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Precision medicine analysis of heterogeneity in individual-level treatment response to amyloid beta removal in early Alzheimer's disease
Pang M, Gabelle A, Saha-Chaudhuri P, Huijbers W, Gafson A, Matthews PM, Tian L, Rubino I et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023-10-26
Topic: Amyloid, tau and blood-test diagnosis
Introduction Alzheimer's disease (AD) is a neurological disorder with variability in pathology and clinical progression. AD patients may differ in individual-level benefit from amyloid beta removal therapy. Methods Random forest models were applied to the EMERGE trial to create an individual-level treatment response (ITR) score which represents individual-level benefit of high-dose aducanumab relative to the placebo. This ITR score was used to test the existence of heterogeneity in treatment effect (HTE). Results We found statistical evidence of HTE in the Clinical Dementia Rating-Sum of Boxes (CDR-SB;P = 0.034). The observed CDR-SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (P = 0.020). Of note, the highest treatment responders had lower hippocampal volume, higher plasma phosphorylated tau 181 and a shorter duration of clinical AD at baseline. Discussion This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development. Highlights Emerging trials have shown a population-level benefit from amyloid beta (Aβ) removal in slowing cognitive decline in early Alzheimer's disease (AD). This work demonstrates significant heterogeneity of individual-level treatment effect of aducanumab in early AD. The greatest clinical responders to Aβ removal therapy have a pattern of more severe neurodegenerative process.
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APA 7th
Pang, M., Gabelle, A., Saha-Chaudhuri, P., Huijbers, W., Gafson, A., Matthews, P. M., et al. (2024). Precision medicine analysis of heterogeneity in individual-level treatment response to amyloid beta removal in early Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13431
Vancouver
Pang M, Gabelle A, Saha-Chaudhuri P, Huijbers W, Gafson A, Matthews PM, et al. Precision medicine analysis of heterogeneity in individual-level treatment response to amyloid beta removal in early Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.13431. PMID: 37882364.
BibTeX
@article{pang2024-37882364,
author = {Pang, M. and Gabelle, A. and Saha-Chaudhuri, P. and Huijbers, W. and Gafson, A. and Matthews, P. M. and Tian, L. and Rubino, I. and others},
title = {{Precision medicine analysis of heterogeneity in individual-level treatment response to amyloid beta removal in early Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.13431},
pmid = {37882364},
url = {https://doi.org/10.1002/alz.13431}
}
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Key findings
- Results We found statistical evidence of HTE in the Clinical Dementia Rating-Sum of Boxes (CDR-SB;P = 0.034).
- The observed CDR-SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (P = 0.020).
- This work demonstrates significant heterogeneity of individual-level treatment effect of aducanumab in early AD.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37882364) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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