20240722_184306

(Holden, 2018 #1123)

MDS-UPDRS scores increased in a linear fashion over 5 years in patients with de novo PD. MDSUPDRS total scores increased an estimated 4.7 points per year, Part I scores increased 0.99 points per year, and Part III scores increased 2.4 points per year.

	Mean ± SD
	Baseline, N = 362	Month 12, N = 318	Month 24, N = 312	Month 36, N = 317	Month 48, N = 240	Month 60, N = 107
Age, y	61.3 ± 9.8
Sex: Women, %	33.7
Treatment with dopaminergic medications, %	0.0	57.9	83.3	90.9	95.4	90.7
MDS-UPDRS score
Total	31.75 ± 12.99	38.33 ± 15.96	42.34 ± 17.31	45.78 ± 18.89	52.00 ± 22.43	54.89 ± 23.36
Part I	5.38 ± 3.97	6.74 ± 4.60	7.30 ± 4.84	8.06 ± 5.34	9.38 ± 6.02	9.84 ± 6.31
Part II	5.67 ± 4.13	7.27 ± 4.93	7.84 ± 5.25	8.57 ± 5.42	10.04 ± 6.64	10.73 ± 6.92
Part III	20.72 ± 8.85	24.11 ± 10.27	26.70 ± 11.26	28.37 ± 12.06	31.38 ± 12.84	32.54 ± 14.65
Part IV	NA	0.36 ± 1.20	0.60 ± 1.61	0.87 ± 1.85	1.34 ± 2.30	1.96 ± 2.51

Abbreviations: SD, standard deviation; MDS-UPDRS: Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale; NA, not applicable.

TABLE 2 Sample Size Estimations for the Detection of Disease Modification in a Hypothetical 1-Year Placebo-controlled Clinical Trial

Symptomatic Change in Treated Group	Mean Change in MDS-UPDRS Part III in Treated Group at 1 Year (Treatment Effect, % Attenuation)*	Total Sample Size [Per Group]
Slowing of progression	+4 (-2.35, 37%) +2 (-4.35, 69%)	480 [240] 142 [71]
Halting of progression	0 (-6.35, 100%)	68 [34]
Reversal of progression	-2 (-8.35, 131%) -4 (-10.35, 163%)	40 [20] 28 [14]

Abbreviations: MDS-UPDRS: Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale.
*Calculations were based on assumptions of 90% power; a mean ± standard deviation progression of 6.35 ± 6.66 points on MDS-UPDRS Part III for the untreated (control) group, as observed in Parkinson’s Progression Markers Initiative (PPMI) participants who were not taking dopaminergic medication at 1 year; and a standard deviation of 9.00 points on MDS-UPDRS Part III for the treated group, as observed in PPMI participants who were taking dopaminergic medication at 1 year. Sample size was allocated equally to the treatment and control groups and assumed that data from all participants were valid and usable.

Milestone-based approach

	Baseline clinical	Baseline clinical	Milestone 도시
A Milestone-based approach vs disease progression	M. Brumm, A. Siderowf, T. Simuni, C. Caspell-Garcia, L. Chahine, T. Foroud, V. Arnedo, A. Reimer, C. Tanner, K. Poston, D. Weintraub, S. Hutten, K. Kieburtz, K. Marek, C. Coffey. A Milestone-based approach to monitoring disease progression in Parkinson's disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a-milestone-based-approach-to-monitoring-disease-progression-in-parkinsons-disease/. Accessed May 15, 2023.		AD/PD 2023 Raphael T.Gerraty's poster RNA

Takeda UPDRS analysis

• Goals
  • approaches to identify items or factors within the UPDRS that are most sensitive to disease progression, or more broadly, to discuss endpoints that may be useful for internal decision-making.
• Topics
  • Analytic approach to identify factors that show the highest rate of progression (using UPDRS and/or other variables) and factors that demonstrate close correlation with rate of DaT scan progression.
  • intercurrent addition of dopaminergic therapy
  • time to event / progression milestone endpoints
• Resources
  • LINK is here

MoCA (Montreal Cognitive Assessment)

• 7 subscores: visuospatial/executive (5 points, ie this is more focused on rather than memory!); naming (3 points); memory (5 points for delayed recall); attention (6 points); language (3 points); abstraction (2 points); and orientation (6 points). One point is added if the subject has 12 years of education.
• MoCA declines only about 0.5 points over 5 years in PD (PPMI 2019 annual meeting)
• A score of 26 or over is considered to be normal. In a study, people without cognitive impairment scored an average of 27.4;
• cf: PR001A of Prevail’s NCT04127578 recuits MOCA<14
• https://www.mocatest.org/faq/ The cut-off score of 18 is usually considered to separate MCI from AD .
• https://www.mocatest.org/faq/.

	Range	Average
Full score		30
Normal	26-30	27.4
MCI	18-25	22
Mild AD	11-21	16
Moderate AD	10-17
Severe AD	<10

• MCID, minimal clinically important difference;

(Investigators, 2021 #1753) suppl3, eTable 1.2nd-1st: for MoCA is from Wu et al. Occup Ther Int. 2019 Apr 14;2019:2517658	1.2
(Wu, 2019 #2802)	The anchor-based MCID estimated was 1.22, which was calculated as the mean score of 23 participants reaching a change of 10% to 15% on the SIS-perceived recovery score. The distribution-based MCID, according to a 0.5 SD of the baseline, was 2.15

• conversion between MoCA and MMSE
  • (Lawton, 2016 #1547) 아래 Steenoven 방법과 저자 (Lawton) 방법 둘다 좋음.

TABLE 1. Conversion from MoCA to MMSE using the equipercentile method with log-linear smoothing using our datasets and compared to that from van Steenoven and colleagues

MoCA Total Adjusted	Equivalent MMSE Total (From the van Steenoven Article)	Equivalent MMSE Total (Internal Data Conversion)
	6	1
	9	2
	11	4
	12	10
	13	13
	14	14
	15	15
	15	16
	16	17
	17	18
	18	18
	18	19
	19	20
	20	20
	21	21
	22	22
	22	22
	23	23
	24	24
	25	24
	26	25
	26	26
	27	26
	28	29
	29	30
	30	30

MoCA was adjusted for the years of education. Scores that are in the shaded boxes are derived from extrapolated data.

Uncertain Spans

location	transcription	uncertainty
Top Holden 2018 table left rows	(Levodopa OFF / Levodopa ON / Other PD meds banded sub-rows including Mean (SD), (Min, max) for both Total score and Part III score across 6 timepoints)	The full Levodopa OFF/ON sub-table at the very top of the page is partially cut off above the body crop and the leftmost row labels have a coloured pink/red highlight band; numeric body cells are read as printed. Several body cells have OCR-ambiguous decimal commas (e.g. “(13.0, 70.0)”) preserved verbatim.
MoCA → MMSE conversion table	top six rows of “MoCA Total Adjusted” column	The leftmost MoCA Total column header is partly clipped at left edge of the source table; values for the column are not visible in this capture. The shaded box rows (rows ≤ 16 / 17 in the van Steenoven column) preserve the source highlight via empty MoCA-Total cells.
Milestone-based approach right cell	AD/PD 2023Raphael T.Gerraty's poster and RNA	The right column appears to combine a poster reference and a stand-alone “RNA” tag from the source; the spacing of 2023Raphael is rendered as a single token in the source text.