Objective: The goal of the Parkinson Associated Risk Syndrome (PARS) study is to explore the clinical and biomarker trajectory of individuals in the pre-motor phase of Parkinson disease (PD) who were sought out using olfactory testing and sequential DAT imaging.

Background: The PARS study was originally conceived to test whether a two-stage screening strategy consisting of olfactory assessment followed by DAT imaging could identify a cohort “at risk” for PD. PARS subjects with an olfactory deficit have been followed for 6 years with longitudinal imaging and clinical assessments.

Methods: Hyposmic subjects completed baseline, 2-yr, 4-yr and 6 yr clinical and 123I-ß-CIT/SPECT evaluations. Survival analysis was used to assess risk of conversion to motor PD and/or to a scan with DAT deficit (<65% age-expected lowest putamen) among subjects who did not have abnormal scans at baseline. Clinical conversion was assessed by study investigators blinded to DAT imaging and olfactory status. In addition, we compared the annualized rate of change in striatal DAT binding for individuals who converted clinically to the rate for non-converters.

Results: At baseline, participants were categorized based on DAT imaging: DAT deficit (n=21), DAT indeterminate (n=30) or no DAT deficit (n=134). During the 6-year follow-up period, 66.7% (n=14) of DAT deficit subjects, 20.0% (n=6) of DAT indeterminate subjects and 4.5% of no DAT deficit subjects were assigned a Parkinson diagnosis. For those subjects with >65% of age-expected putamen at baseline a reduction to <65% occurred in 19 subjects, 12/30 (40.0%) with indeterminate DAT at Baseline and 7/134 (5.2%) with no DAT deficit at Baseline. The annual percentage decline in striatal DAT binding in subjects who clinically converted was significantly greater than in subjects who did not convert (-5.1% v -1.2%, p < 0.0001).

Conclusions: Longitudinal follow-up of hyposmic subjects in the PARS cohort demonstrates a sequential pattern of progression characterized by imaging biomarker conversion followed by clinical conversion. These results have implications for understanding the prodromal phase of PD and for planning PD prevention trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-imaging-progression-in-the-pars-cohort-results-from-6-years-of-observation/