Table 1.

Staging anchors for application of the NSD-ISS

	Biologic anchors			Anchors of clinical signs or symptoms (stages 2A and 2B) and functional impairment (stages 3–6)1,2
Stage	S	D a	G	Domain	Anchor(s)
Stage 0	-	-	SNCA b	—	—
Stage 1A	+	-	±	(1) Cognitive (2) Motor (3) Other non-motor	(1) MDS-UPDRS item 1.1=0; and (2a) Does not have subthreshold parkinsonism c; and (2b) is not on PD medicationd; and (3a) Does not have RBD; and (3b) is not hyposmic d
Stage IB	+	+	±
Stage 2A	+	-	±	(1) Cognitive (2) Motor (3) Other non-motor	(1) Item 1.1 = 1 AND MoCA ≥ 25; or (2a) Has subthreshold parkinsonism c; or (2b) is on PD medicationd; or (3a) Has RBD; or (3b) is hyposmice
Stage 2B	+	+	±
Stage 3	+	+	±	(1) Cognitive (2) Motor	(1a) Item 1.1 = 1 AND MoCA ≤ 24; or (1b) Item 1.1 = 2 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 3–13 AND either subthreshold parkinsonism c or PD medicationd
Stage 4	+	+	±	(1) Cognitive (2) Motor (3) Other non-motor	(1a) Item 1.1 = 2 and MoCA ≤ 24; or (1b) item 1.1 = 3 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 14–26; or (3) MDS-UPDRS-I (excluding item 1.1) = 13–24f
Stage 5	+	+	±	(1) Cognitive (2) Motor (3) Other non-motor	(1a) Item 1.1 = 3 AND MoCA ≤ 24; or (1b) item 1.1 = 4 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 27–39; or (3) MDS-UPDRS-I (excluding item 1.1) = 25–36
Stage 6	+	+	±	(1) Cognitive (2) Motor (3) Other non-motor	(1) Item 1.1 = 4 AND MoCA ≤ 24; or (2) MDS-UPDRS-II ≥ 40; or (3) MDS-UPDRS-I (excluding item 1.1) ≥ 37