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Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women
Shadyab AH, Zhang B, LaCroix AZ, Mielke MM, Resnick SM, Nguyen S, Ferrucci L, Libermann TA, Ngo L, Casanova R, et al.. JAMA Network Open, 2026-03-02
Topic: Brain proteins, microglia and lab models
Results Among 2766 participants (mean [SD] age, 69.9 [3.8] years; 486 [17.9%] Black, 196 [7.1%] Hispanic, and 2007 [73.9%] White), 1311 developed the combined end point of MCI or dementia (849 participants with MCI and 752 participants with dementia). Every 1-SD increase in log2-transformed p-tau217 was associated with incident MCI or dementia (HR, 2.43; 95% CI, 2.18-2.71) and each individual outcome (MCI: HR, 1.94; 95% CI, 1.72-2.20; dementia: HR, 3.17; 95% CI, 2.79-3.61). Associations of p-tau217 with dementia were larger in magnitude for women randomized to estrogen plus progestin (HR, 4.18; 95% CI, 3.41-5.13) vs placebo (HR, 3.07; 95% CI, 2.41-3.91) (P for interaction = .04) but did not significantly vary by estrogen alone vs placebo. P-tau217 associations with MCI or dementia were larger in magnitude for women older than 70 years (P for interaction = .04), APOE ε4 carriers (P for interaction = .02), and White women compared with Black women (P for interaction Conclusions and relevance In this cohort study of cognitively unimpaired older women, p-tau217 was associated with incident MCI or dementia up to 25 years later. These findings suggest that age, race, APOE ε4, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.
Key findings
- Results Among 2766 participants (mean [SD] age, 69.9 [3.8] years; 486 [17.9%] Black, 196 [7.1%] Hispanic, and 2007 [73.9%] White), 1311 developed the combined end point of MCI or dementia (849 participants with MCI and 752 participants with dementia).
- Every 1-SD increase in log2-transformed p-tau217 was associated with incident MCI or dementia (HR, 2.43; 95% CI, 2.18-2.71) and each individual outcome (MCI: HR, 1.94; 95% CI, 1.72-2.20; dementia: HR, 3.17; 95% CI, 2.79-3.61).
- Associations of p-tau217 with dementia were larger in magnitude for women randomized to estrogen plus progestin (HR, 4.18; 95% CI, 3.41-5.13) vs placebo (HR, 3.07; 95% CI, 2.41-3.91) (P for interaction = .04) but did not significantly vary by estrogen alone vs placebo.
- P-tau217 associations with MCI or dementia were larger in magnitude for women older than 70 years (P for interaction = .04), APOE ε4 carriers (P for interaction = .02), and White women compared with Black women (P for interaction < .001).
- These findings suggest that age, race, APOE ε4, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.
Why it matters
In this cohort of older women, higher plasma p-tau217 was associated with developing MCI or dementia up to 25 years later. The authors say age, race, APOE ε4, and hormone therapy use should be considered when examining these associations.
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Study details
- Study designcohort
- Participants2,766
- Effect sizeHR 2.43 (95% CI 2.18-2.71) for MCI or dementia per SD of plasma p-tau217; dementia HR 3.17 (2.79-3.61)
- Evidence strengthModerate
Limitations
Women only; blood stored for about 25 years before assay; single baseline measurement; relatively small Black and Hispanic subgroups; MCI and dementia adjudicated within the trial rather than by biomarker-confirmed diagnosis.
How this study scored 69/100
Published in a leading specialty journal, and it is a cohort study following people over time. We have no data on free to read, so that was left out: it earned 68 of the 98 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Network Open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,766 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 37.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Linda K. McEvoy: h-index 69 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41805953) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 68 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 68 of the 98 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1001/jamanetworkopen.2026.1295
- PubMed: 41805953
- Original source →
- Free full text: PubMed Central →
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
Shadyab, A. H., Zhang, B., LaCroix, A. Z., Mielke, M. M., Resnick, S. M., Nguyen, S., et al. (2026). Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2026.1295
Vancouver
Shadyab AH, Zhang B, LaCroix AZ, Mielke MM, Resnick SM, Nguyen S, et al. Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women. JAMA Network Open. 2026. doi:10.1001/jamanetworkopen.2026.1295. PMID: 41805953.
BibTeX
@article{shadyab2026-41805953,
author = {Shadyab, A. H. and Zhang, B. and LaCroix, A. Z. and Mielke, M. M. and Resnick, S. M. and Nguyen, S. and Ferrucci, L. and Libermann, T. A. and Ngo, L. and Casanova, R. and others},
title = {{Plasma Phosphorylated Tau 217 and Incident Mild Cognitive Impairment and Dementia in Older Women}},
journal = {JAMA Network Open},
year = {2026},
doi = {10.1001/jamanetworkopen.2026.1295},
pmid = {41805953},
url = {https://doi.org/10.1001/jamanetworkopen.2026.1295}
}
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