Jennings Danna, Siderowf Andrew, Stern Matthew, Seibyl John, Eberly Shirley, Oakes David, Marek Kenneth
Institute for Neurodegenerative Disorders, New Haven, Connecticut.
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
JAMA Neurol. 2017 Aug 1;74(8):933-940. doi: 10.1001/jamaneurol.2017.0985.
Detecting individuals at risk for Parkinson disease (PD) during the prodromal phase could clarify disease mechanisms and allow for treatment earlier in the disease process to possibly slow or prevent the onset of motor PD.
To determine if the combination of smell identification testing followed by dopamine transporter (DAT) imaging can accurately and efficiently identify individuals from the general population at risk for conversion to a clinical diagnosis of PD.
DESIGN, SETTING, AND PARTICIPANTS: Participants were identified from the community by olfactory testing assessed longitudinally with DAT imaging 2 and 4 years after baseline and by annual clinical follow-up to determine whether they had clinical evidence to establish a PD diagnosis. Participants were contacted by mail and completed olfactory testing at home. Longitudinal follow-up of clinical measures and DAT imaging occurred at specialty centers. There were 203 hyposmic and 100 normosmic participants. A total of 185 hyposmic and 95 normosmic individuals had at least 1 follow-up visit, and 152 hyposmic participants (82.2%) were either observed for 4 years or converted to PD during follow-up.
Percentage of individuals with hyposmia and a DAT deficit that converted to PD and the change in PD clinical scale scores (Unified Parkinson's Disease Rating Scale) and DAT imaging during 4-year follow-up.
Of 280 total participants, 140 (50.0%) were male, and the mean (SD) age of the cohort was 63 (8.7) years. Among 21 participants with hyposmia and a DAT deficit (65% or less of age-expected lowest putamen binding ratio) at baseline, 14 (67%) converted to PD at 4 years compared with 2 of 22 participants (9%) with a DAT in an indeterminate range (greater than 65%-80%) and 3 of 109 participants (2.8%) with no DAT deficit (greater than 80%) at baseline. Individuals with a baseline DAT deficit experienced a 4-year decline in DAT binding of 20.23% (SD, 15.04%) compared with 3.68% (SD, 18.36%) and 5.45% (SD, 13.58%) for participants with an indeterminate and no DAT deficit, respectively (P = .002). The relative risk of conversion to a diagnosis of PD in hyposmic individuals with a DAT deficit was 17.47 (95% CI, 7.02-43.45) compared with individuals with either indeterminate or no DAT deficit.
The combination of hyposmia and DAT deficit was highly predictive of conversion to PD within 4 years of clinical follow-up. Individuals with hyposmia and a DAT deficit had a 5% reduction in DAT binding annually, similar to early PD. These results provide a framework for planning disease prevention studies in PD.
在帕金森病（PD）前驱期检测出有患病风险的个体，有助于阐明疾病机制，并能在疾病进程中更早地进行治疗，从而有可能延缓或预防运动性PD的发作。
确定嗅觉识别测试联合多巴胺转运体（DAT）成像能否准确、高效地从普通人群中识别出有转化为临床PD诊断风险的个体。
设计、背景和参与者：通过嗅觉测试从社区中招募参与者，在基线后的第2年和第4年进行DAT成像纵向评估，并通过年度临床随访来确定他们是否有临床证据可确诊为PD。通过邮件联系参与者，他们在家中完成嗅觉测试。临床指标和DAT成像的纵向随访在专科中心进行。有203名嗅觉减退者和100名嗅觉正常者。共有185名嗅觉减退者和95名嗅觉正常者至少进行了1次随访，152名嗅觉减退参与者（82.2%）在随访期间被观察了4年或转化为PD。
嗅觉减退且有DAT缺陷并转化为PD的个体百分比，以及在4年随访期间PD临床量表评分（统一帕金森病评定量表）和DAT成像的变化。
在280名总参与者中，140名（50.0%）为男性，队列的平均（标准差）年龄为63（8.7）岁。在基线时21名嗅觉减退且有DAT缺陷（壳核结合率低于年龄预期最低值的65%）的参与者中，14名（67%）在4年后转化为PD，相比之下，22名DAT处于不确定范围（大于65%-80%）的参与者中有2名（9%）转化，109名基线时无DAT缺陷（大于80%）的参与者中有3名（2.8%）转化。基线时有DAT缺陷的个体在4年中DAT结合下降了20.23%（标准差，15.04%），而DAT处于不确定范围和无DAT缺陷的参与者分别下降了3.68%（标准差，18.36%）和5.45%（标准差，13.58%）（P = 0.002）。与DAT处于不确定范围或无DAT缺陷的个体相比，嗅觉减退且有DAT缺陷的个体转化为PD诊断的相对风险为17.47（95%可信区间，7.02-43.45）。
嗅觉减退和DAT缺陷的联合表现对临床随访4年内转化为PD具有高度预测性。嗅觉减退且有DAT缺陷的个体每年DAT结合下降5%，与早期PD相似。这些结果为规划PD疾病预防研究提供了一个框架。
