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MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD
Jack CR, Slomkowski M, Gracon S, Hoover TM, Felmlee JP, Stewart K, Xu Y, Shiung M et al.. Neurology, 2003-01-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess the feasibility of using MRI measurements as a surrogate endpoint for disease progression in a therapeutic trial for AD. Methods A total of 362 patients with probable AD from 38 different centers participated in the MRI portion of a 52-week randomized placebo-controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself was not completed due to projected lack of efficacy on interim analysis; however, the MRI arm of the study was continued. Of the 362 subjects who underwent a baseline MRI study, 192 subjects underwent a second MRI 1 year later. Hippocampal volume and temporal horn volume were measured from the MRI scans. Results The annualized percent changes in hippocampal volume (-4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single-site studies. Correlations between the rate of MRI volumetric change and change in behavioral/cognitive measures were greater for the temporal horn than for the hippocampus. Decline over time was more consistently seen with imaging measures, 99% of the time for the hippocampus, than behavioral/cognitive measures (p < 0.001). Greater consistency in MRI than behavioral/clinical measures resulted in markedly lower estimated sample size requirements for clinical trials. The estimated number of subjects per arm required to detect a 50% reduction in the rate of decline over 1 year are: AD Assessment Scale-cognitive subscale 320; Mini-Mental Status Examination 241; hippocampal volume 21; temporal horn volume 54. Conclusion The consistency of MRI measurements obtained across sites, and the consistency between the multisite milameline data and that obtained in prior single-site studies, demonstrate the technical feasibility of using structural MRI measures as a surrogate endpoint of disease progression in therapeutic trials. However, validation of imaging as a biomarker of therapeutic efficacy in AD awaits a positive trial.
Key findings
- Results The annualized percent changes in hippocampal volume (-4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single-site studies.
Study details
- Participants362
- Effect size4.9%; 16.1%
- Evidence strengthHigh
How this study scored 62/100
Published in a leading specialty journal. Scored zero for study design 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 and institution's track record, so those were left out: it earned 38 of the 61 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| 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 | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| Sample size | 2 / 4 | 362 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| 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 | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12552040) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 38 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 38 of the 61 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Jack, C. R., Slomkowski, M., Gracon, S., Hoover, T. M., Felmlee, J. P., Stewart, K., et al. (2003). MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD. Neurology. https://doi.org/10.1212/01.wnl.0000042480.86872.03
Vancouver
Jack CR, Slomkowski M, Gracon S, Hoover TM, Felmlee JP, Stewart K, et al. MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD. Neurology. 2003. doi:10.1212/01.wnl.0000042480.86872.03. PMID: 12552040.
BibTeX
@article{jack2003-12552040,
author = {Jack, C. R. and Slomkowski, M. and Gracon, S. and Hoover, T. M. and Felmlee, J. P. and Stewart, K. and Xu, Y. and Shiung, M. and others},
title = {{MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD}},
journal = {Neurology},
year = {2003},
doi = {10.1212/01.wnl.0000042480.86872.03},
pmid = {12552040},
url = {https://doi.org/10.1212/01.wnl.0000042480.86872.03}
}
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