Objective: We report clinical and imaging phenoconversion data at 6 years follow-up for the PARS cohort.

Background: The PARS cohort consists of 203 hyposmic and 100 normosmic subjects without a diagnosis of PD at baseline.  Baseline DAT imaging indicates 11% of hyposmic subjects have DAT deficit (<65% of age expected putamen binding ratio) indicating they may be at increased risk for developing PD.

Methods: Subjects completed baseline, 2yr, 4yr, 6yr clinical and ¹²³I-ß-CIT/SPECT evaluations.  Clinical evaluations (UPDRS, cognitive testing, diagnosis assignment) were performed blind to imaging and olfactory data. Annualized changes from baseline in striatal binding ratio (SBR) were compared based on olfactory and DAT imaging status. Phenoconversion to clinical PD was defined by the clinical investigator’s best current diagnosis and/or by imaging change to lowest putamen DAT binding ≤65% age expected at 2yr, 4yr, 6yr visits.

Results: 203 hyposmics completed baseline assessments, 177 completed 2yr, 147 completed 4 yr, and 119 completed 6yr scans. Among hyposmics with a DAT deficit ≤65% at baseline 14/23 (61%) converted to clinical PD.   Among hyposmics with DAT 65%-80% at baseline 12/34 (35%) converted to DAT deficit ≤65%, and among hyposmics with DAT >80% at baseline 8/146 (5%) converted to DAT deficit ≤65%. Mean annualized percent change in SBR from baseline among those hyposmic subjects with an SBR ≤65% at any scan was approximately 5.6% (±4.4). Overall 27 hyposmic subjects were given a clinical diagnosis of parkinsonism by year 6.

Conclusions: Longitudinal follow-up of the PARS cohort demonstrates that about  60% of hyposmic DAT deficit ≤65% of age expected at baseline converted to clinical parkinsonism within 6 years.  Further hyposmic subjects with baseline DAT >65% show DAT imaging conversion to ≤65% of age expected during follow-up, suggesting an incident DAT deficit that may precede clinical symptoms.  The rate of DAT loss during this 6-year period among those with a DAT ≤65% was similar to the rate of DAT loss in early PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-imaging-and-phenoconversion-in-the-pars-prodromal-cohort/