The Parkinson Progression Marker Initiative (PPMI)

Marek, Kenneth; Jennings, Danna; Lasch, Shirley; Siderowf, Andrew; Tanner, Caroline M.; Simuni, Tanya; Coffey, Chris; Kieburtz, Karl; Flagg, Emily; Chowdhury, Sohini; Poewe, Werner; Mollenhauer, Brit; Klinik, Paracelsus-Elena; Sherer, Todd; Frasier, Mark; Meunier, Claire C.; Rudolph, Alice; Casaceli, Cindy; Seibyl, John; Mendick, Susan; Schuff, Norbert; Zhang, Ying; Toga, Arthur W.; Crawford, Karen; Ansbach, Alison B.; Blasio, Pasquale De; Piovella, Michele; Trojanowski, John Q.; Shaw, Les; Singleton, Andrew; Hawkins, Keith; Eberling, Jamie L.; Brooks, Deborah W.; Russell, David; Leary, Laura; Factor, Stewart A.; Sommerfeld, Barbara; Hogarth, Penelope; Pighetti, Emily; Williams, Karen; Standaert, David G.; Guthrie, Stephanie; Hauser, Robert A.; Delgado, Holly; Jankovic, Joseph; Hunter, Christine; Stern, Matthew B.; Tran, Baochan; Leverenz, James B.; Baca, Marne; Frank, Sam; Thomas, Cathi‐Ann; Richard, Irene Hegeman; Deeley, Cheryl; Rees, Linda; Sprenger, Fabienne; Lang, Elisabeth; Shill, Holly A.; Obradov, S; Fernandez, Hubert; Winters, Adrienna; Berg, Daniela; Gauss, Katharina; Galasko, Douglas; Fontaine, Deborah; Mari, Zoltán; Gerstenhaber, Melissa; Brooks, David J.; Malloy, Sophie; Barone, Paolo; Longo, Katia; Comery, Tom; Ravina, Bernard; Grachev, Igor D.; Gallagher, Kim P.; Collins, Michelle; Widnell, Katherine L.; Ostrowizki, Suzanne; Fontoura, Paulo; Ho, Tony W.; Luthman, Johan; Brug, Marcel van der; Reith, Alastair D.; Taylor, Peggy

doi:10.1016/j.pneurobio.2011.09.005

Cited by 1,435 publications

(890 citation statements)

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“…At baseline, the PD participants were required to (1) have a recent idiopathic PD diagnosis, (2) be untreated for PD, (3) have DAT deficit, and (4) not have dementia as determined by the site investigator. The aims, methodology, and scope of activities of the study have been previously published 7. The study was approved by the institutional review boards at each site, and the participants provided written informed consent.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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Objective: The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD. Methods: We describe 5‐year longitudinal change of the MDS‐UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123‐I Ioflupane striatal binding and correlation between the 2 measures. Results: A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS‐UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for the change over time), with a steeper change in year 1. Dopaminergic therapy had a significant effect on the change of MDS‐UPDRS. There was a significant longitudinal change in dopamine transporter binding in all striatal regions (P < .001). There was a significant but weak correlation between MDS‐UPDRS and dopamine transporter binding at baseline and years 1, 2, and 4, but no correlation between the rate of change of the 2 variables. Conclusions: We present 5‐year longitudinal data on the change of the MDS‐UPDRS and other clinical and dopamine transporter imaging outcome measures in early PD. These data can be used for sample size estimates for interventional studies in the de novo PD population. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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“…PPMI is an ongoing multi‐center project aimed at identifying biomarkers of PD through the longitudinal tracking of standardized clinical, imaging, and biometric assessments across 21 sites (16 US and five European sites) (Parkinson Progression Markers Initiative, 2011). PPMI follows the progression of 423 PD subjects who were newly diagnosed (<6 months) and not on antiparkinsonian medication at enrollment, as well as 196 age‐ and sex‐matched OHC subjects.…”

Section: Methodsmentioning

confidence: 99%

Altered resting‐state functional connectivity of the putamen and internal globus pallidus is related to speech impairment in Parkinson's disease

et al. 2018

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IntroductionSpeech impairment in Parkinson's disease (PD) is pervasive, with life‐impacting consequences. Yet, little is known about how functional connections between the basal ganglia and cortex relate to PD speech impairment (PDSI). Whole‐brain resting‐state connectivity analyses of basal ganglia nuclei can expand the understanding of PDSI pathophysiology.MethodsResting‐state data from 89 right‐handed subjects were downloaded from the Parkinson's Progression Markers Initiative database. Subjects included 12 older healthy controls (“OHC”), 42 PD patients without speech impairment (“PDN”), and 35 PD subjects with speech impairment (“PDSI”). Subjects were assigned to PDN and PDSI groups based on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III speech item scores (“0” vs. “1–4”). Whole‐brain functional connectivity was calculated for four basal ganglia seeds in each hemisphere: putamen, caudate, external globus pallidus (GPe), and internal globus pallidus (GPi). For each seed region, group‐averaged connectivity maps were compared among OHC, PDN, and PDSI groups using a multivariate ANCOVA controlling for the effects of age and sex. Subsequent planned pairwise t‐tests were performed to determine differences between the three groups using a voxel‐wise threshold of p < 0.001 and cluster‐extent threshold of 272 mm3 (FWE<0.05).ResultsIn comparison with OHCs, both PDN and PDSI groups demonstrated significant differences in cortical connectivity with bilateral putamen, bilateral GPe, and right caudate. Compared to the PDN group, the PDSI subjects demonstrated significant differences in cortical connectivity with left putamen and left GPi. PDSI subjects had lower connectivity between the left putamen and left superior temporal gyrus compared to PDN. In addition, PDSI subjects had greater connectivity between left GPi and three cortical regions: left dorsal premotor/laryngeal motor cortex, left angular gyrus, and right angular gyrus.ConclusionsThe present findings suggest that speech impairment in PD is associated with altered cortical connectivity with left putamen and left GPi.

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“…The Parkinson's Progression Markers Initiative (PPMI) is an observational, international, multicenter study designed to establish biomarker‐defined cohorts, identify PD progression biomarkers to improve understanding of disease etiology and course, and to provide the necessary tools to enhance the likelihood of success of PD disease‐modifying therapeutic trials (ClinicalTrials.gov Identifier: NCT01141023). PPMI is a collaborative effort of PD researchers with expertise in biomarker development, PD clinical study design and implementation, bioinformatics, statistics, and data management 3. The study is a public‐private partnership of academic researchers, The Michael J.…”

Section: Introductionmentioning

confidence: 99%

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Marek

Chowdhury

Siderowf

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease‐modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS‐UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α‐synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t‐tau (45/53) and p‐tau (16/18) were reduced in PD versus HC (P < 0.01),Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

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The Parkinson Progression Marker Initiative (PPMI)

Cited by 1,435 publications

References 41 publications

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

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

Altered resting‐state functional connectivity of the putamen and internal globus pallidus is related to speech impairment in Parkinson's disease

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

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