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Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia
Lu Y, Pike JR, Chen J, Walker KA, Sullivan KJ, Thyagarajan B, Mielke MM, Lutsey PL, Knopman D, Gottesman RF, Sharrett AR, Coresh J, et al.. JAMA, 2024-10-15
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. Results Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Conclusions and relevance Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers' association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.
Key findings
- Objective To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults.
- Results Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black.
- Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP.
- Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25).
- All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14).
Why it matters
In community-dwelling adults, midlife hypertension and diabetes were associated with faster increases in NfL and GFAP, while only Alzheimer's-specific biomarkers in midlife showed long-term associations with late-life dementia. All plasma biomarkers measured in late life were associated with late-life dementia, with NfL showing the largest association.
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Study details
- Study designcohort
- Participants1,525
- Effect sizeLate-life NfL HR 1.92 per SD (95% CI 1.72-2.14) for incident dementia; midlife p-tau181 HR 1.15 per SD
- Evidence strengthHigh
How this study scored 79/100
Published in a top-tier journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 77 of the 98 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,525 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 82 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 22.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 82 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Priya Palta: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39068543) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 77 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 77 of the 98 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Lu, Y., Pike, JR., Chen, J., Walker, K. A., Sullivan, K. J., Thyagarajan, B., et al. (2024). Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia. JAMA. https://doi.org/10.1001/jama.2024.6619
Vancouver
Lu Y, Pike JR, Chen J, Walker KA, Sullivan KJ, Thyagarajan B, et al. Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia. JAMA. 2024. doi:10.1001/jama.2024.6619. PMID: 39068543.
BibTeX
@article{lu2024-39068543,
author = {Lu, Y. and Pike, JR. and Chen, J. and Walker, K. A. and Sullivan, K. J. and Thyagarajan, B. and Mielke, M. M. and Lutsey, P. L. and Knopman, D. and Gottesman, R. F. and Sharrett, A. R. and Coresh, J. and others},
title = {{Changes in Alzheimer Disease Blood Biomarkers and Associations With Incident All-Cause Dementia}},
journal = {JAMA},
year = {2024},
doi = {10.1001/jama.2024.6619},
pmid = {39068543},
url = {https://doi.org/10.1001/jama.2024.6619}
}
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