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Biomarkers of Underlying Alzheimer Disease Pathology & Neuro-inflammation, But Not Peripheral Inflammation, Predict Disease Clinically-Significant Progression in Mild-Moderate Alzheimer's Disease
Adam H. Dyer, Helena Dolphin, Tara Kenny, BRIAN A. LAWLOR, Cliona O’Farrelly, Nollaig M. Bourke, Seán Kennelly, The NILVAD Study Group. Age and Ageing, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract Background Novel prognostic biomarkers are urgently needed in older adults with Alzheimer Disease (AD). Peripheral inflammation, systemic inflammatory events (SIEs) and delirium are increasingly recognised as AD risk factors, but their impact on progression in established AD and temporal relationships with AD progression remains unclear. Further, whether SIEs, adverse events and delirium interact with peripheral inflammation to accelerate AD is unknown. Methods We analysed >1,000 plasma/cerebrospinal fluid samples from 333 patients with mild to moderate dementia due to AD with 18-months of follow-up. Ten cytokines/chemokines (IFN-γ, IL-6, IL-10, IL-12p70, IL-17A, TNF-α, Eotaxin, IP-10, MCP-1, MIP-1β) were quantified at baseline, 12, and 18-months using ultra-sensitive immunoassays. Baseline neurodegenerative biomarkers (p-tau217, p-tau181, t-tau, Neurofilament Light [NfL], Glial Fibrillary Acidic Protein [GFAP]) were measured using validated immunoassays. Clinical progression was assessed using Clinical Dementia Rating Scale (CDR-Sb). Results of linear and logistic regression models are reported as Beta Coefficients (B) and Odds Ratios (OR), respectively, with 95% Confidence Intervals and p-values and adjustment for important clinical confounders. Results Baseline peripheral inflammatory biomarkers (particularly IL-6 and IP-10) correlated significantly with age and sociodemographic factors but not AD severity. Peripheral inflammatory biomarkers remained remarkably stable over 18-months despite clinical-significant decline. Conversely, plasma biomarkers of AD pathophysiology (p-tau217) and neuro-inflammation (GFAP) at baseline strongly predicted accelerated AD progression (p-tau217: B:0.54, 0.18-1.08, p=0.02; GFAP: B:0.53, 0.18-0.90, p=0.002). Single (OR:2.63, 1.55-3.71, p<0.001) or multiple episodes of delirium (OR:3.45, 1.77-5.13, p<0.001), but not SIEs or adverse events, predicted greater progression on the CDR-Sb. Conclusion Biomarkers specific to AD pathology (p-tau217, GFAP) rather than peripheral inflammation had robust prognostic value in established AD. Delirium was consistently associated with clinically-meaningful decline, highlighting the importance of delirium prevention efforts in older adults with AD. Our findings add strong evidence supporting the prognostic utility of p-tau217 and GFAP in older adults with established AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dyer, A. H., Dolphin, H., Kenny, T., LAWLOR, B. A., O’Farrelly, C., Bourke, N. M., et al. (2025). Biomarkers of Underlying Alzheimer Disease Pathology & Neuro-inflammation, But Not Peripheral Inflammation, Predict Disease Clinically-Significant Progression in Mild-Moderate Alzheimer's Disease. Age and Ageing. https://doi.org/10.1093/ageing/afaf318.009
Vancouver
Dyer AH, Dolphin H, Kenny T, LAWLOR BA, O’Farrelly C, Bourke NM, et al. Biomarkers of Underlying Alzheimer Disease Pathology & Neuro-inflammation, But Not Peripheral Inflammation, Predict Disease Clinically-Significant Progression in Mild-Moderate Alzheimer's Disease. Age and Ageing. 2025. doi:10.1093/ageing/afaf318.009.
BibTeX
@article{dyer2025-80aa2d8b,
author = {Dyer, Adam H. and Dolphin, Helena and Kenny, Tara and LAWLOR, BRIAN A. and O’Farrelly, Cliona and Bourke, Nollaig M. and Kennelly, Seán and {The NILVAD Study Group}},
title = {{Biomarkers of Underlying Alzheimer Disease Pathology \& Neuro-inflammation, But Not Peripheral Inflammation, Predict Disease Clinically-Significant Progression in Mild-Moderate Alzheimer's Disease}},
journal = {Age and Ageing},
year = {2025},
doi = {10.1093/ageing/afaf318.009},
url = {https://doi.org/10.1093/ageing/afaf318.009}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Results of linear and logistic regression models are reported as Beta Coefficients (B) and Odds Ratios (OR), respectively, with 95% Confidence Intervals and p-values and adjustment for important clinical confounders.
- Results Baseline peripheral inflammatory biomarkers (particularly IL-6 and IP-10) correlated significantly with age and sociodemographic factors but not AD severity.
- Peripheral inflammatory biomarkers remained remarkably stable over 18-months despite clinical-significant decline.
- Delirium was consistently associated with clinically-meaningful decline, highlighting the importance of delirium prevention efforts in older adults with AD.
- Our findings add strong evidence supporting the prognostic utility of p-tau217 and GFAP in older adults with established AD.
Why it matters
In 333 patients with mild to moderate Alzheimer's disease followed for 18 months, blood markers of peripheral inflammation did not predict clinically significant progression, while biomarkers of underlying Alzheimer's pathology and neuroinflammation did. Peripheral inflammatory markers stayed stable over 18 months even as patients declined, suggesting they are not useful for tracking disease progression in established Alzheimer's disease.
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Study details
- Participants333
- Effect sizeOR:2.63; OR:3.45
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design and randomized / 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 37 of the 96 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Age and Ageing) |
| Journal's citation record | 2 / 4 | Age and Ageing: journal h-index 231 (OpenAlex, 2026-10-29) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 333 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 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 | 1 / 3 | Trinity College Dublin: institution h-index 926 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 37 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 37 of the 96 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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