Weintraub Daniel, Picillo Marina, Cho Hyunkeun Ryan, Caspell-Garcia Chelsea, Blauwendraat Cornelis, Brown Ethan G, Chahine Lana M, Coffey Christopher S, Dobkin Roseanne D, Foroud Tatiana, Galasko Doug, Kieburtz Karl, Marek Kenneth, Merchant Kalpana, Mollenhauer Brit, Poston Kathleen L, Simuni Tanya, Siderowf Andrew, Singleton Andrew, Seibyl John, Tanner Caroline M
Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA.
Assistant Professor in Neurology at the Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" University of Salerno Italy.
Mov Disord Clin Pract. 2023 Apr 25;10(6):943-955. doi: 10.1002/mdc3.13751. eCollection 2023 Jun.
Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).
We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD.
PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment.
Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values ( range 0.003-0.005) and higher LEDD over time ( range <0.001-0.01) were significantly associated with increased risk for CI.
Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.
Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023).
关于多巴胺系统对帕金森病（PD）认知障碍（CI）发展的影响，目前所知甚少。
我们使用来自一项多中心、国际性、前瞻性队列研究的数据，以探讨多巴胺系统相关生物标志物对PD患者CI的影响。
从疾病发作开始，对PD参与者进行为期7年的年度评估，并通过对以下四项指标应用临界值来确定CI：（1）蒙特利尔认知评估；（2）详细的神经心理测试组；（3）运动障碍协会统一帕金森病评定量表（MDS-UPDRS）认知评分；（4）研究现场调查员对CI（轻度认知障碍或痴呆）的诊断。通过连续的碘-123 碘氟烷多巴胺转运体（DAT）成像、基因分型以及每次评估时记录的左旋多巴等效日剂量（LEDD）来评估多巴胺系统。经过多重比较调整的多变量纵向分析确定了多巴胺系统相关生物标志物与CI（包括持续性损伤）之间的关联。
与CI相关的人口统计学和临床变量包括年龄较大、男性、教育程度较低、非白人种族、抑郁和焦虑评分较高以及MDS-UPDRS运动评分较高。对于多巴胺系统，较低的基线平均纹状体多巴胺转运体值（范围为0.003 - 0.005）以及随时间推移较高的LEDD（范围为<0.001 - 0.01）与CI风险增加显著相关。
我们的结果提供了初步证据，表明多巴胺系统的改变可预测帕金森病中临床相关认知障碍的发展。如果得到重复验证并确定具有因果关系，这些结果表明多巴胺系统在整个疾病过程中对认知健康状况起着重要作用。
帕金森病进展标志物计划已在ClinicalTrials.gov注册（NCT01141023）。
