Differential associations of tau extent and load with brain metabolic and cognitive dysfunction in Alzheimer's disease
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Le résumé fourni par la source
Background Reduced [ 18 F]Fluorodeoxyglucose ([ 18 F]FDG)-PET uptake is a core imaging feature of Alzheimer's disease (AD). While tau load correlates with this metabolic signature, it remains unclear whether the spatial extent of tauopathy (SEOT) more accurately explains brain glucose hypometabolic patterns. Here, we compared SEOT versus tau load to determine their ability to predict brain hypometabolic signatures in AD. Methods We performed a cross-sectional study of amyloid-β positive participants from ADNI (n = 150) and an atypical AD subset from the McGill University Research Centre for Studies in Ageing (MCSA; n=44). Participants underwent [ 18 F]AV1451 or [ 18 F]MK6240 tau-PET and [ 18 F]FDG-PET. Tau load was indexed with regional SUVR, and SEOT with the proportion of abnormal voxels. Linear regressions related temporal and whole-cortex tau-PET load or SEOT to [ 18 F]FDG-PET. We also compared the accuracy of tau-PET metrics for identifying AD-like hypometabolism. Spearman correlations assessed SEOT/tau load-FDG associations at regional and network levels. Partial Least Squares (PLS) regression investigated whether distributed tau load and SEOT predicted [ 18 F]FDG-PET signatures. Structural equation modelling and hierarchical linear models assessed associations between tau metrics and cognition dependent and independent of [ 18 F]FDG-PET. Findings Whole-cortex SEOT best predicted decreased signal in the [ 18 F]FDG-PET AD-meta-ROI. SEOT also performed better in classifying AD-related brain hypometabolism. Across regions and networks, SEOT performed similarly or better than tau load in predicting metabolic dysfunction. Voxelwise analyses suggested complementary predictive value of SEOT and tau load, each capturing slightly distinct spatial associations with [ 18 F]FDG-PET. PLS demonstrated partially non-redundant contributions from tau load and SEOT. Cortical SEOT showed the strongest predictive value for cognition. Interpretation SEOT provides complementary, independent, and often stronger predictive value than tau load for brain metabolism, particularly for network-level dysfunction. SEOT may improve diagnostic characterisation and prediction of cognitive impairment beyond [ 18 F]FDG-PET. Funding TRIAD is supported by the Weston Brain Institute, Canadian Institutes of Health Research, Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, the Fonds de Recherche du Québec – Santé, and the Colin J Adair Charitable Foundation. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and the Canadian Institutes of Health Research.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Differential associations of tau extent and load with brain metabolic and cognitive dysfunction in Alzheimer's disease
- Date Crossref
- 01/09/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Montreal Neurological Institute and Hospital pays non établi dans la noticeÉtablissement de santé
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McGill University Research Centre for Studies in Aging Translational Neuroimaging Laboratory pays non établi dans la noticeStructure de recherche
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Universität Hamburg pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Hamburg-Eppendorf pays non établi dans la noticeÉtablissement de santé
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Universidade Federal do Rio Grande do Sul Graduate Program of Biological Sciences: Biochemistry pays non établi dans la noticeUniversité ou école supérieure
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University of Gothenburg Department of Psychiatry and Neurochemistry pays non établi dans la noticeUniversité ou école supérieure
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Instituto do Cérebro pays non établi dans la noticeOrganisation à but non lucratif
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Centre Hospitalier de l’Université de Montréal Douglas Hospital Research Centre - Centre intégré universitaire de santé et services sociaux de l'Ouest-de-l'Île-de-Montréal pays non établi dans la noticeÉtablissement de santé
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Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-Montréal pays non établi dans la noticeÉtablissement de santé
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University of Pittsburgh pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Department of Psychiatry pays non établi dans la noticeUniversité ou école supérieure
Montreal Neurological Institute and Hospital, Translational Neuroimaging Laboratory — McGill University Research Centre for Studies in Aging et Universität Hamburg, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.