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

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/psych...

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Published inParkinsonism & related disorders Vol. 47; pp. 50 - 56
Main Authors Hinkle, Jared T., Perepezko, Kate, Rosenthal, Liana S., Mills, Kelly A., 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.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.02.2018
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Abstract 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. 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. 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. 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. •In PD, dyskinesias and DDS or ICD may have analogous pathophysiologies.•Shared correlates of dyskinesias, DDS, and ICD were investigated.•Psychosis was a prominent marker of both dyskinesias and DDS/ICD.•Depression and complex motor fluctuations were associated with DDS/ICD.•High akinesia-rigidity—but low tremor—impairment was associated with dyskinesias.
AbstractList 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. 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. 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. 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.
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. 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. 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. 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. •In PD, dyskinesias and DDS or ICD may have analogous pathophysiologies.•Shared correlates of dyskinesias, DDS, and ICD were investigated.•Psychosis was a prominent marker of both dyskinesias and DDS/ICD.•Depression and complex motor fluctuations were associated with DDS/ICD.•High akinesia-rigidity—but low tremor—impairment was associated with dyskinesias.
INTRODUCTIONDopaminergic 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.METHODSWe 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.RESULTSFifty-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.CONCLUSIONSOur 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.
Author Butala, Ankur
Pontone, Gregory M.
Mills, Kelly A.
Yoritomo, Nadine
Hinkle, Jared T.
Gudavalli, Medha
Rosenthal, Liana S.
Pantelyat, Alexander
Tochen, Laura
Bang, Jee Yun
Bakker, Catherine C.
Perepezko, Kate
Mari, Zoltan
Moukheiber, Emile
Dawson, Ted M.
Johnson, Vanessa
AuthorAffiliation 7 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
5 Dept. of Neurology, Children’s National Medical Center, 111 Michigan Avenue, NW, Washington, DC, United States
8 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
1 Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States
4 Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, United States
2 Dept. of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
3 Morris K. Udall Parkinson’s Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
6 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Keywords Dyskinesias
DDS
Motor subtypes
Parkinson's disease
Impulse control disorders
Hallucinations
Depression
ICD
Dopamine Dysregulation Syndrome
Language English
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SSID ssj0007503
Score 2.332114
Snippet Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the...
INTRODUCTIONDopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects....
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SourceType Open Access Repository
Aggregation Database
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Publisher
StartPage 50
SubjectTerms Adult
Aged
Aged, 80 and over
Biomarkers
Cognition Disorders - etiology
DDS
Depression
Disruptive, Impulse Control, and Conduct Disorders - diagnosis
Disruptive, Impulse Control, and Conduct Disorders - etiology
Dopamine Dysregulation Syndrome
Dyskinesias
Dyskinesias - diagnosis
Dyskinesias - etiology
Female
Hallucinations
Humans
ICD
Impulse control disorders
Logistic Models
Male
Middle Aged
Motor subtypes
Parkinson Disease - complications
Parkinson Disease - drug therapy
Parkinson Disease - psychology
Parkinson's disease
Psychiatric Status Rating Scales
Psychotic Disorders - diagnosis
Psychotic Disorders - etiology
Severity of Illness Index
Title Markers of impaired motor and cognitive volition in Parkinson's disease: Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias
URI https://dx.doi.org/10.1016/j.parkreldis.2017.11.338
https://www.ncbi.nlm.nih.gov/pubmed/29198499
https://www.proquest.com/docview/1972300420
https://pubmed.ncbi.nlm.nih.gov/PMC5803355
Volume 47
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