The World Smells Different in Parkinson’s Disease

Abstract Olfactory decline is a well-established aspect of Parkinson’s disease (PD) and is considered one of its earliest signs, often preceding motor symptoms by years to decades. However, because olfactory impairment is also common in healthy aging and other medical conditions, current olfactory tests that score performance (odor detection, discrimination, and identification) lack disease specificity. In contrast to performance scores, olfactory perceptual fingerprints are derived from odor ratings and sniffing behavior, and provide a stable measure of how the world smells to an individual. To test the hypothesis that olfactory perceptual fingerprints may provide a disease-specific marker, we obtained them in three cohorts: Individuals with PD (n=33), healthy age-matched controls (n=33), and critically, in participants with non-PD olfactory dysfunction (n=28). Consistent with previous results, a standard clinical olfactory test detected impairment in both PD and non-PD olfactory dysfunction, but failed to distinguish between these two groups. In contrast, olfactory perceptual fingerprints detected impairment, and distinguished PD from non-PD olfactory dysfunction at 88% accuracy (SVM classification, leave-one-out cross validation, 90% sensitivity, 85% specificity, P =3.2×10 -4 ), or 94% accuracy after matching age and sex (SVM classification, leave-one-out cross-validation, 100% sensitivity, 88% specificity, P =0.0047). The difference between PD related and unrelated olfactory decline was particularly evident in sniffing behavior: Whereas both healthy participants and non-PD olfactory decline groups decreased sniff duration in response to unpleasant odors (−12.5% and −11.36% respectively), individuals with PD paradoxically increased sniff duration (+1.69%; P=4.5×10 -5 ). Thus, PD was marked not by loss of olfactory performance, but by a distinct shift in olfactory perception. These findings imply that olfactory perceptual fingerprints provide for a disease-specific marker in PD.