An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease

Abstract

Although the presence of an olfactory impairment in Parkinson's disease (PD) has been recognized for 25 years, its cause remains unclear. Here we suggest a contributing factor to this impairment, namely, that PD impairs active sniffing of odorants. We tested 10 men and 10 women with clinically typical PD, and 20 age- and gender-matched healthy controls, in four olfactory tasks: (i) the University of Pennsylvania smell identification test; (ii and iii) detection threshold tests for the odorants vanillin and propionic acid; and (iv) a two-alternative forced-choice detection paradigm during which sniff parameters (airflow peak rate, mean rate, volume, and duration) were recorded with a pneomatotachograph-coupled spirometer. An additional experiment tested the effect of intentionally increasing sniff vigor on olfactory performance in 20 additional patients. PD patients were significantly impaired in olfactory identification (P < 0.0001) and detection (P < 0.007). As predicted, PD patients were also significantly impaired at sniffing, demonstrating significantly reduced sniff airflow rate (P < 0.01) and volume (P < 0.002). Furthermore, a patient's ability to sniff predicted his or her performance on olfactory tasks, i.e., the more poorly patients sniffed, the worse their performance on olfaction tests (P < 0.009). Finally, increasing sniff vigor improved olfactory performance in those patients whose baseline performance had been poorest (P < 0.05). These findings implicate a sniffing impairment as a component of the olfactory impairment in PD and further depict sniffing as an important component of human olfaction.

Figure 1

Methods for recording airflow. A schematic drawing and image of the recording apparatus as used in refs. and (note the three additional interchangeable odorant sources at the table). Subjects were told that the tubes connected to the mask were the odorant supply (they were in fact the pressure transduction tubes). Subsequent questioning revealed that no subject was aware of the ongoing airflow recording. The data in the upper right quadrant is the actual mean first sniff of 20 patients and 20 controls (the person demonstrating the apparatus is not a patient).

Figure 2

Olfaction in patients and controls. Patients performed worse than controls in all olfactory tasks. (a) Relative to the controls, who performed within the range of published norms (16), patients' performance on the UPSIT was near anosmia (complete olfactory loss). The detection threshold scores achieved represent the following concentrations. (b) For vanillin, controls = 1.09 × 10⁻⁴ M in H₂O, patients = 1.13 × 10⁻³ M in H₂O. (c) For propionic acid, controls = 5.27 × 10⁻⁴ M in H₂O, patients = 3.8 × 10⁻³ M in H₂O. As previously shown (16), olfactory performance was not significantly correlated in patients with finger tapping, age, disease duration, cognitive state (Mini Mental State Examination), or stage of disease progression (Hoehn and Yahr scale).

Figure 3

Sniffing in patients and controls. Patients displayed significantly reduced sniff airflow (a) peak rate, (b) mean rate, (c) volume, and (d) overall bout volume. There was no difference between patients and controls in (e) sniff duration and (f) number of sniffs attempted in a bout before making a decision. Sniffing performance was not significantly correlated in patients with finger tapping, age, disease duration, cognitive state (Mini Mental State Examination), or stage of disease progression (Hoehn and Yahr scale).

Figure 4

Predictors of olfactory performance in PD. (a) Better sniffing predicted better olfactory performance in PD. (b) Motor performance as assessed by finger tapping did not significantly predict olfactory performance in PD. (c) Motor performance as assessed by a standard test (UPDRS part III) did not significantly predict olfactory performance in PD. (d) A subset of the UPDRS part III, representing only axial function, significantly predicted olfactory performance in PD (note that one subject had a significantly outlying UPDRS score and is therefore not depicted in the scattergram. Graph c remained insignificant, and d remained significant, with or without this subject).

Figure 5

Effects of increasing sniff volume on olfactory performance. (a) Increases in sniff volume from spontaneous sniffing (Pre) to sniffing after instructions (Post), in the 10 worst olfactory performing patients. (b) Improvement in olfactory performance between baseline (Pre) and after sniff volume increases (Post) in the same 10 worst olfactory performing patients. Increasing sniff volume led to a significant improvement in performance.