Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome Study

Abstract

To test the association between impaired olfaction and other prodromal features of PD in the Parkinson At-Risk Syndrome Study. The onset of olfactory dysfunction in PD typically precedes motor features, suggesting that olfactory testing could be used as a screening test. A combined strategy that uses other prodromal nonmotor features, along with olfactory testing, may be more efficient than hyposmia alone for detecting the risk of PD. Individuals with no neurological diagnosis completed a mail survey, including the 40-item University of Pennsylvania Smell Identification Test, and questions on prodromal features of PD. The frequency of reported nonmotor features was compared across individuals with and without hyposmia. A total of 4,999 subjects completed and returned the survey and smell test. Of these, 669 were at or below the 15th percentile based on age and gender, indicating hyposmia. Hyposmics were significantly more likely to endorse nonmotor features, including anxiety and depression, constipation, and rapid eye movement sleep behavior disorder symptoms, and to report changes in motor function. Twenty-six percent of subjects with combinations of four or more nonmotor features were hyposmic, compared to 12% for those reporting three or fewer nonmotor features (P < 0.0001). Hyposmia is associated with other nonmotor features of PD in undiagnosed individuals. Further assessment of hyposmic subjects using more specific markers for degeneration, such as dopamine transporter imaging, will evaluate whether combining hyposmia and other nonmotor features is useful in assessing the risk of future neurodegeneration.

FIG. 1.

Flow diagram of ascertainment of study cohort. Reasons for ineligibility are given in the text.

FIG. 2.

Proportion of individuals with hyposmia in subjects with combinations of prodromal features. Prodromal features included the following: (1) having any RBD symptom at least once a month; (2) endorsing two or more items on the PD symptom self-report questionnaire; (3) having a CES-D score of greater than 15; (4) having a STAI-A or -B score of >39; or (5) having bowel movement frequency of <1 per day. Individuals with higher numbers of prodromal features, particularly four or five, are more likely to be hyposmic (P <0.0001).