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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)178-183
Number of pages6
JournalParkinsonism and Related Disorders
Volume65
DOIs
StatePublished - Aug 2019

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Tremor
Phenotype
Gait
Dopamine Agents
Disease Progression
Chi-Square Distribution
Biomarkers

Keywords

  • Levodopa
  • Motor phenotype
  • Parkinson's disease
  • Subtypes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Luo, L., Andrews, H., Alcalay, R. N., Poyraz, F. C., Boehme, A. K., Goldman, J. G., ... 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

Motor phenotype classification in moderate to advanced PD in BioFIND study. / Luo, Lan; Andrews, Howard; Alcalay, Roy N.; Poyraz, Fernanda Carvalho; Boehme, Amelia K.; Goldman, Jennifer G.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Sutherland, Margaret; Kopil, Catherine; Naito, Anna; Kang, Un Jung.

In: Parkinsonism and Related Disorders, Vol. 65, 08.2019, p. 178-183.

Research output: Contribution to journalArticle

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
Luo, Lan ; Andrews, Howard ; Alcalay, Roy N. ; Poyraz, Fernanda Carvalho ; Boehme, Amelia K. ; Goldman, Jennifer G. ; Xie, Tao ; Tuite, Paul ; Henchcliffe, Claire ; Hogarth, Penelope ; Amara, Amy W. ; Frank, Samuel ; Sutherland, Margaret ; Kopil, Catherine ; Naito, Anna ; Kang, Un Jung. / Motor phenotype classification in moderate to advanced PD in BioFIND study. In: Parkinsonism and Related Disorders. 2019 ; Vol. 65. pp. 178-183.
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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.",
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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

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KW - Parkinson's disease

KW - Subtypes

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