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Peripheral biomarkers associated with apathy and predicting response to methylphenidate: Secondary analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET2) study
Krushnaa Sankhe, Myuri T. Ruthirakuhan, Ana C. Andreazza, Olga Brawman‐Mintzer, Suzanne Craft, Nathan Herrmann, Zahinoor Ismail, Alan J. Lerner et al.. International Psychogeriatrics, 2026-01-01
Topic: Amyloid, tau and blood-test diagnosis
In the ADMET2 biomarker subset (n = 44, MPH:21, age:75 years, MMSE:20.2), higher baseline TNF was associated with higher M6 NPI-A [B(SE)= 6.86 (1.71), p = .0003], and multivariable models found lower baseline TNF [B(SE)= 8.28(1.61), p < .001] and higher baseline S100B [B(SE)= -6.41(1.95), p = .002] were associated with lower M6 NPI-A. Exploratory analyses suggested that higher baseline NfL significantly interacted with treatment to predict lower M6 NPI-A [B(SE)= -8.36(4.21), p = .05], only when adjusting for cognition. MPH remitters had lower baseline TNF [B(SE)= -0.27(0.10), p = .02], higher baseline NfL [B(SE)= 0.33(0.14), p = .03], and a greater decrease in IL-6 [B(SE)= -0.44 (0.17), p = .02]. Inflammatory and neuronal injury biomarkers may have prognostic value and may potentially inform treatment response and remission outcomes in apathy. Apathy in Dementia Methylphenidate Trial 2 (ADMET2), NCT02346201, https://clinicaltrials.gov/study/NCT02346201.
Key findings
- In the ADMET2 biomarker subset (n = 44, MPH:21, age:75 years, MMSE:20.2), higher baseline TNF was associated with higher M6 NPI-A [B(SE)= 6.86 (1.71), p = .0003], and multivariable models found lower baseline TNF [B(SE)= 8.28(1.61), p < .001] and higher baseline S100B [B(SE)= -6.41(1.95), p = .002] were associated with lower M6 NPI-A.
- Exploratory analyses suggested that higher baseline NfL significantly interacted with treatment to predict lower M6 NPI-A [B(SE)= -8.36(4.21), p = .05], only when adjusting for cognition.
- MPH remitters had lower baseline TNF [B(SE)= -0.27(0.10), p = .02], higher baseline NfL [B(SE)= 0.33(0.14), p = .03], and a greater decrease in IL-6 [B(SE)= -0.44 (0.17), p = .02].
- Inflammatory and neuronal injury biomarkers may have prognostic value and may potentially inform treatment response and remission outcomes in apathy.
- Apathy in Dementia Methylphenidate Trial 2 (ADMET2), NCT02346201, https://clinicaltrials.gov/study/NCT02346201.
Why it matters
In a secondary analysis of 44 participants from a methylphenidate trial for apathy in dementia, baseline levels of inflammatory and neuronal injury markers (TNF, S100B, NfL, IL-6) were associated with apathy outcomes and with response to methylphenidate. These exploratory findings suggest biomarkers may one day help guide treatment of apathy, but they do not show any effect on curing or preventing Alzheimer's disease.
Study details
- Participants44
- Evidence strengthHigh
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International Psychogeriatrics) |
| Journal's citation record | 2 / 4 | International Psychogeriatrics: journal h-index 161 (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 | 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 44 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 9.5× 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 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Krista L. Lanctôt: h-index 84 (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 18 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41521126) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.inpsyc.2025.100181
- PubMed: 41521126
- Original source →
- Free full text: International Psychogeriatrics →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Sankhe, K., Ruthirakuhan, M. T., Andreazza, A. C., Brawman‐Mintzer, O., Craft, S., Herrmann, N., et al. (2026). Peripheral biomarkers associated with apathy and predicting response to methylphenidate: Secondary analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET2) study. International Psychogeriatrics. https://doi.org/10.1016/j.inpsyc.2025.100181
Vancouver
Sankhe K, Ruthirakuhan MT, Andreazza AC, Brawman‐Mintzer O, Craft S, Herrmann N, et al. Peripheral biomarkers associated with apathy and predicting response to methylphenidate: Secondary analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET2) study. International Psychogeriatrics. 2026. doi:10.1016/j.inpsyc.2025.100181. PMID: 41521126.
BibTeX
@article{sankhe2026-41521126,
author = {Sankhe, Krushnaa and Ruthirakuhan, Myuri T. and Andreazza, Ana C. and Brawman‐Mintzer, Olga and Craft, Suzanne and Herrmann, Nathan and Ismail, Zahinoor and Lerner, Alan J. and others},
title = {{Peripheral biomarkers associated with apathy and predicting response to methylphenidate: Secondary analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET2) study}},
journal = {International Psychogeriatrics},
year = {2026},
doi = {10.1016/j.inpsyc.2025.100181},
pmid = {41521126},
url = {https://doi.org/10.1016/j.inpsyc.2025.100181}
}
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