Evidence map›Paper›PMID 41668114›Full record

ArticleAlzheimer's research & therapy2026

Functional network phenotypes of mild behavioural impairment: cognitive effects moderated by amyloid.

Kok Pin Ng, Joanna Su Xian Chong, Firoza Lussier, Joseph Therriault, Nesrine Rahmouni, Melissa Savard, Jenna Stevenson, Tharick Pascoal, Serge Gauthier, Pedro Rosa-Neto and 1 more

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Kok Pin Ng *National Neuroscience Institute, Department of Neurology, Singapore, 308433, Singapore.
Joanna Su Xian Chong *Centre for Sleep and Cognition & Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117549, Singapore.
Firoza LussierDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Joseph TherriaultTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, Montreal Neurological Institute, Montreal, QC, H4H 1R3, Canada.
Nesrine RahmouniTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, Montreal Neurological Institute, Montreal, QC, H4H 1R3, Canada.
Melissa SavardTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, Montreal Neurological Institute, Montreal, QC, H4H 1R3, Canada.
Jenna StevensonTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, Montreal Neurological Institute, Montreal, QC, H4H 1R3, Canada.
Tharick PascoalDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Serge GauthierMcGill Research Center for Studies in Aging and Dementia Education Program, McGill University, Montreal, QC, H4H 1R3, Canada.
Pedro Rosa-Neto *Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, Montreal Neurological Institute, Montreal, QC, H4H 1R3, Canada.
Juan Helen Zhou *Centre for Sleep and Cognition & Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117549, Singapore. helen.zhou@nus.edu.sg.

Funding

A*STAR, Singapore RIE2020 AME Programmatic Fund No. A20G8b0102Brain Canada Foundation CFI Project 34874; 33397Canadian Consortium of Neurodegeneration and Aging (CCNA) MOP-11-51-31 -team 1Ministry of Education - Singapore MOE-T2EP40120-0007 and T2EP2-0223-0025, MOE-T2EP20220-0001National University of Singapore Yong Loo Lin School of Medicine Research Core FundingSingapore National Medical Research Council NMRC/OFLCG19May-0035, NMRC/CIRG/1485/2018, NMRC/CSA-SI/0007/2016, NMRC/MOH-00707-01, NMRC/CG/435 M009/2017-NUH/NUHS, CIRG21nov-0007, HLCA23Feb-0004 and OFIRG24Jul-0049The Alzheimer's Association NIRG-12-92090, NIRP-12-259245The Fonds de Recherche du Québec - Santé (FRQS) Chercheur Boursier, 2020-VICO-279314Weston Brain Institute, Canadian Institutes of Health Research (CIHR) MOP-11-51-31; RFN 152985, 159815, 162303
6 · The paper itself

Abstract

backgroundMild behavioural impairment (MBI) is a neurobehavioural syndrome that represents an at-risk state for incident cognitive decline. No study to date has systematically investigated whole-brain within- and between- network functional connectivity (FC) disruptions in MBI and their effects on cognitive performance in dementia-free individuals. Hence, we sought to evaluate the whole-brain functional network phenotypes associated with MBI and its subdomains, and their relationships with amyloid and tau pathology in predicting future cognition and function in dementia-free older adults.

methodsWe studied 203 dementia-free individuals aged between 55 and 90 years (77 males) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with baseline functional MRI, amyloid-β [18 F]AZD4694 and tau [18 F]MK6240 PET imaging, and longitudinal neuropsychological assessments up to 32 months. Multivariate associations between MBI-Checklist (MBI-C) subdomain scores and whole-brain FC matrices were examined using partial least squares correlation. We then assessed how these MBI-related network phenotypes were associated with baseline and longitudinal changes in global cognition (via Montreal Cognitive Assessment (MoCA) scores) and functional performance (via clinical dementia rating (CDR) sum of boxes), and whether they interacted with baseline Alzheimer’s disease pathology (global amyloid uptake and tau temporal meta-region-of-interest uptake via PET) to influence future outcomes using linear regression models.

resultsWe identified an MBI-related functional network phenotype characterized by greater MBI severity and widespread dysfunctions particularly in higher-order networks. Greater expression of this phenotype was associated with poorer baseline global cognition, as well as greater functional impairment at baseline and over time. Further, baseline global amyloid uptake, but not temporal tau uptake, moderated the effects of baseline MBI-related FC disruptions on longitudinal global cognition changes in dementia-free older adults. Specifically, individuals with higher amyloid burden and greater MBI-related FC disruptions showed accelerated cognitive decline over time. In contrast, the MBI-C total score did not show independent or interactive effects with amyloid and tau burden on longitudinal cognitive and functional outcomes.

conclusionsOur findings demonstrated a global MBI-related functional network phenotype in dementia-free individuals that was associated with impaired cognition and function. Moreover, this phenotype interacts with amyloid burden to accelerate cognitive decline, underscoring its relevance in preclinical Alzheimer’s disease.

Indexed as

Amyloid beta-PeptidesBrainCognitionCognitive DysfunctionAgedAged, 80 and overFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsPhenotypePositron-Emission Tomographytau ProteinsAmyloid beta-Peptidestau ProteinsAmyloidBrain functional networksCognitive declineMild behavioural impairment

Identifiers

PMID41668114
PMCPMC12990541

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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.