Hinkle Jared T, Perepezko Kate, Gonzalez Lorenzo L, Mills Kelly A, Pontone Gregory M
Medical Scientist Training Program Johns Hopkins University School of Medicine Baltimore Maryland USA.
Department of Psychiatry Johns Hopkins University School of Medicine Baltimore Maryland USA.
Mov Disord Clin Pract. 2020 Dec 4;8(1):76-84. doi: 10.1002/mdc3.13117. eCollection 2021 Jan.
Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT).
To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT.
We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS).
The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose).
Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.
神经精神症状和情感症状在帕金森病（PD）前驱期和临床期很常见。一些证据表明，它们也可能预示多巴胺替代疗法（DRT）出现运动并发症（运动波动和异动症）的风险。
确定新发PD（即开始DRT之前）中存在的神经精神症状是否能预测DRT最终运动并发症的严重程度。
我们使用了帕金森病进展标志物倡议（PPMI）的临床、人口统计学、神经行为和神经影像学数据，这是一项多中心观察性PD研究。参与者在入组时未接受药物治疗，361人在PPMI随访期间开始接受DRT。我们使用Cox比例风险模型和多变量有序混合效应回归模型，以运动障碍学会修订的统一帕金森病评定量表（MDS-UPDRS）衡量，评估基线神经精神症状与运动并发症之间的关系。
随访期间（6.0±1.5年）异动症和运动波动的累积发生率分别为34.3%和59.9%。淡漠和高特质焦虑（前四分位数）使异动症发作风险以及异动症和运动波动对日常生活活动造成的不良影响风险增加了两倍多。运动波动和异动症的纵向严重程度可由基线特质焦虑和淡漠显著预测，但不能由抑郁预测。模型针对维度相关症状（如自主神经功能障碍）和潜在混杂变量（如DRT剂量）进行了调整。
新发PD中的淡漠和焦虑水平可能是DRT发生更早且更致残的运动并发症易感性的神经精神生物标志物。
