Home › Research › Tau biomarkers
Midlife and Late-Life Alzheimer Disease Blood Biomarkers and 11-Year Cognitive Decline
Smith JR, Pike JR, Lu Y, Walker KA, Sullivan KJ, Windham BG, Thyagarajan B, Mielke MM et al.. Neurology, 2026-10-16
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Plasma biomarkers of Alzheimer disease (AD) neuropathology (amyloid-β42 to amyloid β40 [Aβ42/40] ratio, phosphorylated tau at threonine [p-tau181]), neurodegeneration (neurofilament light [NfL]), and neuroinflammation (glial fibrillary acidic protein [GFAP]) in late-life are associated with cognitive decline. Whether these biomarkers in midlife are predictive of subsequent cognitive decline, and whether they are associated with different cognitive domains, is uncertain. Results In 1,515 included participants, 60.7% (n = 920) were female and 25.5% (n = 387) were Black. Each SD increase in p-tau181 in midlife was significantly associated with faster late-life memory decline (β = -0.030 [95% CI -0.059 to -0.001] SD. Midlife Aβ42/40, NfL, and GFAP were not associated with subsequent decline in any cognitive domain. In late-life, p-tau181, NfL, and GFAP were significantly associated with faster decline in different cognitive domains, with the strongest associations seen with memory (β = -0.091 [95% CI -0.123 to -0.058] SD; β = -0.064 [95% CI -0.106 to -0.023] SD; and β = -0.048 [95% CI -0.082 to -0.013] SD, respectively). Discussion Midlife p-tau181 was associated with faster 11-year memory decline beginning 20 years later in the ARIC cohort, which underscores a potentially long prodromal phase of cognitive decline that could precede dementia onset. In late-life, biomarkers for AD, neurodegeneration, and neuroinflammation were associated with faster decline across different cognitive domains, but associations remained strongest for p-tau181 and memory.
Key findings
- Background and objectives Plasma biomarkers of Alzheimer disease (AD) neuropathology (amyloid-β42 to amyloid β40 [Aβ42/40] ratio, phosphorylated tau at threonine [p-tau181]), neurodegeneration (neurofilament light [NfL]), and neuroinflammation (glial fibrillary acidic protein [GFAP]) in late-life are associated with cognitive decline.
- Whether these biomarkers in midlife are predictive of subsequent cognitive decline, and whether they are associated with different cognitive domains, is uncertain.
- Results In 1,515 included participants, 60.7% (n = 920) were female and 25.5% (n = 387) were Black.
- Each SD increase in p-tau181 in midlife was significantly associated with faster late-life memory decline (β = -0.030 [95% CI -0.059 to -0.001] SD.
- Midlife Aβ42/40, NfL, and GFAP were not associated with subsequent decline in any cognitive domain.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designprospective cohort
- Participants920
- Effect size60.7%; 25.5%
- Evidence strengthModerate
How this study scored 74/100
Published in a leading specialty journal, and it is a prospective cohort study, followed forward from enrollment. Scored zero for 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 43 of the 58 points we could judge it on, which is 74 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 prospective cohort study, followed forward from enrollment |
| 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 | 2 / 4 | 920 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 | 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 42886876) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 43 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 43 of the 58 points we could judge it on is 74 out of 100. |
| Total | 74 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Smith, JR., Pike, JR., Lu, Y., Walker, K. A., Sullivan, K. J., Windham, B. G., et al. (2026). Midlife and Late-Life Alzheimer Disease Blood Biomarkers and 11-Year Cognitive Decline. Neurology. https://doi.org/10.1212/wnl.0000000000218692
Vancouver
Smith JR, Pike JR, Lu Y, Walker KA, Sullivan KJ, Windham BG, et al. Midlife and Late-Life Alzheimer Disease Blood Biomarkers and 11-Year Cognitive Decline. Neurology. 2026. doi:10.1212/wnl.0000000000218692. PMID: 42886876.
BibTeX
@article{smith2026-42886876,
author = {Smith, JR. and Pike, JR. and Lu, Y. and Walker, K. A. and Sullivan, K. J. and Windham, B. G. and Thyagarajan, B. and Mielke, M. M. and others},
title = {{Midlife and Late-Life Alzheimer Disease Blood Biomarkers and 11-Year Cognitive Decline}},
journal = {Neurology},
year = {2026},
doi = {10.1212/wnl.0000000000218692},
pmid = {42886876},
url = {https://doi.org/10.1212/wnl.0000000000218692}
}