Olfactory Testing in Parkinson's Disease & REM Behavior Disorder: A Machine Learning Approach.
Lo C., Arora S., Ben-Shlomo Y., Barber TR., Lawton M., Klein JC., Kanavou S., Janzen A., Sittig E., Oertel WH., Grosset D., Hu MT.
OBJECTIVE: We sought to identify an abbreviated test of impaired olfaction, amenable for use in busy clinical environments in prodromal (isolated REM sleep Behavior Disorder (iRBD)) and manifest Parkinson's disease (PD). METHODS: 890 PD and 313 control participants in the Discovery cohort study underwent Sniffin' stick odour identification assessment. Random forests were initially trained to distinguish individuals with poor (functional anosmia/hyposmia) and good (normosmia/super-smeller) smell ability using all 16 Sniffin' sticks. Models were retrained using the top 3 sticks ranked by order of predictor importance. One randomly selected 3-stick model was tested in a second independent PD dataset (n=452) and in two iRBD datasets (Discovery n=241; Marburg n=37) before being compared to previously described abbreviated Sniffin' stick combinations. RESULTS: In differentiating poor from good smell ability, the overall area under the curve (AUC) value associated with the top 3 sticks (Anise/Licorice/Banana) was 0.95 in the development dataset (sensitivity:90%, specificity:92%, positive predictive value:92%, negative predictive value:90%). Internal and external validation confirmed AUCs≥0.90. The combination of 3-stick model determined poor smell and an RBD screening questionnaire score of ≥5, separated iRBD from controls with a sensitivity, specificity, PPV and NPV of 65%, 100%, 100% and 30%. CONCLUSIONS: Our 3-Sniffin'-stick model holds potential utility as a brief screening test in the stratification of individuals with PD and iRBD according to olfactory dysfunction. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a 3-Sniffin'-stick model distinguishes individuals with poor and good smell ability and can be used to screen for individuals with iRBD.