Imaging prodromal Parkinson disease: the Parkinson Associated Risk Syndrome Study

Abstract

Objectives: The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD).

Methods: In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [(123)I]β-CIT striatal binding ratio in hyposmic and normosmic subjects.

Results: Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%.

Conclusion: Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD.

Figure 1. PARS Study flowchart

Flowchart illustrating the overall design of the PARS Study. PARS = Parkinson Associated Risk Syndrome; UPSIT = University of Pennsylvania Smell Identification Test.

Figure 2. Factors influencing the risk of DAT deficit

Factors influencing the risk of DAT deficit (≤65% age-expected DAT binding in lowest putamen); family hx of PD = one or more first-degree relatives with PD; constipation ≤1 bowel movement/d; subtle motor sx = endorsing ≥2 symptoms on the PD Symptom Rating Scale; RBD = endorsing any symptom more than once per month. DAT = dopamine transporter; PD = Parkinson disease; RBD = REM behavior disorder.