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

• Published in: Parkinsonism & 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
• Language: English
• Published: England Elsevier Ltd 01.02.2018
• Subjects: 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; Dyskinesias; DDS; Motor subtypes; Parkinson's disease; Impulse control disorders; Hallucinations; Depression; ICD; Dopamine Dysregulation Syndrome
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2017.11.338

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.