Evidence map›Paper›PMID 41521126›Full record

ArticleInternational psychogeriatrics2026

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 Ruthirakuhan, Ana C Andreazza, Olga Brawman-Mintzer, Suzanne Craft, Nathan Herrmann, Zahinoor Ismail, Alan J Lerner, Allan I Levey, Jacobo Mintzer and 8 more

Registry-linked trialAbstract read
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In one paragraph

Article in International psychogeriatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02346201 (Apathy in Dementia Methylphenidate Trial 2), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02346201 phase3completednot on this map

Apathy in Dementia Methylphenidate Trial 2

TypeinterventionalSponsorJohns Hopkins Bloomberg School of Public HealthRan2016 to 2020Enrolled200ConditionsApathy, Alzheimer's DiseaseArmsMethylphenidate, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Krushnaa SankheSunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Myuri RuthirakuhanSunnybrook Research Institute, Toronto, ON, Canada.
Ana C AndreazzaDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Olga Brawman-MintzerRalph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, SC, USA.
Suzanne CraftWake Forest University, Winston-Salem, NC, USA.
Nathan HerrmannSunnybrook Research Institute, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Zahinoor IsmailDepartment of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Alan J LernerDepartment of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Allan I LeveyGoizueta Brain Health Institute, Emory University, Atlanta, GA, USA.
Jacobo MintzerRalph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, SC, USA.
Prasad R PadalaCentral Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jamie PerinJohns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
Anton P PorsteinssonDepartment of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Paul B RosenbergJohns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA.
David ShadeJohns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
Shankar TumatiDepartment of Psychiatry, Rutgers University, Newark, NJ, USA.
Christopher H van DyckYale School of Medicine, New Haven, CT, USA.
Krista L LanctôtSunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: krista.lanctot@sunnybrook.ca.

Funding

Apathy in Alzheimer's Disease Methyphenidate Trial II (ADMET II)R01AG046543 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HERRMANN, NATHAN, LANCTOT, KRISTA L. · 2014 to 2018
$8.1M
NIA NIH HHS R01 AG046543
6 · The paper itself

Abstract

backgroundIn Apathy in Dementia Methylphenidate Trial 2 (ADMET2), apathy in Alzheimer's disease improved with methylphenidate (MPH) in a randomized, placebo-controlled trial, though response varied. Here we evaluated serum biomarkers for their association with apathy and with treatment response.

methodsAll ADMET2 participants with available blood samples were included. Markers of inflammation [interleukin (IL)-6, IL-10, Tumor Necrosis Factor (TNF)], oxidative stress [lipid hydroperoxide (LPH), 4-hydroxynonenal (4-HNE), 8-isoprostane (8-ISO)] and neuronal injury [neurofilament light (NfL), S100B] were assessed and values log-transformed. Neuropsychiatric Inventory-apathy (NPI-A) measured apathy. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for feature selection of baseline markers predicting NPI-A at Month-6 (M6). Univariate analyses examined individual biomarker effects and multivariable models evaluated their combined effects. Treatment interactions, baseline and change in biomarker levels in treatment responders (≥4 change in NPI-A) and remitters (M6 NPI-A=0) were explored.

resultsIn 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].

conclusionsInflammatory 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.

Indexed as

Alzheimer’s diseaseApathyMethylphenidateNeurofilament lightS100BTumor necrosis factor

Identifiers

PMID41521126
PMCPMC12959483

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.