Longitudinal Monitoring of Parkinson's Disease in Different Ethnic Cohorts: The DodoNA and LONG-PD Study

Μarkopoulou, Κaterina; Aasly, Jan; Chung, Sun Ju; Dardiotis, Efthimios; Wirdefeldt, Karin; Premkumar, Ashvini P.; Schoneburg, Bernadette; Kartha, Ninith; Wilk, Gary; Wei, Jun; Simon, Kelly Claire; Tideman, Samuel; Epshteyn, Alexander; Hadsell, Bryce; Garduño, L. Sergio; Pham, Anna; Frigerio, Roberta; Maraganore, Demetrius M.

doi:10.3389/fneur.2020.00548

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…We hypothesized that SNPs which have been previously demonstrated to show significant associations with PD-risk using large GWAS and low frequency and rare variants at parkinsonism-associated genes identified in the MDSgene database (19) differentially contribute to discrete baseline clinical parameters/symptoms. To test this hypothesis, we evaluated their association in two well-characterized patient cohorts [MEPD (20) and DodoNA (23)] where individual clinical symptoms and objective test scores were obtained at baseline using SCDS tools embedded in the EMR. The findings are presented in the following two sections.…”

Section: Resultsmentioning

confidence: 99%

“…Eight hundred and fifty-six subjects with clinically definite or clinically probably Parkinson's disease (Bower criteria) (21) enrolled in two previously described patient cohorts [Molecular Epidemiology of Parkinson's Disease, MEPD (22), N = 201; DodoNA (23), N = 655] were included in this study. All patients in these cohorts had a diagnosis of PD at study entry and were residents of Cook and Lake Counties in Illinois, USA.…”

Section: Subjects and Clinical Informationmentioning

confidence: 99%

“…Blood samples were collected in the majority of cases at an initial baseline visit or within a 3-month window following the initial visit. Data on clinical parameters were obtained from SCDS developed to standardize clinical assessment and retained within the EMR as described (20,23). Given the community-based practice setting, our cohort included both de novo and previously diagnosed PD patients.…”

Section: Subjects and Clinical Informationmentioning

confidence: 99%

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Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort

et al. 2021

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Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members. We find that in most cases an individual common PD-risk SNP identified in GWAS is associated with only a single clinical feature or test score, while gene-level tests assessing low-frequency and rare variants reveal genes associated in either a unique or partially overlapping manner with the different clinical features and test scores. Protein-protein interaction network analysis of the identified genes reveals that while some of these genes are members of already identified protein networks others are not. These findings indicate that genetic risk factors for PD differentially affect the phenotypic presentation and that genes associated with PD risk are also differentially associated with individual disease phenotypic characteristics at baseline. These findings raise the intriguing possibility that different SNPs/gene effects impact discrete phenotypic characteristics. Furthermore, they support the hypothesis that different gene and protein-protein interaction networks that underlie PD risk, the PD phenotype, and the neurodegenerative process leading to the disease phenotype, and point to the significance of the genetic background on disease phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Subjects and Clinical Informationmentioning

confidence: 99%

Section: Subjects and Clinical Informationmentioning

confidence: 99%

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Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort

et al. 2021

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“…Patient sample collection must conform to governmental and institutional guidelines and consider protocols that will optimize the quantitation and identification of synucleins in biological samples. This includes sample storage temperature, storage time, time before processing (from sample to centrifuge), sample mixing (adding an anti-coagulant), checking for blood contamination, sample storage and delivery (with ice or room temperature, in boxes or not) ( Mollenhauer et al, 2017 ; Markopoulou et al, 2020 ).…”

Section: Mass Spectrometry Identification and Quantification Of Synuc...mentioning

confidence: 99%

Proteomics Challenges for the Assessment of Synuclein Proteoforms as Clinical Biomarkers in Parkinson’s Disease

Pons

Loftus

Vialaret

et al. 2022

Front. Aging Neurosci.

