Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures

Lana M. Chahine; Andrew Siderowf; Janel Barnes; Nicholas Seedorff; Chelsea Caspell-Garcia; Tanya Simuni; Christopher S. Coffey; Douglas Galasko; Brit Mollenhauer; Vanessa Arnedo; Nichole Daegele; Mark Frasier; Caroline Tanner; Karl Kieburtz; Kenneth Marek

doi:10.3233/JPD-181518

Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures

Lana M. Chahine^*, Andrew Siderowf, Janel Barnes, Nicholas Seedorff, Chelsea Caspell-Garcia, Tanya Simuni, Christopher S. Coffey, Douglas Galasko, Brit Mollenhauer, Vanessa Arnedo, Nichole Daegele, Mark Frasier, Caroline Tanner, Karl Kieburtz, Kenneth Marek

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials. Objectives: To examine whether baseline measures and their 1-year change predict longer-term progression in early PD. Methods: Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models. Results: Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β=0.351; 95% CI=0.146, 0.555), male gender (β=3.090; 95% CI=0.310, 5.869), and baseline (β=-0.199; 95% CI=-0.315, -0.082) and 1-year change (β=0.540; 95% CI=0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β=-0.6229; 95% CI=-1.2910, 0.0452), baseline (β=7.232; 95% CI=2.268, 12.195) and 1-year change (β=45.918; 95% CI=35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β=-0.325;95% CI=-0.695, 0.045); predictors in the model accounted for 44.1% of the variance. Conclusions: Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Original language	English (US)
Pages (from-to)	665-679
Number of pages	15
Journal	Journal of Parkinson's disease
Volume	9
Issue number	4
DOIs	https://doi.org/10.3233/JPD-181518
State	Published - 2019

Keywords

Parkinson's disease
biomarkers
disease progression
surrogate endpoint

ASJC Scopus subject areas

Clinical Neurology
Cellular and Molecular Neuroscience

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10.3233/JPD-181518

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Chahine, L. M., Siderowf, A., Barnes, J., Seedorff, N., Caspell-Garcia, C., Simuni, T., Coffey, C. S., Galasko, D., Mollenhauer, B., Arnedo, V., Daegele, N., Frasier, M., Tanner, C., Kieburtz, K., & Marek, K. (2019). Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures. Journal of Parkinson's disease, 9(4), 665-679. https://doi.org/10.3233/JPD-181518

@article{1cafbf04d36a456baa547fe35f037b9e,

title = "Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures",

abstract = "Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials. Objectives: To examine whether baseline measures and their 1-year change predict longer-term progression in early PD. Methods: Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models. Results: Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β=0.351; 95% CI=0.146, 0.555), male gender (β=3.090; 95% CI=0.310, 5.869), and baseline (β=-0.199; 95% CI=-0.315, -0.082) and 1-year change (β=0.540; 95% CI=0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β=-0.6229; 95% CI=-1.2910, 0.0452), baseline (β=7.232; 95% CI=2.268, 12.195) and 1-year change (β=45.918; 95% CI=35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β=-0.325;95% CI=-0.695, 0.045); predictors in the model accounted for 44.1% of the variance. Conclusions: Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.",

keywords = "Parkinson's disease, biomarkers, disease progression, surrogate endpoint",

author = "Chahine, {Lana M.} and Andrew Siderowf and Janel Barnes and Nicholas Seedorff and Chelsea Caspell-Garcia and Tanya Simuni and Coffey, {Christopher S.} and Douglas Galasko and Brit Mollenhauer and Vanessa Arnedo and Nichole Daegele and Mark Frasier and Caroline Tanner and Karl Kieburtz and Kenneth Marek",

