{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:34:13Z","timestamp":1789486453853,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) is characterized by amyloid deposition, brain hypometabolism, gray matter atrophy and cognitive decline, yet their causal interactions are poorly defined. This multimodal PET\/MRI study explored regional gray matter volume (GMV) loss and glucose hypometabolism in AD patients, and clarified their correlations with distinct cognitive deficits alongside mediating pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      134 probable dementia patients were split into AD and non-AD dementia cohorts based on\n                      <jats:sup>18<\/jats:sup>\n                      F-AV45 PET amyloid-\u03b2 (A\u03b2) load, all receiving structural MRI,\n                      <jats:sup>18<\/jats:sup>\n                      F-FDG and\n                      <jats:sup>18<\/jats:sup>\n                      F-AV45 PET scans. We compared intergroup GMV and metabolic discrepancies, analyzed imaging-cognition correlations adjusted for clinical and demographic confounders, and implemented mediation models to test whether GMV bridges cerebral metabolism and cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AD patients exhibited prominent regional GMV shrinkage and FDG hypometabolism in vulnerable brain regions relative to non-AD dementia subjects. Covariate-adjusted analyses linked both imaging biomarkers to domain-specific cognitive performance. Primary mediation analyses showed that regional GMV significantly mediated the associations between FDG metabolism and visuospatial, executive, and language function, accounting for 40.36, 35.60, and 49.99% of the total effects, respectively. Reverse mediation models identified only a weak indirect effect of right superior temporal gyrus metabolism on the association between right inferior parietal lobule GMV and visuospatial ability, accounting for 13.26% of the total effect. Moreover, after multiple-imputation sensitivity analyses, most indirect effects became unstable or nonsignificant, suggesting that the FDG metabolism\u2013cognition association is predominantly direct, with limited evidence for GMV mediation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integrated PET\/MRI revealed AD-related patterns of regional atrophy and hypometabolism. Overall, the association between cerebral metabolic dysfunction and cognitive impairment appeared to be predominantly direct, with limited evidence supporting a mediating role of regional GMV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1919778","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:06:36Z","timestamp":1789477596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gray matter atrophy mediates the association between cerebral hypometabolism and cognitive impairment in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Shiqi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbo","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"The Center for Gerontology and Geriatrics, Dalian Friendship Hospital","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.maturitas.2020.05.018","article-title":"The World Health Organization (WHO) approach to healthy ageing","volume":"139","author":"Rudnicka","year":"2020","journal-title":"Maturitas"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1093\/brain\/awp062","article-title":"Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease","volume":"132","author":"Jack","year":"2009","journal-title":"Brain"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"4704","DOI":"10.1002\/hbm.25151","article-title":"Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease","volume":"41","author":"Xie","year":"2020","journal-title":"Hum Brain Mapp"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jpsychires.2023.07.026","article-title":"Neuroticism and white matter hyperintensities","volume":"165","author":"Terracciano","year":"2023","journal-title":"J Psychiatr Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1111\/j.1460-9568.2011.07745.x","article-title":"Structure and function of medial temporal and posteromedial cortices in early Alzheimer's disease","volume":"34","author":"Miettinen","year":"2011","journal-title":"Eur J Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1212\/WNL.0b013e31828970c2","article-title":"Cognitive reserve associated with FDG-PET in preclinical Alzheimer disease","volume":"80","author":"Ewers","year":"2013","journal-title":"Neurology"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3233\/JAD-215724","article-title":"A multi-dimensional comparison of Alzheimer's disease neurodegenerative biomarkers","volume":"87","author":"Liu","year":"2022","journal-title":"J Alzheimer's Dis"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1093\/brain\/awv278","article-title":"Regional brain hypometabolism is unrelated to regional amyloid plaque burden","volume":"138","author":"Altmann","year":"2015","journal-title":"Brain"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e14418","DOI":"10.1111\/cns.14418","article-title":"The value of FDG combined with PiB PET in the diagnosis of patients with cognitive impairment in a memory clinic","volume":"30","author":"Liu","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S72","DOI":"10.1016\/j.jalz.2012.10.007","article-title":"Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer's disease dementia, mild cognitive impairment, and normal aging","volume":"9","author":"Johnson","year":"2013","journal-title":"Alzheimers Dement"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/mp.2011.52","article-title":"ApoE and Alzheimer disease: a major gene with semi-dominant inheritance","volume":"16","author":"Genin","year":"2011","journal-title":"Mol Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"10256","DOI":"10.1073\/pnas.1001412107","article-title":"Apolipoprotein E (ApoE) genotype has dissociable effects on memory and attentional-executive network function in Alzheimer's