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Parkinson’s disease is a complex neurodegenerative disorder resulting in a multifaceted clinical presentation which includes bradykinesia combined with either rest tremor, rigidity, or both, as well as many non-motor symptoms. The motor features of the disorder are associated with the pathological form of alpha synuclein aggregates and fibrils in Lewy bodies and loss of dopaminergic neurons in the substantia nigra. Parkinson’s disease is increasingly considered as a group of underlying disorders with unique genetic, biological, and molecular abnormalities that are likely to respond differentially to a given therapeutic approach. For this reason, it is clinically challenging to treat and at present, no therapy can slow down or arrest the progression of Parkinson’s disease. There is a clear unmet clinical need to develop reliable diagnostic and prognostic biomarkers. When disease-modifying treatments become available, prognostic biomarkers are required to support a definitive diagnosis and clinical intervention during the long prodromal period as no clinical implications or symptoms are observed. Robust diagnostic biomarkers would also be useful to monitor treatment response. Potential biomarkers for the sporadic form of Parkinson’s disease have mostly included synuclein species (monomer, oligomer, phosphorylated, Lewy Body enriched fraction and isoforms). In this review, we consider the analysis of synuclein and its proteoforms in biological samples using proteomics techniques (immunoassay and mass spectrometry) applied to neurodegenerative disease research.

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“…While MDS-UPDRS subscale scores do not assess specificity of impairments, moderate and statistically significant associations have been reported for the "speech" subscale score or the total MDS-UPDRS motor section score with clinical measures of voice and swallowing function (Kwon & Lee, 2019;Majdinasab et al, 2016;Midi et al, 2008;Skodda et al, 2013). Few studies have reported progressive patterns of self-perceived speech and swallowing scores from the MDS-UPDRS, although evidence from reports of total scores of Section II (where the "speech" and "swallowing" subscale items are rated) support the notion that as PWPD progress through the stages of PD (i.e., based on Hoehn and Yahr scale) the severity levels based on MDS-UPDRS scale scores increase (Hosking et al, 2021;Markopoulou et al, 2020). Due to the ubiquitous use of MDS-UPDRS in clinical and research settings along with its assessment of patient self-perceptions of swallowing and speech impairment, it could be a useful tool to track how self-perceived changes in speech and swallowing occur over time in large samples of PWPD.…”

mentioning

confidence: 99%

Progression of Self-Perceived Speech and Swallowing Impairment in Early Stage Parkinson's Disease: Longitudinal Analysis of the Unified Parkinson's Disease Rating Scale

Zhang

2022

J Speech Lang Hear Res

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Purpose: The purpose of this study was to investigate the presence and progression of self-perceived speech and swallowing impairments in newly diagnosed people with Parkinson's disease (PD) longitudinally across 6 years. Method: Longitudinal data from the Parkinson's Progression Markers Initiative were analyzed across six consecutive years in a cohort of 269 newly diagnosed people with PD, and a subset of those ( n = 211) who were assessed at every time point across the 6 years. Dependent variables included self-perceived ratings of speech and swallowing impairment severity from the Unified Parkinson's Disease Rating Scale. Patient-centered factors of age at diagnosis and motor phenotype were also assessed to determine if they were related to the change in self-perceived speech and swallowing impairments. Results: Overall, self-perceived speech and swallowing impairments were present in newly diagnosed people with PD, although over time, the degree of severity for both remained in the mild range. However, the rate of change over time was significant for perceived speech impairment, F (5.5, 1158.8) = 21.1, p < .001), and perceived swallowing impairment, F (5.2, 1082.6) = 8.6, p < .001. Changes for speech and swallowing impairment were both in the direction of progressive severity. There were no effects of age at diagnosis or motor phenotype on the degree of change for either speech or swallowing. Conclusions: Self-perceptions of speech and swallowing impairment changed significantly over time in newly diagnosed people with PD (PWPD). Consistent with existing literature, self-perceptions of speech impairment were rated as more severe than those of swallowing impairment. These findings reveal that even in the early years postdiagnoses, PWPD are experiencing changes to speech and swallowing function, albeit within the mildly severe range. The presence of self-perceived mild speech and swallowing impairments in the initial years postdiagnosis may support the need for intervention to improve and or sustain function over time.

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Longitudinal Monitoring of Parkinson's Disease in Different Ethnic Cohorts: The DodoNA and LONG-PD Study

Cited by 14 publications

References 22 publications

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort

Proteomics Challenges for the Assessment of Synuclein Proteoforms as Clinical Biomarkers in Parkinson’s Disease

Progression of Self-Perceived Speech and Swallowing Impairment in Early Stage Parkinson's Disease: Longitudinal Analysis of the Unified Parkinson's Disease Rating Scale

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