Evidence map›Paper›PMID 40396657›Full record

ArticleHuman brain mapping2025

Neurophysiological Progression in Alzheimer's Disease: Insights From Dynamic Causal Modelling of Longitudinal Magnetoencephalography.

Amirhossein Jafarian, Melek Karadag Assem, Ece Kocagoncu, Juliette H Lanskey, Haddy Fye, Rebecca Williams, Andrew J Quinn, Jemma Pitt, Vanessa Raymont, Stephen Lowe and 6 more

Abstract read
In one paragraph

Article in Human brain mapping, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

16 authors.

Amirhossein JafarianMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.ORCID 0000-0001-9547-7941
Melek Karadag AssemMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.
Ece KocagoncuMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.
Juliette H LanskeyMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.
Haddy FyeDepartment of Clinical Neurosciences and Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Rebecca WilliamsMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.
Andrew J QuinnOxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK.
Jemma PittDepartment of Psychiatry, University of Oxford, Oxford, UK.
Vanessa RaymontDepartment of Psychiatry, University of Oxford, Oxford, UK.
Stephen LoweLilly Centre for Clinical Pharmacology, Singapore.
Krish D SinghCardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.
Mark WoolrichOxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK.
Anna C NobreDepartment of Psychiatry, University of Oxford, Oxford, UK.
Richard N HensonMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.ORCID 0000-0002-0712-2639
Karl J FristonQueen Square, Institute of Neurology, University College London, London, UK.ORCID 0000-0001-7984-8909
James B RoweMRC Cognition and Brain Sciences, University of Cambridge, Cambridge, UK.ORCID 0000-0001-7216-8679

Funding

Alzheimers Research UK ARUK-PG2017B-19Medical Research Council MC_UU_00030/14Medical Research Council MR/T033371/1National Institute for Health Research Oxford Health Biomedical Research Centre NIHR203316NIHR Cambridge Biomedical Research Centre NIHR203312Wellcome Trust 220258
6 · The paper itself

Abstract

Neurodegenerative diseases, including Alzheimer's disease, are characterised by selective neuronal vulnerability with regional, laminar, cellular and neurotransmitter specificity. The regional losses of neurons and their synapses are associated with neurophysiological changes and cognitive decline. Hypotheses related to these mechanisms can be tested and compared by dynamic causal modelling (DCM) of human neuroimaging data, including magnetoencephalography (MEG). In this paper, we use DCM of cross-spectral densities to model changes between baseline and follow-up data in cortical regions of the default mode network, to characterise longitudinal changes in cortical microcircuits and their connectivity underlying resting-state MEG. Twenty-nine people with amyloid-positive mild cognitive impairment and Alzheimer's disease early dementia were studied at baseline and after an average interval of 16 months. To study longitudinal changes induced by Alzheimer's disease, we evaluate three complementary sets of DCM: (i) with regional specificity, of the contributions of neurons to measurements to accommodate regional variability in disease burden; (ii) with dual parameterisation of excitatory neurotransmission, motivated by preclinical and clinical evidence of distinct effects of disease on AMPA versus NMDA type glutamate receptors; and (iii) with constraints to test specific clinical hypothesis about the effects of disease-progression. Bayesian model selection at the group level confirmed evidence for regional specificity of the effects of Alzheimer's disease, with evidence for selective changes in NMDA neurotransmission, and progressive changes in connectivity within and between Precuneus and medial prefrontal cortex. Moreover, alterations in effective connectivity vary in accordance with individual differences in cognitive decline during follow-up. These applications of DCM enrich the mechanistic understanding of the pathophysiology of human Alzheimer's disease and inform experimental medicine studies of novel therapies. More generally, longitudinal DCM provides a potential platform for natural history and interventional studies of neurodegenerative and neuropsychiatric diseases, with selective neuronal vulnerability.

Indexed as

Alzheimer DiseaseCerebral CortexCognitive DysfunctionConnectomeDefault Mode NetworkMagnetoencephalographyNerve NetAgedAged, 80 and overDisease ProgressionFemaleHumansLongitudinal StudiesMaleMiddle AgedAlzheimer's diseasedynamic causal modellingmagnetoencephalographyparametric empirical Bayes

Identifiers

PMID40396657
PMCPMC12093352

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Registered trials

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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.