Motor phenotype classification in moderate to advanced PD in BioFIND study

Lan Luo; Howard Andrews; Roy N. Alcalay; Fernanda Carvalho Poyraz; Amelia K. Boehme; Jennifer G. Goldman; Tao Xie; Paul Tuite; Claire Henchcliffe; Penelope Hogarth; Amy W. Amara; Samuel Frank; Margaret Sutherland; Catherine Kopil; Anna Naito; Un Jung Kang

doi:10.1016/j.parkreldis.2019.06.017

Motor phenotype classification in moderate to advanced PD in BioFIND study

Lan Luo^*, Howard Andrews, Roy N. Alcalay, Fernanda Carvalho Poyraz, Amelia K. Boehme, Jennifer G. Goldman, Tao Xie, Paul Tuite, Claire Henchcliffe, Penelope Hogarth, Amy W. Amara, Samuel Frank, Margaret Sutherland, Catherine Kopil, Anna Naito, Un Jung Kang

^*Corresponding author for this work

Physical Medicine and Rehabilitation

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

21 Scopus citations

Abstract

Background: Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established. Methods: To evaluate motor subtype ratio changes, we used the chi-square test for the off and on state motor subtypes for 115 PD participants in the BioFIND study and used repeated-measures analyses to evaluate longitudinal changes in 162 PD participants with five-year follow-up in the PPMI study. Results: PIGD and TD subtypes in moderate to advanced PD participants change with dopaminergic agents. For those who shifted subtypes, improvement in tremor accounted for the transition of 15 (25.4%) TD participants, while the lack of tremor improvement along with minimal changes in PIGD score resulted in changes for eight (19.0%) PIGD individuals. Analyses of PPMI data revealed that all three subgroups had a significant decrease in subtype ratio with disease progression and a significant decline in subtype ratio occurred only in the TD subgroup with dopaminergic agents. The impact of dopaminergic medication effect on subtype shift for each visit was also more notable with disease advancement. Conclusions: Motor subtypes are not fixed but change with progression of the disease and with treatment. Improvement in tremor was the main contributor to motor phenotype transitions in the BioFIND cohort. A more stable classification system for subtypes based on underlying biological differences is desirable.

Original language	English (US)
Pages (from-to)	178-183
Number of pages	6
Journal	Parkinsonism and Related Disorders
Volume	65
DOIs	https://doi.org/10.1016/j.parkreldis.2019.06.017
State	Published - Aug 2019

Funding

Parts of the data used in the preparation of this article were obtained from the Fox Investigation for New Discovery of Biomarkers (“BioFIND”) database ( http://biofind.loni.usc.edu/ ). For up-to-date information on the study, visit www.michaeljfox.org/biofind . BioFIND is sponsored by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) with support from the National Institute of Neurological Disorders and Stroke . Parts of the data used in the preparation of this article were obtained from the PPMI database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.PPMI-info.org . PPMI—a public-private partnership—is funded by MJFF and funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GalaxoSmithKline, Lily, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, and UCB found at www.ppmi-info.org/fundingpartners . The BioFIND study funding was provided by The Michael J. Fox Foundation for Parkinson's Research and National Institute of Neurological Disorders and Stroke . The National Center for Advancing Translational Sciences of the National Institutes of Health at Columbia University ( UL1TR000040 ) and Oregon Health & Science University ( UL1TR000128 ) provided research visit space support. Fellowship funding for Dr. Luo was provided by the Parkinson's Foundation and the National Institutes of Health Training Grant T32-NS07153 . The BioFIND study funding was provided by The Michael J. Fox Foundation for Parkinson's Research and National Institute of Neurological Disorders and Stroke. The National Center for Advancing Translational Sciences of the National Institutes of Health at Columbia University (UL1TR000040) and Oregon Health & Science University (UL1TR000128) provided research visit space support. Fellowship funding for Dr. Luo was provided by the Parkinson's Foundation and the National Institutes of Health Training Grant T32-NS07153.We would like to thank Dr. Changyu Shen of Harvard Catalyst for his biostatistical help and the PPMI and BioFIND study teams and the volunteers who participated in the study. Parts of the data used in the preparation of this article were obtained from the Fox Investigation for New Discovery of Biomarkers (“BioFIND”) database (http://biofind.loni.usc.edu/). For up-to-date information on the study, visit www.michaeljfox.org/biofind. BioFIND is sponsored by The Michael J. Fox Foundation for Parkinson's Research (MJFF) with support from the National Institute of Neurological Disorders and Stroke. Parts of the data used in the preparation of this article were obtained from the PPMI database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.PPMI-info.org. PPMI—a public-private partnership—is funded by MJFF and funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GalaxoSmithKline, Lily, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, and UCB found at www.ppmi-info.org/fundingpartners.

Keywords

Levodopa
Motor phenotype
Parkinson's disease
Subtypes

ASJC Scopus subject areas

Neurology
Geriatrics and Gerontology
Clinical Neurology

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10.1016/j.parkreldis.2019.06.017

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Luo, L., Andrews, H., Alcalay, R. N., Poyraz, F. C., Boehme, A. K., Goldman, J. G., Xie, T., Tuite, P., Henchcliffe, C., Hogarth, P., Amara, A. W., Frank, S., Sutherland, M., Kopil, C., Naito, A., & Kang, U. J. (2019). Motor phenotype classification in moderate to advanced PD in BioFIND study. Parkinsonism and Related Disorders, 65, 178-183. https://doi.org/10.1016/j.parkreldis.2019.06.017

