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Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan
Luo J, Agboola F, Grant E, Morris JC, Masters CL, Albert MS, Johnson SC, McDade EM et al.. Brain : a journal of neurology, 2022-12-01
Topic: Amyloid, tau and blood-test diagnosis
The temporal evolutions and relative orderings of Alzheimer disease biomarkers, including CSF amyloid-β42 (Aβ42), Aβ40, total tau (Tau) and phosphorylated tau181 (pTau181), standardized uptake value ratio (SUVR) from the molecular imaging of cerebral fibrillar amyloid-β with PET using the 11C-Pittsburgh Compound-B (PiB), MRI-based hippocampal volume and cortical thickness and cognition have been hypothesized but not yet fully tested with longitudinal data for all major biomarker modalities among cognitively normal individuals across the adult lifespan starting from 18 years. By leveraging a large harmonized database from 8 biomarker studies with longitudinal data from 2609 participants in cognition, 873 in MRI biomarkers, 519 in PET PiB imaging and 475 in CSF biomarkers for a median follow-up of 5-6 years, we estimated the longitudinal trajectories of all major Alzheimer disease biomarke
Key findings
- By leveraging a large harmonized database from 8 biomarker studies with longitudinal data from 2609 participants in cognition, 873 in MRI biomarkers, 519 in PET PiB imaging and 475 in CSF biomarkers for a median follow-up of 5-6 years, we estimated the longitudinal trajectories of all major Alzheimer disease biomarkers as functions of baseline age that spanned from 18 to 103 years, located the baseline age window at which the longitudinal rates of change accelerated and further examined possible modifying effects of apolipoprotein E (APOE) genotype.
- We observed that participants 18-45 years at baseline exhibited learning effects on cognition and unexpected directions of change on CSF and PiB biomarkers.
- The earliest acceleration of longitudinal change occurred for CSF Aβ42 and Aβ42/Aβ40 ratio (with an increase) and for Tau, and pTau181 (with a decrease) at the next baseline age interval of 45-50 years, followed by an accelerated increase for PiB SUVR at the baseline age of 50-55 years and an accelerated decrease for hippocampal volume at the baseline age of 55-60 years and finally by an accelerated decline for cortical thickness and cognition at the baseline age of 65-70 years.
- Another acceleration in the rate of change occurred at the baseline age of 65-70 years for Aβ42/Aβ40 ratio, Tau, pTau181, PiB SUVR and hippocampal volume.
Why it matters
This large longitudinal study estimated the trajectories and ordering of Alzheimer's disease biomarkers across the adult lifespan in cognitively normal individuals. It describes how biomarkers change over time, not how to treat, cure, or prevent Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Participants2,609
- Evidence strengthModerate
How this study scored 65/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 62 of the 96 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,609 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 | 4 / 7 | Cited 47 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 14 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35925685) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 62 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 62 of the 96 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Luo, J., Agboola, F., Grant, E., Morris, J. C., Masters, C. L., Albert, M. S., et al. (2022). Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan. Brain : a journal of neurology. https://doi.org/10.1093/brain/awac238
Vancouver
Luo J, Agboola F, Grant E, Morris JC, Masters CL, Albert MS, et al. Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan. Brain : a journal of neurology. 2022. doi:10.1093/brain/awac238. PMID: 35925685.
BibTeX
@article{luo2022-35925685,
author = {Luo, J. and Agboola, F. and Grant, E. and Morris, J. C. and Masters, C. L. and Albert, M. S. and Johnson, S. C. and McDade, E. M. and others},
title = {{Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan}},
journal = {Brain : a journal of neurology},
year = {2022},
doi = {10.1093/brain/awac238},
pmid = {35925685},
url = {https://doi.org/10.1093/brain/awac238}
}
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