Olfactory Impairment Can Identify Patients at Risk for Parkinson Disease


Olfactory impairment is indicative of rapid eye movement sleep behavior disorder, a prodromal symptom of Parkinson disease.

Laiquan Zou, PhD, associate professor, school of public health, Southern Medical University

Laiquan Zou, PhD

Data from a recent study suggest that olfactory impairment can be used as a sensitive and stable diagnostic biomarker of rapid eye movement sleep behavior disorder (RBD), a prodromal symptom of Parkinson disease (PD), to identify patients at risk for PD. 

Significant deficits were found in patients with RBD in measures such as odor identification (standardized mean difference [SMD or g], –1.80 [95% CI, –2.17 to –1.43]; Z = 9.53; P <.001), threshold (g = –1.29 [95% CI, –1.67 to –0.91]; Z = 6.72; P <.001), discrimination (g = –1.08 [95% CI, –1.28 to –0.87]; Z = 10.38; P <.001) and overall olfactory function (g = –1.67 [95% CI, –1.94 to –1.35]; Z = 10.93; P <.001). These impairments were not moderated by age, sex, disease duration, and education and were similar in patients with PD with or without RBD.

Senior author Laiquan Zou, PhD, associate professor, school of public health, Southern Medical University, and colleagues wrote that “we conducted a systematic review and comprehensive meta-analysis of the existing studies to investigate the significance of olfactory function in the diagnosis and prognosis (the risk of conversion to PD) of patients with RBD, and to assess moderating factors affecting olfactory performance.”

Zou and colleagues reviewed data from 3342 patients from 32 studies in this systematic review. Of all patients, 1366 had RBD, 555 had PD, 38 had both PD and RBD, and 1283 were healthy controls.

READ MORE: Community-Based Study Confirms REM Sleep Behavior Disorder Risk Factors

Odor identification scores were analyzed from 901 patients with RBD and 1033 controls, with patients with RBD performing significantly worse. Odor threshold was compared between 312 patients with RBD that performed significantly worse than the 271 controls. Similarly, the 265 patients with RBD performed significantly worse on odor discrimination than the 213 controls, and the 514 patients with RBD performed significantly worse on overall olfactory function than the 326 controls.

Zou and colleagues also analyzed studies investigating olfactory function between patients with RBD and patients with both RBD and PD. They found that the SMD was −0.36 [95% CI, −0.82 to 0.10]; Z = 1.55; P = .121), indicative of similar odor identification scores. 

The authors also found that patients with RBD had similar odor identification scores to patients with PD without RBD, with an SMD of (Z =1.77; P = .076 [95%CI, −0.83 to 0.04]). Sensitivity analyses confirmed all findings, and the authors also confirmed that performance was similar between different studies’ assessments of olfactory function.

Zou and colleagues also performed a meta-regression of heterogeneity found between studies and found a significant association between overall olfactory function scores and the Unified Parkinson's Disease Rating Scale part 3 (UPDRS-3) scores (P = .032), but not between UPDRS-3 and odor identification scores (P = .410), threshold (P = .516) or discrimination scores (P = .889). No demographic variables, such as age, sex, education length, or disease duration, had any significant associations with any measures of olfactory function.

“To our knowledge, this is the first systematic review and meta-analysis comparing olfactory functions among patients with RBD, patients with PD and HCs. We qualitatively and quantitatively synthesized data on different olfactory functions in patients with RBD and HCs; and we compared the odor identification impairment characteristics between patients with RBD and patients with PD. Our results confirmed research findings from the extant literature that patients with RBD suffered from significant olfactory impairment than healthy controls. In addition, we identified potential moderating factors affecting the psychophysical olfactory performance in patients with RBD using an exploratory meta-regression analysis,” Zou and colleagues concluded.

Lyu Z, Zheng S, Zhang X, et al. Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis. J. Neurol Neurosurg Psychiatry. Published online January 12, 2021. doi: 10.1136/jnnp-2020-325361
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