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 journalArticlepeer-review

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

Bibliographical note

Funding Information:
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.

Funding Information:
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 .

Funding Information:
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 .

Funding Information:
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.

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

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

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