Resting-state functional and spectral alterations underlying cognitive decline in biomarker-confirmed Alzheimer's disease: A systematic review.

Soraya Alfonsín, Brenda Chino, Jaisalmer de Frutos Lucas, María Luisa Delgado-Losada, Natalia Ojeda, Fernando Maestú

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Article in NeuroImage. Clinical, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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Soraya AlfonsínDepartment of Experimental Psychology, Faculty of Psychology. Complutense University of Madrid (UCM), Av. Complutense, s/n, Moncloa - Aravaca, 28040 Madrid, Spain; Center for Cognitive and Computational Neuroscience. Complutense University of Madrid (UCM), Madrid, Spain.

Brenda ChinoDepartment of Psychology, Faculty of Health Sciences, University of Deusto, Bilbao, Bizkaia, Spain. Electronic address: brendanadia.chino@deusto.es.

Jaisalmer de Frutos LucasSchool of Social Sciences and Communications, Universidad Europea, C/ Tajo, s/n. Urb. El Bosque 28670 Villaviciosa de Odon, Madrid, Spain.

María Luisa Delgado-LosadaDepartment of Experimental Psychology, Faculty of Psychology. Complutense University of Madrid (UCM), Av. Complutense, s/n, Moncloa - Aravaca, 28040 Madrid, Spain; Ageing, Disability and Society Research Group (ENDISSCO). Complutense University of Madrid (UCM), Av. Complutense, s/n, Moncloa - Aravaca, 28040 Madrid, Spain.

Natalia OjedaDepartment of Psychology, Faculty of Health Sciences, University of Deusto, Bilbao, Bizkaia, Spain.

Fernando MaestúDepartment of Experimental Psychology, Faculty of Psychology. Complutense University of Madrid (UCM), Av. Complutense, s/n, Moncloa - Aravaca, 28040 Madrid, Spain; Center for Cognitive and Computational Neuroscience. Complutense University of Madrid (UCM), Madrid, Spain; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain.

Funding

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6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with synaptic and large-scale network dysfunction. Resting-state alterations may provide functional correlates of AD pathology, but associations among intrinsic brain activity, biomarkers, and domain-specific cognition have not been systematically integrated across spectral and connectivity frameworks. We systematically reviewed PubMed, Scopus, and Web of Science through May 2025 (PROSPERO CRD42024575913). Thirty studies (N = 5898) examining resting-state EEG, MEG, or fMRI, AD biomarkers, and cognition were synthesized following SWiM guidance. Across studies, resting-state alterations showed converging associations with amyloid and tau measures from CSF, PET, and plasma. Five of six electrophysiological studies reported increased delta/theta activity and three of six reduced alpha/beta activity, supporting neural slowing. Greater low-frequency activity was generally associated with poorer global cognition and episodic memory, whereas reduced higher-frequency activity was linked to poorer attention and processing speed. Among 21 connectivity studies, 10 reported hyperconnectivity and 13 hypoconnectivity, with non-mutually exclusive categories. Hyperconnectivity, particularly within medial and anterior temporal circuits, was more frequent in earlier-stage groups and showed heterogeneous cognitive associations, including poorer and better-preserved performance. Broader hypoconnectivity across posterior default mode, medial temporal-posterior medial, and frontoparietal networks was more prominent in later-stage groups and more consistently associated with poorer global cognition, episodic memory, and executive function. These findings support spectral slowing and stage-related network reorganization as functional correlates of cognitive impairment in biomarker-characterized AD. However, 25 of 30 studies were cross-sectional; therefore, these connectivity patterns should not be interpreted as a demonstrated within-person trajectory.

Indexed as

Alzheimer's diseaseAmyloid and tau biomarkersCognitionFunctional connectivityResting-state brain activity

Identifiers

PMID42810101

DOI10.1016/j.nicl.2026.104070

PMCPMC13654559

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