◽  
Neuropsychiatric Disorders ◽  
The Other ◽  
High Association ◽  
Independent Validation ◽  
Updrs Part

Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD) has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA.Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison.Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was2.9±3.1(range from 0 to 16). The neuropsychiatric MDS-UPDRS part IA score was2.9±3(range from 0 to 14). The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes wasrs=0.93(all,P<0.001).Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.

scholarly journals Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

2020 ◽  
Author(s):  
Fan Zhang ◽  
Qiang Zhao ◽  
Xing Fang ◽  
Meiling Xu ◽  
Jie Tang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features ◽  
De Novo ◽  
Disease Status ◽  
Central China ◽  
Fecal Microbiome ◽  
Potential Biomarker ◽  
Functional Pathways

Abstract Background: Studies have shown that gut microbiota may be involved in the occurrence and progression of Parkinson's disease (PD). Nevertheless, the alterations in fecal microbiome in PD patients from Central China have not been previously investigated, and the way in which these microbes influence PD remain unclear.Methods: We performed metagenomic shotgun analyses to investigate the gut microbiota composition of 46 Central China PD patients and their healthy spouses. The relationships between microbiota and PD clinical features were analyzed, and functional pathways were compared for further understaning the contributions of gut microbiota in PD. We also explored potential biomarker for PD diagnosis.Results: Microbial communities in the feces of PD patients were notably different from those of healthy spouses at species level. Gut microbiota of patients was characterized by depletion of Subdoligranulum_unclassified and Prevotella_copri, while the Bacteroides_stercoris and Escherichia_coli were markedly elevated. Correlation analysis found that most identified species were negatively correlated with disease clinical features. In particular, Prevotella_copri was negatively correlated with age, H-Y stage, UPDRS total score and UPDRS Ⅲ score. Random forest model indicated that 6 species including Prevotella_copri had good predictive value for disease. Functional analyses of the metagenomes revealed differences in microbiota metabolism. Pathways associated with superpathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation, glucose-1-phosphate degradation and methylphosphonate degradation were significant increase in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation and pyrimidine deoxyribonucleosides salvage were significantly decrease. Functional pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle and guanosine ribonucleotides de novo biosynthesis. Conclusion: This study revealed the differences of gut microbiota between PD patients and their healthy spouses. Altered microbiota had correlation with the clinical characteristics of the disease, and maybe used as potential biomarkers for disease status prediction. We also observed differenct functional pathways of gut microbiota in PD patients,which may help to reveal the mechanism of disease occurrence and progression.

scholarly journals Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

2020 ◽  
Author(s):  
Fan Zhang ◽  
Qiang Zhao ◽  
Xing Fang ◽  
Meiling Xu ◽  
Jie Tang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features ◽  
De Novo ◽  
Central China ◽  
Chinese Patients ◽  
Fecal Microbiome ◽  
Potential Biomarker ◽  
Functional Pathways

Abstract Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, pathologic and epidemiologic studies suggest that gut microbiota may play important roles in the occurrence and progression of Parkinson's disease. However, the alterations in fecal microbiome in PD patients from Central China has not been investigated. Therefore, in this case-control study, we characterised the gut microbial community of 46 PD patients and compared it to those of healthy spouses by using metagenomic shotgun sequencing. Correlation between altered microbiota and clinical features were examined, functional pathways of gut microbiota were estimated, and potential biomarker were explored for further understaning of gut microbiota in PD. Results: Microbial communities in the feces of PD patients were notably different from those of healthy spouses at species level. Gut microbiota of patients was characterized by depletion of Prevotella_copri and Bacteroides_fragilis, while the Bacteroides_stercoris and Escherichia_coli were markedly elevated. Correlation analysis found that most identified species were negatively correlated with disease clinical features. In particular, Prevotella_copri was negatively correlated with age and UPDRS Ⅲ score. Random forest model indicated that 6 species including Prevotella_copri had good predictive value for disease. Functional analyses of the metagenomes revealed differences in microbiota metabolism. Pathways associated with superpathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation, glucose-1-phosphate degradation and methylphosphonate degradation were significant increase in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation and pyrimidine deoxyribonucleosides salvage were significantly decrease. Functional pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle and guanosine ribonucleotides de novo biosynthesis. Conclusion: Our findings confirmed changes of gut microbiota in Chinese patients with PD. Altered microbiota had correlation with the clinical characteristics of disease, which may used as potential biomarkers. Different functional pathways of gut microbiota in PD patients will help to improve our understanding of the mechanism in disease, and targeting on gut microbiota may be one of the new therapeutic choices of PD in the future.

