Evidence map›Paper›PMID 41980907›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2026

A phase 2, randomized, multicenter, double-blind, placebo-controlled trial of S-adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer's disease.

Sarah Holper, Kevin J Barnham, Leonid Churilov, Paul Yates, Amy Brodtmann, Sally Johns, Qia-Xin Li, Oneil Bhalala, Kai Sin Chin, Paula Loveland and 4 more

Abstract readMulticenter StudyRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

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

14 authors.

Sarah HolperDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0003-4257-964X
Kevin J BarnhamNational Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Leonid ChurilovDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Paul YatesDepartment of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
Amy BrodtmannDepartment of Neurology, Eastern Health, Monash University, Box Hill, Victoria, Australia.
Sally JohnsDepartment of Geriatric Medicine, Modbury Hospital, Northern Adelaide Local Health Network, Adelaide, South Australia, Australia.
Qia-Xin LiNational Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Oneil BhalalaDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Kai Sin ChinDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Paula LovelandDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Jenny Jia YuDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Colin L MastersNational Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Rosie WatsonDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Nawaf YassiDepartment of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Funding

Alzheimer's AssociationNational Health and Medical Research Council
6 · The paper itself

Abstract

introductionS-adenosyl methionine (SAMe) is a pivotal metabolite in multiple neuronal pathways, including tau dephosphorylation. Reduced SAMe availability has been reported in the Alzheimer's disease (AD) brain, prompting interest in supplementation as a potential therapeutic strategy.

methodsThis multicenter, randomized, double-blind, placebo-controlled phase 2 study recruited people (n = 63) with a clinical AD diagnosis. Participants received 180 days of SAMe (400 mg daily) or placebo. Primary outcome was change in plasma phosphorylated tau (p-tau)217 concentration. Secondary endpoints included safety, tolerability, and cognitive outcomes.

resultsMean percentage change in plasma p-tau217 in the SAMe group was an increase of 53.22 (standard deviation [SD] 159.19) compared to 25.34 (SD 94.83) in the placebo group (standardized mean difference 37.58, 95% confidence interval -32.61, 107.76; p = 0.288). No significant differences were observed in safety or other secondary endpoints. DISCUSSION: SAMe did not demonstrate disease-modifying efficacy at the dose and duration studied; however it was safe and well tolerated.

trial registrationACTRN12620000506998. Registered on the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au).

Indexed as

Alzheimer DiseaseCognitive DysfunctionS-AdenosylmethionineAgedAged, 80 and overDouble-Blind MethodFemaleHumansMaletau ProteinsTreatment OutcomeS-Adenosylmethioninetau ProteinsAlzheimer's diseasebiomarkerclinical trialS‐adenosyl methioninetau

Identifiers

PMID41980907
PMCPMC13079069

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.