Fig. 1: NSD-ISS Applied to BioFIND.

A Selection of BioFIND participants with evidence of α-synuclein as biological anchor through CSF α-synuclein seed amplification assay (αSyn-SAA). These 104 S+ participants were stageable by NSD-ISS criteria. A single bar plot shows the number and percentage of S+ participants within each clinical stage. Again, no dopamine imaging is available within BioFIND, so these participants are minimally stage 2 A and likely stage 2B, but we did not make this distinction. B Duration of disease, defined as time since diagnosis, for all participants, within each clinical stage. Each marker is a single participant. Black bars represent median, and colored blocks indicate interquartile range (stage 2: 5.4 [2.3]; stage 3: 5.8 [4.9]; stage 4: 6.5 [4.1]; stage 5: 10.8 [4.5]; median [IQR], non-parametric Kruskal-Wallis H-statistic 87.5, p = 0.44). C MDS-UPDRS Part III score when off of motor medications (OFF) is plotted versus MDS-UPDRS Part II scores for each S+ participant – each point represents single participant. NSD-ISS stages are represented by color with key provided in legend. Note the variability of MDS-UPDRS Part III OFF scores within each stage, and overlap across stages. Dotted lines indicate the 25th, 50th (median), and 75th percentiles of UPDRS Part III OFF scores. D Bar plots indicating distributions of NSD-ISS stages within each Hoehn & Yahr (HY) stage within BioFIND (percentages indicate fraction of each NSD-ISS stage within each HY stage). E Fraction of tremor-dominant (TD) and postural instability & gait difficulty (PIGD) motor phenotypes within each NSD-ISS stage within BioFIND. F Plot of Montreal Cognitive Assessment (MoCA) score versus MDS-UPDRS Part I Question 1.1 score (Q1.1) for each BioFIND participant, with stages indicated by color. Dotted line indicates MoCA score = 25, which is the typical delineation of mild cognitive impairment and is the demarcation of cognitive progression in the NDS-ISS. Points are ‘jittered’ from the integral abscissa for visibility.