Markers of impaired motor and cognitive volition in Parkinson's disease: Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias

Jared T. Hinkle, Kate Perepezko, Liana Isa Shapiro Rosenthal, Kelly Mills, Alexander Pantelyat, Zoltan Mari, Laura Tochen, Jee Yun Bang, Medha Gudavalli, Nadine Yoritomo, Ankur Butala, Catherine C. Bakker, Vanessa Johnson, Emile Moukheiber, Ted M Dawson, Gregory M Pontone

Research output: Contribution to journalArticle

Abstract

Introduction: Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD. Dysregulation of volition characterizes both dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates in a large PD cohort. Methods: We analyzed cross-sectional data from 654 participants collected through the NINDS Parkinson's Disease Biomarkers Program. DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated variables were selected from PD-validated or PD-specific scales of neuropsychiatric or motoric status. Multivariable models with DDS/ICD or dyskinesia presence outcomes were produced with backward stepwise regression to identify factors independently associated with DDS/ICD and/or dyskinesias. Results: Fifty-three (8.1%) participants endorsed DDS and/or ICD symptoms and 150 (22.9%) were dyskinetic. In multivariable analysis, psychosis was independently associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001). Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and high akinesia-rigidity score (p < 0.001) were associated with dyskinesias. Conclusions: Our findings suggest that psychosis may be an important marker of impaired volition across motor and cognitive domains. Unpredictable motor fluctuations, psychosis, and depression may together comprise a phenotypic profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD patients should be closely monitored for psychotic symptoms and treated appropriately.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
DOIs
StateAccepted/In press - Jan 1 2017

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Disruptive, Impulse Control, and Conduct Disorders
Dyskinesias
Parkinson Disease
Dopamine
Psychotic Disorders
National Institute of Neurological Disorders and Stroke
Depression
Movement Disorders
Tremor
Psychiatry
Biomarkers

Keywords

  • DDS
  • Depression
  • Dopamine Dysregulation Syndrome
  • Dyskinesias
  • Hallucinations
  • ICD
  • Impulse control disorders
  • Motor subtypes
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Markers of impaired motor and cognitive volition in Parkinson's disease : Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias. / Hinkle, Jared T.; Perepezko, Kate; Rosenthal, Liana Isa Shapiro; Mills, Kelly; Pantelyat, Alexander; Mari, Zoltan; Tochen, Laura; Bang, Jee Yun; Gudavalli, Medha; Yoritomo, Nadine; Butala, Ankur; Bakker, Catherine C.; Johnson, Vanessa; Moukheiber, Emile; Dawson, Ted M; Pontone, Gregory M.

In: Parkinsonism and Related Disorders, 01.01.2017.

Research output: Contribution to journalArticle

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abstract = "Introduction: Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD. Dysregulation of volition characterizes both dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates in a large PD cohort. Methods: We analyzed cross-sectional data from 654 participants collected through the NINDS Parkinson's Disease Biomarkers Program. DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated variables were selected from PD-validated or PD-specific scales of neuropsychiatric or motoric status. Multivariable models with DDS/ICD or dyskinesia presence outcomes were produced with backward stepwise regression to identify factors independently associated with DDS/ICD and/or dyskinesias. Results: Fifty-three (8.1{\%}) participants endorsed DDS and/or ICD symptoms and 150 (22.9{\%}) were dyskinetic. In multivariable analysis, psychosis was independently associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001). Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and high akinesia-rigidity score (p < 0.001) were associated with dyskinesias. Conclusions: Our findings suggest that psychosis may be an important marker of impaired volition across motor and cognitive domains. Unpredictable motor fluctuations, psychosis, and depression may together comprise a phenotypic profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD patients should be closely monitored for psychotic symptoms and treated appropriately.",
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T1 - Markers of impaired motor and cognitive volition in Parkinson's disease

T2 - Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias

AU - Hinkle, Jared T.

AU - Perepezko, Kate

AU - Rosenthal, Liana Isa Shapiro

AU - Mills, Kelly

AU - Pantelyat, Alexander

AU - Mari, Zoltan

AU - Tochen, Laura

AU - Bang, Jee Yun

AU - Gudavalli, Medha

AU - Yoritomo, Nadine

AU - Butala, Ankur

AU - Bakker, Catherine C.

AU - Johnson, Vanessa

AU - Moukheiber, Emile

AU - Dawson, Ted M

AU - Pontone, Gregory M

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Introduction: Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD. Dysregulation of volition characterizes both dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates in a large PD cohort. Methods: We analyzed cross-sectional data from 654 participants collected through the NINDS Parkinson's Disease Biomarkers Program. DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated variables were selected from PD-validated or PD-specific scales of neuropsychiatric or motoric status. Multivariable models with DDS/ICD or dyskinesia presence outcomes were produced with backward stepwise regression to identify factors independently associated with DDS/ICD and/or dyskinesias. Results: Fifty-three (8.1%) participants endorsed DDS and/or ICD symptoms and 150 (22.9%) were dyskinetic. In multivariable analysis, psychosis was independently associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001). Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and high akinesia-rigidity score (p < 0.001) were associated with dyskinesias. Conclusions: Our findings suggest that psychosis may be an important marker of impaired volition across motor and cognitive domains. Unpredictable motor fluctuations, psychosis, and depression may together comprise a phenotypic profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD patients should be closely monitored for psychotic symptoms and treated appropriately.

AB - Introduction: Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD. Dysregulation of volition characterizes both dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates in a large PD cohort. Methods: We analyzed cross-sectional data from 654 participants collected through the NINDS Parkinson's Disease Biomarkers Program. DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated variables were selected from PD-validated or PD-specific scales of neuropsychiatric or motoric status. Multivariable models with DDS/ICD or dyskinesia presence outcomes were produced with backward stepwise regression to identify factors independently associated with DDS/ICD and/or dyskinesias. Results: Fifty-three (8.1%) participants endorsed DDS and/or ICD symptoms and 150 (22.9%) were dyskinetic. In multivariable analysis, psychosis was independently associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001). Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and high akinesia-rigidity score (p < 0.001) were associated with dyskinesias. Conclusions: Our findings suggest that psychosis may be an important marker of impaired volition across motor and cognitive domains. Unpredictable motor fluctuations, psychosis, and depression may together comprise a phenotypic profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD patients should be closely monitored for psychotic symptoms and treated appropriately.

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KW - Depression

KW - Dopamine Dysregulation Syndrome

KW - Dyskinesias

KW - Hallucinations

KW - ICD

KW - Impulse control disorders

KW - Motor subtypes

KW - Parkinson's disease

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