Epidemiology of Levodopa-Induced Dyskinesia

Analysis of Genetic and Non-genetic Predictors of Levodopa Induced Dyskinesia in Parkinson’s Disease

“…First, a multivariable analysis of non-genetic exposures previously implicated in LID onset showed a significant association with years of disease (YOD), which in our study conferred a protective effect. This is in contrast with previous studies reporting that patients with longer disease duration—which is only partly dependent on age at onset (AAO)—are more likely to develop LID ( Ahlskog and Muenter, 2001 ; Cilia et al, 2014 ; Coelho and Ferreira, 2014 ; Tran et al, 2018 ; Zhou et al, 2019 ). This discrepancy may be explained by the multivariable setting of our exploratory analysis, where also AAO showed a significant association with incident LID risk, in the expected direction (see below for further discussion).…”

“…PD stage has also been associated with LID risk, with patients in the early stage of the disease—with Hoehn and Yahr (HY) score of 1—showing a larger median time to LID from the beginning of L -Dopa treatment, compared to patients in a later HY stage ( Kostic et al, 2002 ). Likewise, dyskinesia has been reported to be less frequent and less severe in late-stage PD patients (see Coelho and Ferreira, 2012 ( Coelho and Ferreira, 2014 )). A recent analysis of Chinese PD patients revealed a positive association of prevalent LID risk with high HY scores and low Unified Parkinson’s disease Rating Scale part III (UPDRS-III) under active L -Dopa treatment, which suggested progression of the disease and severity of motor symptoms as risk factors, in addition to early AAO, long disease duration, gender (women being more affected), and high L -Dopa equivalent dose ( Zhou et al, 2019 ).…”

“…Dyskinesia is characterized by involuntary dystonic and/or choreic movements of the trunk, limbs, and face ( Finlay et al, 2014 ). One of the main risk factors predisposing to the onset of dyskinesia is Levodopa ( L -Dopa) dosage, which currently represents the therapeutic gold standard for Parkinson’s disease (PD) ( Coelho and Ferreira, 2014 ), which led to define a specific subtype of motor complications called L -Dopa Induced Dyskinesia (LID). Different risk factors have been associated with the onset of LID in PD patients, both modifiable and non-modifiable ( Prashanth et al, 2011 ).…”

“…Women generally show a greater incidence of dyskinesia than men ( Zappia et al, 2005 ; Warren et al, 2013 ) and tend to develop dyskinesia earlier in relation to time of L -Dopa administration ( Hassin-Baer et al, 2011 ). This may be due to a higher bio-availability of L -Dopa in women, which may be in turn be due to their usually lower body weight ( Coelho and Ferreira, 2014 ). However, a higher LID risk for women has not been confirmed in other studies ( Coelho and Ferreira, 2014 ; Campêlo and Silva, 2017 ).…”

“…This may be due to a higher bio-availability of L -Dopa in women, which may be in turn be due to their usually lower body weight ( Coelho and Ferreira, 2014 ). However, a higher LID risk for women has not been confirmed in other studies ( Coelho and Ferreira, 2014 ; Campêlo and Silva, 2017 ). Similarly, early PD onset was associated with an increased risk of LID: a 5-years follow-up study of PD patients showed a prevalence of LID up to 50% at age 40–59, and of 16% after 70 years ( Kumar et al, 2005 ), while another study found that the rates of dyskinesia in PD patients after 5 years of L -Dopa treatment were 70, 42, 33, and 24% for onsets at 40–49, 50–59, 60–69, and 70–79 years, respectively ( Ku and Glass, 2010 ).…”