English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background:  Levodopa ( L -Dopa), representing the therapeutic gold standard for the treatment of Parkinson disease (PD), is associated with side effects like  L -Dopa induced dyskinesia (LID). Although several non-genetic and genetic factors have been investigated for association with LID risk, contrasting results were reported and its genetic basis remain largely unexplored.    Methods:  In an Italian PD cohort (N = 460), we first performed stepwise multivariable Cox Proportional Hazard regressions modeling LID risk as a function of gender, PD familiarity, clinical subtype, weight, age-at-onset (AAO) and years-of-disease (YOD),  L -Dopa dosage, severity scores, and scales assessing motor (UPDRS-III), cognitive (MoCA), and non-motor symptoms (NMS). Then we enriched the resulting model testing two variants—rs356219 and D4S3481—increasing the expression of the  SNCA  gene, previously suggested as a potential mechanism of LID onset. To account for more complex (non-linear) relations of these variables with LID risk, we built a survival random forest (SRF) algorithm including all the covariates mentioned above.    Results:  Among tested variables (N = 460 case-complete, 211 LID events; total follow-up 31,361 person-months, median 61 months), disease duration showed significant association ( p  < 0.005), with 6 (3–8)% decrease of LID risk per additional YOD. Other nominally significant associations were observed for gender—with women showing a 39 (5–82)% higher risk of LID—and AAO, with 2 (0.3–3)% decrease of risk for each year increase of PD onset. The SRF algorithm confirmed YOD as the most prominent feature influencing LID risk, with a variable importance of about 8% in the model. In genetic models, no statistically significant effects on incident LID risk was observed.    Conclusions:  This evidence supports a protective effect of late PD onset and gender (men) against LID risk and suggests a new independent protective factor, YOD. Moreover, it underlines the importance of personalized therapeutic protocols for PD patients in the future.

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