scholarly journals Longitudinal Change of Clinical and Biological Measures in Early Parkinson's Disease: Parkinson's Progression Markers Initiative Cohort

2018 ◽  
Vol 33 (5) ◽  
pp. 771-782 ◽  
Author(s):  
Tanya Simuni ◽  
Andrew Siderowf ◽  
Shirley Lasch ◽  
Chris S. Coffey ◽  
Chelsea Caspell-Garcia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Longitudinal Change ◽  
Progression Markers ◽  
Early Parkinson’S Disease

scholarly journals High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marco J. Russo ◽  
Christina D. Orru ◽  
Luis Concha-Marambio ◽  
Simone Giaisi ◽  
Bradley R. Groveman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Diagnostic Performance ◽  
De Novo ◽  
Alpha Synuclein ◽  
Diagnostic Tools ◽  
Dat Spect ◽  
Progression Markers ◽  
Early Parkinson’S Disease

AbstractAlpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.

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.

scholarly journals Patients with scans without evidence of dopaminergic deficit (SWEDD) do not have early Parkinson’s disease: Analysis of the PPMI data

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246881
Author(s):  
Jeong Won Lee ◽  
Yoo Sung Song ◽  
Hyeyun Kim ◽  
Bon D. Ku ◽  
Won Woo Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Specific Binding ◽  
The Other ◽  
Significant Difference ◽  
Group A ◽  
Progression Markers ◽  
Matched Comparison ◽  
Disease Analysis ◽  
Early Parkinson’S Disease

Background To evaluate whether patients with scans without evidence of dopaminergic deficit (SWEDD) have early Parkinson’s disease (PD). Methods The clinical characteristics, striatal specific binding ratios (SBRs), and the indices of I-123 FP-CIT SPECT images of 50 SWEDD patients, 304 PD patients, and 141 healthy controls were acquired from the Parkinson’s Progression Markers Initiative (PPMI) data and evaluated during a 2-year clinical follow-up period. Results Of the 50 subjects with SWEDD, PD was confirmed in 13 subjects (the PD-SWEDD group), while the remaining 37 subjects had other diseases (the Other-SWEDD group). Striatal SBR values and striatal asymmetry indices of the PD group were significantly different with those of the PD-SWEDD and Other-SWEDD groups at both baseline and after 2 years (p < 0.001). Putaminal SBR values of the PD-SWEDD group were significantly decreased after 2 years (p < 0.05). There was no difference of the SBR values between baseline and after 2 years in the Other-SWEDD group. A baseline MDS-UPDRS III score matched comparison of the PD and PD-SWEDD group was done due to the large difference of the subject numbers. Striatal SBR values and striatal asymmetry indices were significantly different (p < 0.001) between the two groups at both baseline and after 2 years, but there were no significant difference with respect to the MDS-UPDRS III scores after 2 years between the two groups. Conclusion The different SBR values and asymmetry indices between the PD and PD-SWEDD groups at baseline and after 2 years indicate that SWEDD may not be early PD, but rather a different disease entity.

scholarly journals The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Symptom Onset ◽  
Disease Risk ◽  
Age Of Onset ◽  
Sequencing Analysis ◽  
Age Related ◽  
Australian Cohort ◽  
Progression Markers ◽  
Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

Sign in / Sign up

Export Citation Format

Share Document