note = "Funding Information: Tanya Simuni, MD has served as a consultant received consulting fees from Acadia, Abbvie, Allergan, Anavex, Avid, GE Medical, Eli Lilly and Company, Harbor, Ibsen, IMPAX, Lundbeck, Merz, Inc., the National Parkinson Foundation, Navidea, Pfizer, TEVA Pharmaceuticals, UCB Pharma, Voyager, US World Meds, and the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research; Dr. Simuni has served as a speaker and received an honorarium from Acadia, IMPAX, Lundbeck, TEVA Pharmaceuticals, and UCB Pharma; Dr Simuni is on the Scientific advisory board for Anavex, Sanofi, MJFF. Dr. Simuni sits on the Advisory Board for IMPAX; Dr. Simuni has received research funding from the NINDS, MJFF, NPF, TEVA Pharmaceuticals, Aus- pex, Biotie, Civitas, Acorda, Lundbeck, Neuroderm, NINDS, National Institutes of Health, Northwestern Foundation, and the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research; Dr. Simuni received funding support for educational programs from GE Medical, TEVA, and Lundbeck. Funding Information: Caroline Tanner MD, PhD serves on the Scientific Advisory Boards of the Michael J. Fox Foundation and the National Spasmodic Dysphonia Association as a voluntary consultant, and has provided paid consulting services to Pfizer Pharmaceuticals. She receives grant support from the Michael J. Fox Foundation, the Parkinson{\textquoteright}s Disease Foundation, the Department of Defense and the National Institutes of Health. Funding Information: Full primary author financial disclosure for the previous 12 months: Lana M. Chahine, MD receives research support from the Michael J Fox Foundation, has received travel payment from MJFF to MJFF conferences, is a paid consultant to MJFF, receives research support for a clinical trial sponsored by Voyager Therapeutics, receives research support for a clinical trial sponsored by Biogen, received travel payments from Voyager Therapeutics to Investigator meeting, and receives royalties from Wolters Kluwel (for book authorship). Funding Information: Karl Kieburtz, MD, MPH serves as a con sultant for the National Institutes of Health (NIH, NINDS), Acorda, Astellas Pharma, AstraZeneca, Auspex, Biotie, Britannia, Can-gene, CHDI,Civitas,Clearpoint Strategy Group, Clintrex, Cynapsus, INC Research, IntecIsis, Lilly, Lundbeck, Medavante, Medivation, Melior Discovery, Neuroderm, Neurmedix, Omeros, Otsuka, Pfizer, Pharma2B, Prothena/Neotope/Elan Pharmaceutical, Raptor Pharmaceuticals, Roche/Genentech, Sage Bionetworks, Serina, Stealth Peptides, Synagile, Teikoku Pharma, Titan, Turing Pharmaceuticals, Upsher-Smith, US WorldMeds, Vaccinex, Voyager, and Weston Brain Institute. Dr Kieburtz receives research grants from thr National Institutes of Health (NEI, NINDS, NIA, NICHD), Michael J Fox Foundation, and Teva. Funding Information: Christopher S. Coffey, PhD serves on the scientific advisory board for data safety and monitoring for NINDS and NIA, received a speaker honorarium for presenting a short course at Rho, Inc., is a consultant for ZZ Biotech, LLC, received research support from the Michael J. Fox Foundation, and is supported by NIH/NINDS, U01 NS077352, PI, 10/01/11-09/30/18 (2) NIH/NINDS, U01 NS077108, PI, 10/01/11-09/30/16 (3) NIH/NHLBI, U01 HL091843, PI, 08/01/09-02/28/15 (4) NIH/NHLBI, U01 NS038529, PI, 12/01/09-12/31/13 NIH/NINDS, (5) U01 NS079163, 08/05/2012-07/31/2015 (6) NIH/NINDS, U01 NS082329, 07/15/2013-06/30/2018 (7) NIH/NINDS, U01 NS084495, 09/15/2013-07/31/2018 Douglas Galasko, MD receives research funding from National Institutes of Health (NIH), Michael J. Fox Foundation, and Eli Lilly and Esai. He is a paid Editor for Alzheimer{\textquoteright}s Research and Therapy. He is a consultant for vTv Therapeutics and serves on a DSMB for Prothena. Publisher Copyright: {\textcopyright} 2019 - IOS Press and the authors. All rights reserved.",

