Objective: A major goal of the Parkinson Progression Marker Initiative (PPMI) is to identify clinical and biomarker defined disease subsets that may demonstrate differing disease severity at baseline and progression.  We examined olfactory function in the PPMI-LRRK2 PD participants cohort to determine whether it might be used to establish meaningful sub-groups within this cohort.

Background: The Parkinson Progression Marker Initiative is a comprehensive, longitudinal, observational, multi-center natural history study to assess clinical and biomarkers of disease progression.  Participants with the G2019S LRRK2 mutation were enrolled as part of the genetic PPMI cohort.  Recent data suggests that LRRK2 PD may have mixed synuclein and tau pathology.
 

Method: All PPMI participants were evaluated with the University of Pennsylvania Smell Identification Test (UPSIT), a 40-item scratch and sniff test that has been widely used to assess PD and other neurologic disorders.  Robust control UPSIT data from PPMI and the PARS was used to determine a percentile score corrected for  age and sex for each study participant[TC1] . Clinical and biomarker analysis of the PPMI LRRK2 participants was divided into those with UPSIT percentile <5 (severe hyposmia), 6-15 (moderate hyposmia), >15 (normosmic).

Results: UPSIT percentile at baseline in PPMI LRRK2-PD with G2019S mutation showed <5 (n=46), 6-15 (n=35, >15 (n=55).  Age was 60.2 (9.3), 63.1 (9.3), 63.1 (9.3) in the <5, 6-15, >15 groups, with p<.05 between <5 and>15.  Total MDS-UPDRS  was 45.6 (20.4), 41.3 (19.0), 31.8 (14.7) in the <5, 6-15, >15 groups, with p<.05 between <5 and>15. DAT contralateral putamen SBR was 0.60 (0.29), 0.63 (0.20), 0.80 (0.45) in the <5, 6-15, >15 groups, with p<.01 between <5 and>15.  The trend for cognitive function was similarly more severe in the <5 compared to the >15 groups.

Conclusion: PPMI LRRK2-PD participants show increased clinical and biomarker severity at baseline in those participants with severe hyposmia by UPSIT. These data suggest that olfactory function may identify LRRK2 subsets that may warrant consideration in design of LRRK2 clinical trials and may reflect mixed LRRK2 synuclein and tau pathology.   

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MDS Abstracts - https://www.mdsabstracts.org/abstract/defining-lrrk2-pd-subsets-based-on-olfactory-function-in-the-ppmi/