@article{267aadf3e3414a68a37742e8ced2500a,

title = "Motor phenotype classification in moderate to advanced PD in BioFIND study",

abstract = "Background: Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established. Methods: To evaluate motor subtype ratio changes, we used the chi-square test for the off and on state motor subtypes for 115 PD participants in the BioFIND study and used repeated-measures analyses to evaluate longitudinal changes in 162 PD participants with five-year follow-up in the PPMI study. Results: PIGD and TD subtypes in moderate to advanced PD participants change with dopaminergic agents. For those who shifted subtypes, improvement in tremor accounted for the transition of 15 (25.4%) TD participants, while the lack of tremor improvement along with minimal changes in PIGD score resulted in changes for eight (19.0%) PIGD individuals. Analyses of PPMI data revealed that all three subgroups had a significant decrease in subtype ratio with disease progression and a significant decline in subtype ratio occurred only in the TD subgroup with dopaminergic agents. The impact of dopaminergic medication effect on subtype shift for each visit was also more notable with disease advancement. Conclusions: Motor subtypes are not fixed but change with progression of the disease and with treatment. Improvement in tremor was the main contributor to motor phenotype transitions in the BioFIND cohort. A more stable classification system for subtypes based on underlying biological differences is desirable.",

keywords = "Levodopa, Motor phenotype, Parkinson's disease, Subtypes",

author = "Lan Luo and Howard Andrews and Alcalay, {Roy N.} and Poyraz, {Fernanda Carvalho} and Boehme, {Amelia K.} and Goldman, {Jennifer G.} and Tao Xie and Paul Tuite and Claire Henchcliffe and Penelope Hogarth and Amara, {Amy W.} and Samuel Frank and Margaret Sutherland and Catherine Kopil and Anna Naito and Kang, {Un Jung}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = aug,

doi = "10.1016/j.parkreldis.2019.06.017",

language = "English (US)",

volume = "65",

pages = "178--183",

journal = "Parkinsonism and Related Disorders",

issn = "1353-8020",

publisher = "Elsevier Ltd",

}

Luo, L, Andrews, H, Alcalay, RN, Poyraz, FC, Boehme, AK, Goldman, JG, Xie, T, Tuite, P, Henchcliffe, C, Hogarth, P, Amara, AW, Frank, S, Sutherland, M, Kopil, C, Naito, A & Kang, UJ 2019, 'Motor phenotype classification in moderate to advanced PD in BioFIND study', Parkinsonism and Related Disorders, vol. 65, pp. 178-183. https://doi.org/10.1016/j.parkreldis.2019.06.017

TY - JOUR

T1 - Motor phenotype classification in moderate to advanced PD in BioFIND study

AU - Luo, Lan

AU - Andrews, Howard

AU - Alcalay, Roy N.

AU - Poyraz, Fernanda Carvalho

AU - Boehme, Amelia K.

AU - Goldman, Jennifer G.

AU - Xie, Tao

AU - Tuite, Paul

AU - Henchcliffe, Claire

AU - Hogarth, Penelope

AU - Amara, Amy W.

AU - Frank, Samuel

AU - Sutherland, Margaret

AU - Kopil, Catherine

AU - Naito, Anna

AU - Kang, Un Jung

PY - 2019/8

Y1 - 2019/8

N2 - Background: Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established. Methods: To evaluate motor subtype ratio changes, we used the chi-square test for the off and on state motor subtypes for 115 PD participants in the BioFIND study and used repeated-measures analyses to evaluate longitudinal changes in 162 PD participants with five-year follow-up in the PPMI study. Results: PIGD and TD subtypes in moderate to advanced PD participants change with dopaminergic agents. For those who shifted subtypes, improvement in tremor accounted for the transition of 15 (25.4%) TD participants, while the lack of tremor improvement along with minimal changes in PIGD score resulted in changes for eight (19.0%) PIGD individuals. Analyses of PPMI data revealed that all three subgroups had a significant decrease in subtype ratio with disease progression and a significant decline in subtype ratio occurred only in the TD subgroup with dopaminergic agents. The impact of dopaminergic medication effect on subtype shift for each visit was also more notable with disease advancement. Conclusions: Motor subtypes are not fixed but change with progression of the disease and with treatment. Improvement in tremor was the main contributor to motor phenotype transitions in the BioFIND cohort. A more stable classification system for subtypes based on underlying biological differences is desirable.

AB - Background: Three motor phenotypes have been described in PD: postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype. These phenotypes have been associated with different cognitive trajectories, motor outcomes, and biomarkers profiles. However, whether motor subtype classifications change with treatment and disease progression is not well established. Methods: To evaluate motor subtype ratio changes, we used the chi-square test for the off and on state motor subtypes for 115 PD participants in the BioFIND study and used repeated-measures analyses to evaluate longitudinal changes in 162 PD participants with five-year follow-up in the PPMI study. Results: PIGD and TD subtypes in moderate to advanced PD participants change with dopaminergic agents. For those who shifted subtypes, improvement in tremor accounted for the transition of 15 (25.4%) TD participants, while the lack of tremor improvement along with minimal changes in PIGD score resulted in changes for eight (19.0%) PIGD individuals. Analyses of PPMI data revealed that all three subgroups had a significant decrease in subtype ratio with disease progression and a significant decline in subtype ratio occurred only in the TD subgroup with dopaminergic agents. The impact of dopaminergic medication effect on subtype shift for each visit was also more notable with disease advancement. Conclusions: Motor subtypes are not fixed but change with progression of the disease and with treatment. Improvement in tremor was the main contributor to motor phenotype transitions in the BioFIND cohort. A more stable classification system for subtypes based on underlying biological differences is desirable.

KW - Levodopa

KW - Motor phenotype

KW - Parkinson's disease

KW - Subtypes

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C2 - 31255537

AN - SCOPUS:85067965209

SN - 1353-8020

VL - 65

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EP - 183

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

ER -

Motor phenotype classification in moderate to advanced PD in BioFIND study

Abstract

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Keywords

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