year = "2019",

doi = "10.3233/JPD-181518",

language = "English (US)",

volume = "9",

pages = "665--679",

journal = "Journal of Parkinson's Disease",

issn = "1877-7171",

publisher = "IOS Press",

number = "4",

}

Chahine, LM, Siderowf, A, Barnes, J, Seedorff, N, Caspell-Garcia, C, Simuni, T, Coffey, CS, Galasko, D, Mollenhauer, B, Arnedo, V, Daegele, N, Frasier, M, Tanner, C, Kieburtz, K & Marek, K 2019, 'Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures', Journal of Parkinson's disease, vol. 9, no. 4, pp. 665-679. https://doi.org/10.3233/JPD-181518

TY - JOUR

T1 - Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures

AU - Chahine, Lana M.

AU - Siderowf, Andrew

AU - Barnes, Janel

AU - Seedorff, Nicholas

AU - Caspell-Garcia, Chelsea

AU - Simuni, Tanya

AU - Coffey, Christopher S.

AU - Galasko, Douglas

AU - Mollenhauer, Brit

AU - Arnedo, Vanessa

AU - Daegele, Nichole

AU - Frasier, Mark

AU - Tanner, Caroline

AU - Kieburtz, Karl

AU - Marek, Kenneth

N1 - Funding Information: Tanya Simuni, MD has served as a consultant received consulting fees from Acadia, Abbvie, Allergan, Anavex, Avid, GE Medical, Eli Lilly and Company, Harbor, Ibsen, IMPAX, Lundbeck, Merz, Inc., the National Parkinson Foundation, Navidea, Pfizer, TEVA Pharmaceuticals, UCB Pharma, Voyager, US World Meds, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni has served as a speaker and received an honorarium from Acadia, IMPAX, Lundbeck, TEVA Pharmaceuticals, and UCB Pharma; Dr Simuni is on the Scientific advisory board for Anavex, Sanofi, MJFF. Dr. Simuni sits on the Advisory Board for IMPAX; Dr. Simuni has received research funding from the NINDS, MJFF, NPF, TEVA Pharmaceuticals, Aus- pex, Biotie, Civitas, Acorda, Lundbeck, Neuroderm, NINDS, National Institutes of Health, Northwestern Foundation, and the Michael J. Fox Foundation for Parkinson’s Research; Dr. Simuni received funding support for educational programs from GE Medical, TEVA, and Lundbeck. Funding Information: Caroline Tanner MD, PhD serves on the Scientific Advisory Boards of the Michael J. Fox Foundation and the National Spasmodic Dysphonia Association as a voluntary consultant, and has provided paid consulting services to Pfizer Pharmaceuticals. She receives grant support from the Michael J. Fox Foundation, the Parkinson’s Disease Foundation, the Department of Defense and the National Institutes of Health. Funding Information: Full primary author financial disclosure for the previous 12 months: Lana M. Chahine, MD receives research support from the Michael J Fox Foundation, has received travel payment from MJFF to MJFF conferences, is a paid consultant to MJFF, receives research support for a clinical trial sponsored by Voyager Therapeutics, receives research support for a clinical trial sponsored by Biogen, received travel payments from Voyager Therapeutics to Investigator meeting, and receives royalties from Wolters Kluwel (for book authorship). Funding Information: Karl Kieburtz, MD, MPH serves as a con sultant for the National Institutes of Health (NIH, NINDS), Acorda, Astellas Pharma, AstraZeneca, Auspex, Biotie, Britannia, Can-gene, CHDI,Civitas,Clearpoint Strategy Group, Clintrex, Cynapsus, INC Research, IntecIsis, Lilly, Lundbeck, Medavante, Medivation, Melior Discovery, Neuroderm, Neurmedix, Omeros, Otsuka, Pfizer, Pharma2B, Prothena/Neotope/Elan Pharmaceutical, Raptor Pharmaceuticals, Roche/Genentech, Sage Bionetworks, Serina, Stealth Peptides, Synagile, Teikoku Pharma, Titan, Turing Pharmaceuticals, Upsher-Smith, US WorldMeds, Vaccinex, Voyager, and Weston Brain Institute. Dr Kieburtz receives research grants from thr National Institutes of Health (NEI, NINDS, NIA, NICHD), Michael J Fox Foundation, and Teva. Funding Information: Christopher S. Coffey, PhD serves on the scientific advisory board for data safety and monitoring for NINDS and NIA, received a speaker honorarium for presenting a short course at Rho, Inc., is a consultant for ZZ Biotech, LLC, received research support from the Michael J. Fox Foundation, and is supported by NIH/NINDS, U01 NS077352, PI, 10/01/11-09/30/18 (2) NIH/NINDS, U01 NS077108, PI, 10/01/11-09/30/16 (3) NIH/NHLBI, U01 HL091843, PI, 08/01/09-02/28/15 (4) NIH/NHLBI, U01 NS038529, PI, 12/01/09-12/31/13 NIH/NINDS, (5) U01 NS079163, 08/05/2012-07/31/2015 (6) NIH/NINDS, U01 NS082329, 07/15/2013-06/30/2018 (7) NIH/NINDS, U01 NS084495, 09/15/2013-07/31/2018 Douglas Galasko, MD receives research funding from National Institutes of Health (NIH), Michael J. Fox Foundation, and Eli Lilly and Esai. He is a paid Editor for Alzheimer’s Research and Therapy. He is a consultant for vTv Therapeutics and serves on a DSMB for Prothena. Publisher Copyright: © 2019 - IOS Press and the authors. All rights reserved.

