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Symptom-Guided Blood Biomarker Testing for Alzheimer's Disease
Matthew D Howe, Benjamin S Zide, Kaleen Hayes, Daliah Ross, Megan S Barker, Zachary J Kunicki, James Rudolph, Edward Huey. Dementia and geriatric cognitive disorders, 2026-10-12
Topic: Plasma and spinal-fluid biomarkers
Introduction Blood-based biomarkers can accurately detect Alzheimer's disease (AD) pathology, but symptom-guided testing approaches are understudied. This study evaluated the utility of early symptom and biomarker changes in predicting cognitive decline due to AD. Methods We analyzed data from the Alzheimer's Disease Neuroimaging Initiative-2 (development, n=603) and -3 (validation, n=378). The primary outcome was 4-year progression to mild cognitive impairment or dementia associated with amyloid-beta neuropathology. Machine learning estimated baseline symptom burden from subjective ratings. Logistic regression calculated area under the curve (AUC), relative risk, and time-to-event. Results Symptom burden predicted clinical progression (AUC=0.79), which further improved with blood biomarkers (AUC=0.90). Participants with elevated symptoms and biomarkers had a progression incidence of 72.1% and a 19-fold higher progression risk. Findings replicated in validation. Conclusion Findings underscore the potential of pairing symptoms and biomarkers to more efficiently and accurately detect AD cases at risk of clinical progression. Trial Parent study registrations: NCT01231971; NCT02854033.
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APA 7th
Howe, M. D., Zide, B. S., Hayes, K., Ross, D., Barker, M. S., Kunicki, Z. J., et al. (2026). Symptom-Guided Blood Biomarker Testing for Alzheimer's Disease. Dementia and geriatric cognitive disorders. https://doi.org/10.1159/dem/aciag010
Vancouver
Howe MD, Zide BS, Hayes K, Ross D, Barker MS, Kunicki ZJ, et al. Symptom-Guided Blood Biomarker Testing for Alzheimer's Disease. Dementia and geriatric cognitive disorders. 2026. doi:10.1159/dem/aciag010. PMID: 42862762.
BibTeX
@article{howe2026-42862762,
author = {Howe, Matthew D and Zide, Benjamin S and Hayes, Kaleen and Ross, Daliah and Barker, Megan S and Kunicki, Zachary J and Rudolph, James and Huey, Edward},
title = {{Symptom-Guided Blood Biomarker Testing for Alzheimer's Disease}},
journal = {Dementia and geriatric cognitive disorders},
year = {2026},
doi = {10.1159/dem/aciag010},
pmid = {42862762},
url = {https://doi.org/10.1159/dem/aciag010}
}
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Key findings
- The primary outcome was 4-year progression to mild cognitive impairment or dementia associated with amyloid-beta neuropathology.
- Results Symptom burden predicted clinical progression (AUC=0.79), which further improved with blood biomarkers (AUC=0.90).
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Study details
- Participants603
- Effect sizeAUC=0.79; AUC=0.90; 72.1%
- Evidence strengthLow
How this study scored 59/100
Published in a peer-reviewed journal. Scored zero for study design 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, multi-centre collaboration and free to read, so those were left out: it earned 33 of the 56 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Dementia and geriatric cognitive disorders) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 603 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 | — / 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 42862762) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 33 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 33 of the 56 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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