METHODS: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.
RESULTS: LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001).
CONCLUSIONS: This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.
方法:我们对PPMI队列进行了纵向分析,包括未服用药物的PD患者,他们逐渐暴露于多巴胺替代疗法(DRTs),以测试ADM暴露对LID发育的影响。
结果:LID患病率(根据MDSUPDRS评分4.1≥1)为16%(42/251);这些患者更可能是女性(p=0.01),具有较高的运动(p<0.001)和抑郁评分(p=0.01)和较低的putaminalDAT结合率(p=0.01)。LID与L-DOPA的暴露时间(2.2±1.07vs2.6±0.9,p=0.02)和ADM的暴露时间相关,特别是SNRI(4.8%对21.4%,p<0.001)。后者在校正了显著的协变量后仍然存在(例如,疾病持续时间,认知状态,运动障碍,抑郁症,多巴胺能神经支配)。在现实世界TriNetX存储库的匹配数据上观察到暴露于SNRI的PD患者中LID患病率的相似差异(22%vs13%,p<0.001)。
结论:本研究支持SNRI对早期PD患者LID引发的影响。有必要进行独立的前瞻性队列研究以进一步验证这种关联。