disease","volume":"107","author":"Wolk","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/S1474-4422(10)70306-9","article-title":"Early-onset versus late-onset Alzheimer's disease: the case of the missing ApoE \u025b4 allele","volume":"10","author":"van der Flier","year":"2011","journal-title":"Lancet Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13195-018-0403-x","article-title":"Greater tau load and reduced cortical thickness in ApoE \u03b54-negative Alzheimer's disease: a cohort study","volume":"10","author":"Mattsson","year":"2018","journal-title":"Alzheimer's Res Ther"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"101795","DOI":"10.1016\/j.nicl.2019.101795","article-title":"The effect of ApoE \u03b54 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study","volume":"22","author":"Paranjpe","year":"2019","journal-title":"Neuroimage Clin"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/ene.15656","article-title":"Effect of APOE \u03b54 genotype on amyloid-\u03b2, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment","volume":"30","author":"Li","year":"2023","journal-title":"Eur J Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.neuroscience.2005.12.061","article-title":"The multi-component model of working memory: explorations in experimental cognitive psychology","volume":"139","author":"Repovs","year":"2006","journal-title":"Neuroscience"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1007\/s00415-018-8762-6","article-title":"Primary progressive aphasia: a clinical approach","volume":"265","author":"Marshall","year":"2018","journal-title":"J Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1684\/pnv.2019.0815","article-title":"Les troubles de la perception visuelle dans la maladie d\u2019Alzheimer [Visual perceptual disorders in Alzheimer's disease]","volume":"17","author":"Lenoir","year":"2019","journal-title":"Geriatr Psychol Neuropsychiatr Vieil"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3827","DOI":"10.1002\/cne.23126","article-title":"Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters","volume":"520","author":"Sundvik","year":"2012","journal-title":"J Comp Neurol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1093\/brain\/121.4.611","article-title":"The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization","volume":"121","author":"Desgranges","year":"1998","journal-title":"Brain"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"7228","DOI":"10.18632\/aging.202580","article-title":"Evaluating the association between brain atrophy, hypometabolism, and cognitive decline in Alzheimer's disease: a PET\/MRI study","volume":"13","author":"Chen","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/S1474-4422(07)70178-3","article-title":"Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria","volume":"6","author":"Dubois","year":"2007","journal-title":"Lancet Neurol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1177\/13872877261452181","article-title":"Uncovering the causal link between cerebral glucose metabolism and cognitive function in Alzheimer's disease","volume":"112","author":"Trist\u00e3o-Pereira","year":"2026","journal-title":"J Alzheimer's Dis"},{"key":"ref27","volume-title":"Diagnostic and Statistical Manual of mental Disorders, text Revision","year":"2000"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1111\/jgs.12541","article-title":"Criterion and convergent validity of the Montreal cognitive assessment with screening and standardized neuropsychological testing","volume":"61","author":"Lam","year":"2013","journal-title":"J Am Geriatr Soc"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1001\/jama.1963.03060120024016","article-title":"Studies of illness in the aged. the index of ADL: a standardized measure of biological and psychosocial function","volume":"185","author":"Katz","year":"1963","journal-title":"JAMA"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1959","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"NeuroImage"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/s0896-6273(02)00569-x","article-title":"Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain","volume":"33","author":"Fischl","year":"2002","journal-title":"Neuron"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1006\/nimg.2001.0845","article-title":"Spatial normalization of brain images with focal lesions using cost function masking","volume":"14","author":"Brett","year":"2001","journal-title":"NeuroImage"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.neuroimage.2013.12.021","article-title":"Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data","volume":"92","author":"Greve","year":"2014","journal-title":"NeuroImage"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9261","DOI":"10.1038\/s41598-020-65957-3","article-title":"Selection of the optimal intensity normalization region for FDG-PET studies of normal aging and Alzheimer's disease","volume":"10","author":"Nugent","year":"2020","journal-title":"Sci Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S1474-4422(12)70142-4","article-title":"Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-\u03b2 plaques: a prospective cohort study","volume":"11","author":"Clark","year":"2012","journal-title":"Lancet Neurol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer's disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1440.011","article-title":"The brain's default network: anatomy, function, and relevance to disease","volume":"1124","author":"Buckner","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/ana.410420114","article-title":"Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease","volume":"42","author":"Minoshima","year":"1997","journal-title":"Ann Neurol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"4637","DOI":"10.1073\/pnas.0308627101","article-title":"Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI","volume":"101","author":"Greicius","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"7709","DOI":"10.1523\/JNEUROSCI.2177-05.2005","article-title":"Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory","volume":"25","author":"Buckner","year":"2005","journal-title":"J