GBA vs UPDRS vs MOCA (full literature comparison)
Top longitudinal block (continued)
| GBA geneotype vs UPDRS | GBA activity vs UPDRS | GBA geneotype vs GBA activity | GBA genotype vs Cognition | GBA activity vs Cognition | |
|---|---|---|---|---|---|
| Longitudinal |
(Maple-Grødem, 2021 #2654) fig2., fig3 (sample size) 20240416 (Maple-Grødem, 2021 #2654) js calculation UPDRS III progression: 'difference between GBA-PD vs non-GBA-PD in progression rate' : ~29% (js calcu) GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% confidence interval [CI] 1.1-2.0) and motor symptoms (2.2 points per year, 95% CI 1.3-3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9-1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1-1.6, p = 0.007) |
?????? Hamid to model? Note) longitudinal GBA activity change in iPD: (Alcalay, 2020 #2656) fig2&3 (suppl 엑셀의 raw data 일일이 보면 우측 Huh 2020 자료처럼 GBA-PD에선 longi decrease있는지 확인가능하겠네. | (Huh 2020' ) fig 3 | (Ren, 2023 #2657) fig2 | (Oftedal, 2023 #2655) fig 2 |
| (Ren, 2023 #2657) fig1 , Supplementary Figure 2 (Sphagetti plot), (from fig1) 'difference between GBA-PD vs non-GBA-PD in progression rate' : ~38% (js calcu) | |||||
| Cross-sectional | 2021 Avenali phd dissertation FIG3 | (Alcalay, 2020 #2656) fig4 | (Alcalay, 2020 #2656) fig1 | 2021 Avenali phd dissertation FIG3 | |
| (Omer, 2022 #2659) Biogen) Cf) UPDRS 와 MOCA 가 GBA-PD vs ipd 간 = | (Alcalay, 2020 #2656) | Huh 2020' fig2 | (Omer, 2022 #2659, Biogen) Cf) UPDRS 와 MOCA 가 GBA-PD vs ipd 간 = |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Activity row / Hamid placeholder | ?????? Hamid to model? | reads as written; preserved verbatim. |
Clinical dev Scenarios
- GBA w MCI/Dementia: MOCA slope
- GBA w/o Dementia: development of dementia (proportion, or Survival Analysis for the Time to Develop Dementia)
Task: 5/11 proportion of PD-MCI and PDD in GBA-PD!
Task: 찾자! proportion of PD-MCI and PDD in GBA-PD!
2021 Avenali phd dissertation FIG3
genotype / Activity / Activity-DBS rows
| genotype | Activity | Activity-DBS | |
|---|---|---|---|
| activity | (Huh 2020') fig 2, | (Alcalay, 2020 #2656) fig? | (Alcalay, 2020 #2656) DBS, fig1 |
| (Omer, 2022 #2659) Biogen, (102 GBA-PD [73 mGBA, 16 sGBA, 13 vGBA], 38 LRRK2-PD, and 30 iPD) no difference of GBA activity between severe vs mild | |||
| conclusion | Large overlap between genotype (severe or mild) vs activity | ||
| UPDRS / Cross-sectional | (Omer, 2022 #2659, Biogen, 'BEAT-PD' ) (102 GBA-PD, 38 LRRK2-PD, and 30 idiopathic PD) | Cf) UPDRS 와 MOCA 가 GBA-PD vs ipd 간 = | PPMI! (large n, (Alcalay, 2020 #2656) DBS, table 3 |
UPDRS longitudinal
| genotype | Activity | Activity-DBS | |
|---|---|---|---|
| Longi (6 y f/u) | PPMI (Caminiti, 2022 #2706) UPDRS total, and UPDRS III: slower! | ||
| Longi (7 years f/u) | (Maple-Grødem, 2021 #2654) Norwegian ParkWest study, the Swedish NYPUM study, and the Scottish PINE study, 3 prospective population-based longitudinal incidence studies of PD GBA-PD: 53명, iPD 387명 fig2., fig3 (sample size) | ||
| 387 iPD (age at baseline 70.3 ± 9.5 years; 60.2% male) and 53 GBA carriers, GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% [CI] 1.1-2.0) and motor symptoms (2.2 points per year, 95% CI 1.3-3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9-1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1-1.6, p = 0.007) | |||
| 이걸로 내 계산 ADL (UPDRS II): 33% faster, MOTOR (UPDRS III): 40.9% faster Severe vs mild 비교X | |||
| Longi, updrs II and III |
(Ren, 2023 #2657) 43 GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (fig1, Sup Figure 2 (sphagetti)) The estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19) js 40% faster decline; 0.29 (0.04) points/year; js 45% faster decline, respectively]. | ||