PY - 2019

Y1 - 2019

N2 - Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials. Objectives: To examine whether baseline measures and their 1-year change predict longer-term progression in early PD. Methods: Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models. Results: Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β=0.351; 95% CI=0.146, 0.555), male gender (β=3.090; 95% CI=0.310, 5.869), and baseline (β=-0.199; 95% CI=-0.315, -0.082) and 1-year change (β=0.540; 95% CI=0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β=-0.6229; 95% CI=-1.2910, 0.0452), baseline (β=7.232; 95% CI=2.268, 12.195) and 1-year change (β=45.918; 95% CI=35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β=-0.325;95% CI=-0.695, 0.045); predictors in the model accounted for 44.1% of the variance. Conclusions: Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

AB - Improved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials. Objectives: To examine whether baseline measures and their 1-year change predict longer-term progression in early PD. Methods: Parkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models. Results: Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β=0.351; 95% CI=0.146, 0.555), male gender (β=3.090; 95% CI=0.310, 5.869), and baseline (β=-0.199; 95% CI=-0.315, -0.082) and 1-year change (β=0.540; 95% CI=0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β=-0.6229; 95% CI=-1.2910, 0.0452), baseline (β=7.232; 95% CI=2.268, 12.195) and 1-year change (β=45.918; 95% CI=35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β=-0.325;95% CI=-0.695, 0.045); predictors in the model accounted for 44.1% of the variance. Conclusions: Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

KW - Parkinson's disease

KW - biomarkers

KW - disease progression

KW - surrogate endpoint

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U2 - 10.3233/JPD-181518

DO - 10.3233/JPD-181518

M3 - Article

C2 - 31450510

AN - SCOPUS:85073184534

SN - 1877-7171

VL - 9

SP - 665

EP - 679

JO - Journal of Parkinson's Disease

JF - Journal of Parkinson's Disease

IS - 4

ER -

Predicting Progression in Parkinson's Disease Using Baseline and 1-Year Change Measures

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