帕金森病中的嗅觉障碍与可能的快速眼动睡眠行为障碍：与单次打击和双重打击假说的临床相关性
Olfactory impairment and probable REM sleep behavior disorder in Parkinson's disease: clinical relevance to the single- and dual-hit hypotheses.
文献信息
| PMID | 42840315 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Chia-Yen Lin |
| 作者单位 | Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. |
| 期刊 | Frontiers in aging neuroscience |
| SCI 分区 | Q1 |
| IF | 5.6 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 快速眼动（REM）睡眠行为障碍（RBD）和嗅觉障碍是帕金森病（PD）常见的前驱期特征，但二者共存的意义仍不确定。双重打击假说提出同时存在嗅觉和肠道受累，而修订后的单次打击框架则提出以脑为首或以身为主的路径。我们检验了由可能的RBD（pRBD）/嗅觉缺失定义的亚组是否表现出不同的临床特征。
方法： 在这项横断面研究中，201名PD患者接受了嗅觉、认知、运动、非运动和生活质量评估。嗅觉缺失定义为宾夕法尼亚大学嗅觉识别测试评分<19，pRBD定义为RBD筛查问卷评分≥6并辅以参与者和知情者访谈。多变量模型评估了嗅觉缺失和pRBD的主效应及交互效应。
结果： 在201名参与者中，95名（47.3%）为pRBD阳性（pRBD+），135名（67.2%）有嗅觉缺失，68名（33.8%）两者兼有。嗅觉缺失患病率在pRBD+组和pRBD阴性（pRBD-）组之间没有差异（71.6% vs. 63.2%；p = 0.208）。在调整年龄、性别和病程后，pR+A+和pR+A-（由可能的RBD状态[pR+/pR-]和嗅觉缺失状态[A+/A-]定义的亚组）在任何评估结局上均无差异。嗅觉缺失与pRBD的交互作用对MDS-UPDRS第三部分为负（β = -8.3，95% CI -15.2至-1.4；p = 0.019）。在pRBD-亚组内，pR-A+参与者的MoCA评分低于pR-A-参与者（β = -2.6；95% CI -4.1至-1.0；p = 0.001），且嗅觉缺失与pRBD的交互作用对MoCA为正（β = 2.3，95% CI 0.0至4.5；p = 0.049）。嗅觉缺失与pRBD-参与者的认知障碍相关（OR 2.53，95% CI 1.00-6.37；p = 0.049），但在pRBD+参与者中不相关（OR 1.65，95% CI 0.60-4.50；p = 0.331）。
结论： 在pRBD+参与者中，嗅觉缺失与更严重的运动严重程度无关；而在pRBD-参与者中，它反而与认知障碍相关。同时评估嗅觉和pRBD可能改善临床表型划分，但需要纵向验证。
英文摘要
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) and olfactory impairment are common prodromal features of Parkinson's disease (PD), but the implications of their coexistence remain uncertain. The dual-hit hypothesis proposes concomitant olfactory and enteric involvement, whereas the revised single-hit framework proposes predominantly brain-first or body-first routes. We examined whether probable RBD (pRBD)/anosmia-defined subgroups exhibit distinct clinical profiles.
METHODS: In this cross-sectional study, 201 individuals with PD underwent olfactory, cognitive, motor, non-motor, and quality-of-life assessments. Anosmia was defined as a University of Pennsylvania Smell Identification Test score <19 and pRBD as an RBD Screening Questionnaire score ≥6 supplemented by participant and informant interviews. Multivariable models evaluated the main and interactive effects of anosmia and pRBD.
RESULTS: Of 201 participants, 95 (47.3%) were pRBD-positive (pRBD+), 135 (67.2%) had anosmia, and 68 (33.8%) had both. Anosmia prevalence did not differ between the pRBD+ and pRBD-negative (pRBD-) groups (71.6% vs. 63.2%; p = 0.208). After adjustment for age, sex, and disease duration, pR+A+ and pR+A- (subgroups defined by probable RBD status [pR+/pR-] and anosmia status [A+/A-]) did not differ in any assessed outcome. The anosmia-by-pRBD interaction was negative for MDS-UPDRS part III (β = -8.3, 95% CI -15.2 to -1.4; p = 0.019). Within the pRBD- subgroup, pR-A+ participants had lower MoCA scores than pR-A- participants (β = -2.6; 95% CI -4.1 to -1.0; p = 0.001), and the anosmia-by-pRBD interaction was positive for MoCA (β = 2.3, 95% CI 0.0 to 4.5; p = 0.049). Anosmia was associated with cognitive impairment in pRBD- participants (OR 2.53, 95% CI 1.00-6.37; p = 0.049), but not in pRBD+ participants (OR 1.65, 95% CI 0.60-4.50; p = 0.331).
CONCLUSION: In pRBD+ participants, anosmia was not associated with greater motor severity; in pRBD- participants, it was instead linked to cognitive impairment. Concurrent assessment of olfaction and pRBD may improve clinical phenotyping, but longitudinal validation is required.