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Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease
Mayblyum DV, Becker JA, Jacobs HIL, Buckley RF, Schultz AP, Sepulcre J, Sanchez JS, Rubinstein ZB et al.. Neurology, 2021-06-14
Topic: Amyloid, tau and blood-test diagnosis
Objective To compare how structural MRI, fluorodeoxyglucose (FDG), and flortaucipir (FTP) PET signals predict cognitive decline in high-amyloid vs low-amyloid participants with the goal of determining which biomarker combination would result in the highest increase of statistical power for prevention trials. Methods In this prospective cohort study, we analyzed data from clinically normal adults from the Harvard Aging Brain Study with MRI, FDG, FTP, and Pittsburgh compound B (PiB)-PET acquired within a year and prospective cognitive evaluations over a mean 3-year follow-up. We focused analyses on predefined regions of interest: inferior temporal, isthmus cingulate, hippocampus, and entorhinal cortex. Cognition was assessed with the Preclinical Alzheimer's Cognitive Composite. We evaluated the association between biomarkers and cognitive decline using linear mixed-effect models with random intercepts and slopes, adjusting for demographics. We generated power curves simulating prevention trials. Results Data from 131 participants (52 women, age 73.98 ± 8.29 years) were analyzed in the study. In separate models, most biomarkers had a closer association with cognitive decline in the high-PiB compared to the low-PiB participants. A backward stepwise regression including all biomarkers demonstrated that only neocortical PiB, entorhinal FTP, and entorhinal FDG were independent predictors of subsequent cognitive decline. Power analyses revealed that using both high PiB and low entorhinal FDG as inclusion criteria reduced 3-fold the number of participants needed in a hypothetical trial compared to using only high PiB. Discussion In preclinical Alzheimer disease, entorhinal hypometabolism is a strong and independent predictor of subsequent cognitive decline, making FDG a potentially useful biomarker to increase power in clinical trials. Classification of evidence This study provides Class II evidence that in people with preclinical Alzheimer disease, entorhinal hypometabolism identified by FDG-PET is predictive of subsequent cognitive decline.
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APA 7th
Mayblyum, D. V., Becker, J. A., Jacobs, H. I. L., Buckley, R. F., Schultz, A. P., Sepulcre, J., et al. (2021). Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease. Neurology. https://doi.org/10.1212/wnl.0000000000012108
Vancouver
Mayblyum DV, Becker JA, Jacobs HIL, Buckley RF, Schultz AP, Sepulcre J, et al. Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease. Neurology. 2021. doi:10.1212/wnl.0000000000012108. PMID: 33952655.
BibTeX
@article{mayblyum2021-33952655,
author = {Mayblyum, D. V. and Becker, J. A. and Jacobs, H. I. L. and Buckley, R. F. and Schultz, A. P. and Sepulcre, J. and Sanchez, J. S. and Rubinstein, Z. B. and others},
title = {{Comparing PET and MRI Biomarkers Predicting Cognitive Decline in Preclinical Alzheimer Disease}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000012108},
pmid = {33952655},
url = {https://doi.org/10.1212/wnl.0000000000012108}
}
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Key findings
- Objective To compare how structural MRI, fluorodeoxyglucose (FDG), and flortaucipir (FTP) PET signals predict cognitive decline in high-amyloid vs low-amyloid participants with the goal of determining which biomarker combination would result in the highest increase of statistical power for prevention trials.
- Results Data from 131 participants (52 women, age 73.98 ± 8.29 years) were analyzed in the study.
- In separate models, most biomarkers had a closer association with cognitive decline in the high-PiB compared to the low-PiB participants.
- A backward stepwise regression including all biomarkers demonstrated that only neocortical PiB, entorhinal FTP, and entorhinal FDG were independent predictors of subsequent cognitive decline.
- Power analyses revealed that using both high PiB and low entorhinal FDG as inclusion criteria reduced 3-fold the number of participants needed in a hypothetical trial compared to using only high PiB.
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Study details
- Study designcohort study
- Participants131
- Evidence strengthModerate
How this study scored 67/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported 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 39 of the 58 points we could judge it on, which is 67 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 | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 131 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 33952655) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 39 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 39 of the 58 points we could judge it on is 67 out of 100. |
| Total | 67 / 100 | — |
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