Data_Sheet_1_Olfactory Deficits in the Freezing of Gait Phenotype of Parkinson's Disease.PDF

Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures.
Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait.
Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined.
Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized.
Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.

研究背景：帕金森病（Parkinson's disease, PD）患者的嗅觉功能障碍常早于运动症状发作，可通过宾夕法尼亚大学嗅觉识别试验（University of Pennsylvania Smell Identification Test, UPSIT）进行检测。基于布拉凯假说（Braak hypothesis），嗅球是该病病理起始并扩散至脑深部结构的两个位点之一。
研究目标：本研究旨在评估UPSIT中特定的气味识别模式，能否区分伴与不伴步态冻结（freezing of gait）的帕金森病患者。
研究方法：共纳入124例连续入组受试者（33例对照者、31例非步态冻结者、60例步态冻结者），所有受试者均接受UPSIT检测。采用卡方检验（chi-square test），依据步态冻结者与非步态冻结者的气味正确识别差异能力，对UPSIT中的每种气味进行排序。通过预测统计分析与混淆矩阵（confusion matrices），确定最优气味组合及临界评分。
研究结果：基于年龄与性别校正的标准化参考值，步态冻结者的嗅觉减退程度更为严重。与非步态冻结者相比，步态冻结者对9种气味（泡泡糖、巧克力、烟雾、冬青油、油漆稀释剂、橙子、草莓、青草、花生）的正确识别率显著更低。在3种气味（泡泡糖、巧克力、烟雾）中，正确识别数≤2种时，对步态冻结者的分类灵敏度为77%，特异度为61%。该3种气味的识别得分与病程、运动分项统一帕金森病评定量表（Unified Parkinson's Disease Rating Scale, UPDRS）得分、总UPDRS得分、蒙特利尔认知评估（Montreal Cognitive Assessment, MoCA）得分及测试时年龄均无相关性。按性别分别分组分析时，预测统计结果相似。
研究结论：基于3种气味的识别得分可有效区分步态冻结者与非步态冻结者，其灵敏度与特异度与短版气味识别帕金森病筛查量表相当。