Dopaminergic Correlates of Orthostatic Hypotension in de novo Parkinson’s Disease

2020 ◽  
pp. 1-9
Author(s):  
Tadashi Umehara ◽  
Hisayoshi Oka ◽  
Atsuo Nakahara ◽  
Tomotaka Shiraishi ◽  
Takeo Sato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Orthostatic Hypotension ◽  
De Novo ◽  
Single Photon ◽  
Anterior Part ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Dopamine Depletion ◽  
Dat Spect

Background: Orthostatic hypotension (OH) at an early stage of Parkinson’s disease (PD) predicts poor prognosis, which may suggest degeneration of dopaminergic neurons affects sympathetic function, causing OH. Objective: We tested the hypothesis that striatal dopaminergic depletion is associated with OH in PD. Methods: Out of 99 patients with newly diagnosed untreated PD, 81 patients were enrolled according to our selection criteria. All patients underwent head-up tilt-table testing and striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. The association between hemodynamic changes and 123I-FP-CIT uptake was examined. Results: 123I-FP-CIT uptake in the putamen, especially the anterior part and left side, was related not only to motor severity but also to OH. Change in systolic blood pressure correlated negatively with 123I-FP-CIT uptake in bilateral anterior putamen (left: p <  0.01, right: p <  0.05) and left posterior putamen (p <  0.05). Patients with OH had more severe dopamine depletion in left anterior (p = 0.008) and posterior (p = 0.007) putamen at a similar motor severity than did patients without OH even though both groups have similar baseline characteristics. An analysis of asymmetry index showed patients with OH had symmetrically decreased dopamine levels in anterior putamen when compared to those without OH (p = 0.024). Conclusion: OH is closely related to striatal dopamine depletion in PD. This relation may help to account for the prognostic value of OH.

scholarly journals Sex-Related Longitudinal Change of Motor, Non-Motor, and Biological Features in Early Parkinson’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Marina Picillo ◽  
David-Erick LaFontant ◽  
Susan Bressman ◽  
Chelsea Caspell-Garcia ◽  
Christopher Coffey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Longitudinal Change ◽  
Csf Biomarkers ◽  
Longitudinal Changes ◽  
Multiplicative Factor ◽  
Progression Markers ◽  
And Biological Markers ◽  
Updrs Part

Background: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson’s Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. Results: Men experienced greater longitudinal decline in self-reported motor (p <  0.001) and non-motor (p = 0.009) aspects of experiences of daily living, such that men had a yearly increase in MDS-UPDRS part II by a multiplicative factor of 1.27 compared to women at 0.7, while men had a yearly increase in MDS-UPDRS part I by a multiplicative factor of 0.98, compared to women at 0.67. Compared to women, men had more longitudinal progression in clinician-assessed motor features in the ON medication state (p = 0.010) and required higher dopaminergic medication dosages over time (p = 0.014). Time to reach specific disease milestones and longitudinal changes in CSF biomarkers and DaTscanTM uptake were not different by sex. Conclusion: Men showed higher self-assessed motor and non-motor burden of disease, with possible contributions from suboptimal dopaminergic therapeutic response in men. However, motor features of disease evaluated with clinician-based scales in the OFF medication state, as well as biological biomarkers do not show specific sex-related progression patterns.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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