| GBA activity vs UPDRS |
?????? Hamid to model? Note) 'PPMI' longitudinal GBA activity change in iPD: (Alcalay, 2020 #2656) fig2 (sphagetti) &3 (sphagetti) (suppl 엑셀의 raw data 일일이 보면 우측 Huh 2020 자료처럼 GBA-PD에선 longi decrease있는지 확인가능하겠네. | ||
| Longi | 2021 Avenali phd dissertation FIG3 | PPMI, genotype vs updrs progression? 어딘가 논문 있을텐데, Jonghun 부탁? | PPMI, Activity vs updrs progression? 어딘가 논문 있을텐데, Jonghun 있나? |
| Conclusion | Longitudinally, i) enough differentiation between GBA-PD vs iPD, ii) even larger differentiation between severe vs mild (PPMI-종훈으로 validation하자) | ||
Cognition rows
| genotype | Activity | Activity-DBS | |
|---|---|---|---|
| Cognition / Cross-sectional | (Omer, 2022 #2659, Biogen) Cf) UPDRS 와 MOCA 가 GBA-PD vs ipd 간 = | 2021 Avenali phd dissertation FIG3 | PPMI! Large n, (Alcalay, 2020 #2656) table 3, ONLY trend |
| Cross-sectional: PPMI | Huh, 2021) iPD 227, GBA-PD 44, MOCA: 27.0 vs 28.0 (26.0-29.0) 이게 interquartile range 니까 25% 정도가 <26 이라는 거네. | ||
| (Koros, 2021 #2721) PD 369, GBA-PD 120, MOCA: 27.17 vs 25.3 (4.03) | |||
| (Simuni, 2020 #2722) PD 361, GBA-PD 80, MOCA: 26.2 (3.2, 이건 y2!) vs 26.1 (2.9) 이거보면 <50%이고 그중 대부분은 mci 겟네. | |||
| (Jeong, 2023 #2723) PD 239, GBA-PD 61, MOCA: 26.6 vs 26.0 (2.6) 이거보면 <50%이고 그중 대부분은 mci 겟네. | |||
| Longi (6 y f/u) | PPMI (Caminiti, 2022 #2706) MOCA: BL-y2: =, Y2-Y6: 오히려 3% slower, after y6: 18% faster | ||
| Longi, pooled | HBS, DATATOP, DIGPD, CamPaIGN, PICNICS, PROPARK, PreCEPT, Only Neuropathic Gaucher's Mutations Accelerate Cognitive Decline | ||
| Longi |
(Ren, 2023 #2657) GBA-PD (n = 43), Severe GBA-PD (n = 16) fig2 The estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); 0.29 (0.04) points/year; respectively]. | ||
| GBA activity vs Cognition | (Oftedal, 2023 #2655) CSF GBA activity! Norwegian ParkWest study, 117 patients with PD (including 12 GBA nonsynonymous variant carriers) and 50 control participants fig 2 | ||
Motor + Cognition / NfL
| content | |
|---|---|
| Longi (same cohort) | (Winder-Rhodes 2015) UK Cambridgeshire & PICNICS, early PD (H&Y 1.8 at baseline) Time to dementia, time to H&Y3 |
| Longi (same cohort) | (Stoker, 2020 #2789) early PD (H&Y 2.0 at baseline) 48 GBA-PD, ↑ time to HY3, ↑ time to dementia (UPDRS는 언급X), ↑ The risk (proportion일것) of progression to postural instability, |
| Conclusion | PPMI, genotype vs MOCA progression? 어딘가 논문 있을텐데, Jonghun 있나? PPMI, Activity vs MOCA progression? 어딘가 논문 있을텐데, Jonghun 있나? |
| r+cog / Longi | (Brockmann 2015) Germany, Tubingen 33 GBA-PD, 27 iPD. Dis duration=9.8y UPDRS III, MOCA, Mood (BDI-II) all rapid progressed |
| Longi, pooled |
(Ortega, 2021 #2808) msbi, HBS, PDBP, LCC, 128 GBA-PD, 909 iPD, BL dis duration=6.9y, ↑ MDS-UPDRS III (1.15 (0.16) points/y for idiopathic PD, vs 1.64 (0.26) points/y for GBA PD (괄호는 SE), 30% difference), ↑ MOCA (-0.29 (0.05) points/y for idiopathic PD, -0.52 (0.09) points/y for GBA PD, 44% difference!) |
| Retrospective | (Cilia 2016) Italy, 1982 wildtype PD and 123 with GBA mutations, dis duration at last assessment=~12y. ↑ dementia development, ↑ UPDRS I, ↑ UPDRS II, ↑ UPDRS III, =UPDRS IV, ↑ H&Y 3 |
| NfL / Cross-sectional | (Yang, 2023) PPMI, 다음 세 군간 차이 X. HC 11.84, iPD 13.18, GBA-PD 14.87 |
| NfL / Longi (PPMI) | (Yang, 2023) PPMI, no difference in the longitudinal change of NfL between iPD (1.10 pg/mL per year) and GBA-PD (0.98 pg/mL Suggesting, that relationship between GBA mutation and dementia was not mediated by baseline or longitudinal NfL |