Neurosci"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12017-009-8109-7","article-title":"Functional alterations in memory networks in early Alzheimer's disease","volume":"12","author":"Sperling","year":"2010","journal-title":"NeuroMolecular Med"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/cercor\/bhu226","article-title":"A predominantly visual subdivision of the right Temporo-parietal junction (vTPJ)","volume":"26","author":"Horiguchi","year":"2016","journal-title":"Cereb Cortex"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1080\/13554791003730600","article-title":"Visual spatial cognition in neurodegenerative disease","volume":"16","author":"Possin","year":"2010","journal-title":"Neurocase"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"121229","DOI":"10.1016\/j.neuroimage.2025.121229","article-title":"Linking visual-frontoparietal network neural dynamics to spontaneous cognitive processing","volume":"312","author":"Li","year":"2025","journal-title":"NeuroImage"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1002\/hbm.24701","article-title":"Characterization of a temporoparietal junction subtype of Alzheimer's disease","volume":"40","author":"Meyer","year":"2019","journal-title":"Hum Brain Mapp"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3389\/fnhum.2011.00059","article-title":"Recency effects in the inferior parietal lobe during verbal recognition memory","volume":"5","author":"Buchsbaum","year":"2011","journal-title":"Front Hum Neurosci"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cortex.2017.10.003","article-title":"Role of the right inferior parietal cortex in auditory selective attention: an rTMS study","volume":"99","author":"Bareham","year":"2018","journal-title":"Cortex"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3390\/biom1106823","article-title":"Understanding emotions: origins and roles of the amygdala","volume":"11","author":"\u0160imi\u0107","year":"2021","journal-title":"Biomolecules"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/B978-0-12-821375-9.00002-5","article-title":"Amygdala connectivity and aggression","volume":"197","author":"Tonnaer","year":"2023","journal-title":"Handb Clin Neurol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.neuroscience.2025.06.034","article-title":"Distinct connectivity patterns in clusters of inferior parietal cortex: from a cognitive control hub to modulating cortical areas","volume":"580","author":"Tabassi Mofrad","year":"2025","journal-title":"Neuroscience"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.pscychresns.2011.06.014","article-title":"Amygdala atrophy is prominent in early Alzheimer's disease and relates to symptom severity","volume":"194","author":"Poulin","year":"2011","journal-title":"Psychiatry Res"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1212\/01.wnl.0000144273.82654.96","article-title":"Atypical language cortex in the left temporal lobe: relationship to bilateral language","volume":"63","author":"Jabbour","year":"2004","journal-title":"Neurology"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/hbm.20493","article-title":"Neural substrates of phonological and lexicosemantic representations in Alzheimer's disease","volume":"30","author":"Peters","year":"2009","journal-title":"Hum Brain Mapp"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.neurobiolaging.2010.05.020","article-title":"Alzheimer's pathology in primary progressive aphasia","volume":"33","author":"Rohrer","year":"2012","journal-title":"Neurobiol Aging"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1177\/0271678X0102101001","article-title":"An energy budget for signaling in the grey matter of the brain","volume":"21","author":"Attwell","year":"2001","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.009","article-title":"A cellular perspective on brain energy metabolism and functional imaging","volume":"86","author":"Magistretti","year":"2015","journal-title":"Neuron"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/ana.410300603","article-title":"Physical basis of cognitive alterations in Alzheimer\u2019s disease: synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry","year":"1991","journal-title":"Ann Neurol"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/nn.2588","article-title":"Amyloid-\u03b2-induced neuronal dysfunction in Alzheimer\u2019s disease: from synapses toward neural networks","volume":"13","author":"Palop","year":"2010","journal-title":"Nat Neurosci"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer's disease","volume":"19","author":"Singh","year":"2022","journal-title":"J Neuroinflammation"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.neuron.2013.10.008","article-title":"The pathobiology of vascular dementia","volume":"80","author":"Iadecola","year":"2013","journal-title":"Neuron"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nrn.2017.48","article-title":"Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease","volume":"18","author":"Kisler","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neuron.2009.03.031","article-title":"Neurodegenerative diseases target large-scale human brain networks","volume":"62","author":"Seeley","year":"2009","journal-title":"Neuron"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.neuron.2012.01.042","article-title":"A network diffusion model of disease progression in dementia","volume":"73","author":"Raj","year":"2012","journal-title":"Neuron"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1919778\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:06:38Z","timestamp":1789477598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1919778\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":71,"alternative-id":["10.3389\/fneur.2026.1919778"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1919778","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1919778"}}