{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:51:48Z","timestamp":1786121508706,"version":"build-2736575974"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"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. Aging Neurosci."],"abstract":"<jats:p>Delirium Superimposed on Dementia (DSD) is a common neuropsychiatric disorder in hospitalized elderly populations with poor prognosis, which can accelerate cognitive decline and increase mortality. Despite its clinical significance, there is a lack of effective therapeutic methods in clinical practice. Mitochondrial dysfunction, characterized by impaired energy metabolism, excessive reactive oxygen species (ROS) production and neuroinflammation activation, has been suggested as a potentially critical pathogenic link in DSD. As an emerging organelle-based therapy, mitochondrial transplantation (MTT) restores cellular energy homeostasis and mitigates oxidative stress by delivering functional mitochondria into damaged cells, thus holding promising potential as a future strategy for DSD treatment. This review systematically summarizes the hypothesized pathological role of mitochondrial dysfunction in DSD and the technical system of MTT, including mitochondrial isolation, purification, preservation and delivery strategies. We further elaborate on the plausible neuroprotective mechanisms of MTT and its preclinical evidence in neurodegenerative disease models relevant to, but distinct from, DSD. Additionally, we comprehensively analyze the technical, immunological and clinical challenges of MTT in DSD treatment, and propose targeted solutions and future research directions. This review constructs a theoretical framework for the hypothetical translation of MTT from basic research to clinical application in DSD, and provides novel insights for the development of future etiological therapies for this devastating disorder.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1885815","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:27:42Z","timestamp":1786080462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial transplantation for delirium superimposed on dementia: from pathogenic mechanisms to clinical translation challenges"],"prefix":"10.3389","volume":"18","author":[{"given":"Weiwei","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Geriatric Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"He","sequence":"additional","affiliation":[{"name":"Department of Geriatric Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Geriatric Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"20487","DOI":"10.1021\/acsami.4c18415","article-title":"Development of a microfluidic system for mitochondrial extraction, purification, and analysis","volume":"17","author":"Ajmal","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.11.548594","article-title":"Purification of functional mouse skeletal muscle mitochondria using Percoll density gradient centrifugation","volume":"11","author":"Anunciado-Koza","year":"2023","journal-title":"bioRxiv"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood\u2013brain barrier","volume":"468","author":"Armulik","year":"2010","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e70329","DOI":"10.1002\/brb3.70329","article-title":"Effects of repetitive transcranial magnetic stimulation on tumor necrosis factor alpha in neuropsychological disorders: A systematic review and Meta-analysis","volume":"15","author":"Asadizeidabadi","year":"2025","journal-title":"Brain Behav."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"132227","DOI":"10.1016\/j.ijcard.2024.132227","article-title":"Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease","volume":"410","author":"Baharvand","year":"2024","journal-title":"Int. J. Cardiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"110106","DOI":"10.1016\/j.intimp.2023.110106","article-title":"Human umbilical cord-derived mesenchymal stem cells-harvested mitochondrial transplantation improved motor function in TBI models through rescuing neuronal cells from apoptosis and alleviating astrogliosis and microglia activation","volume":"118","author":"Bamshad","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.2174\/1570159X20666221012142247","article-title":"Microneedles: a versatile drug delivery carrier for phytobioactivecompounds as a therapeutic modulator for targeting mitochondrialdysfunction in the management of neurodegenerative diseases","volume":"22","author":"Bandiwadekar","year":"2024","journal-title":"Curr Neuropharmacol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e086909","DOI":"10.1002\/alz.086909","article-title":"Mitochondrial replenishment as a treatment for Alzheimer\u2019s disease","volume":"20","author":"Baudo","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","article-title":"Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation","volume":"14","author":"B\u00e9langer","year":"2011","journal-title":"Cell Metab."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.nbd.2015.10.011","article-title":"Mitochondrial fusion\/fission dynamics in neurodegeneration and neuronal plasticity","volume":"90","author":"Bertholet","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jare.2021.07.001","article-title":"CRISPR\/Cas9 gene editing: new hope for Alzheimer\u2019s disease therapeutics","volume":"40","author":"Bhardwaj","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13287-024-03771-8","article-title":"Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states","volume":"15","author":"Bodenstein","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1007\/s10072-021-05339-3","article-title":"Why is delirium more frequent in the elderly?","volume":"42","author":"Bugiani","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e70398","DOI":"10.1002\/dad2.70398","article-title":"The prevalence and incidence of delirium superimposed on dementia in community settings: A systematic review and meta-analysis","volume":"18","author":"Burnand","year":"2026","journal-title":"Alz Dem Diag Ass & Dis Mo"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"8922","DOI":"10.3390\/ijms25168922","article-title":"Metabolic reprogramming of astrocytes in pathological conditions: implications for neurodegenerative diseases","volume":"25","author":"Cal\u00ec","year":"2024","journal-title":"IJMS"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12987-019-0145-6","article-title":"An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons","volume":"16","author":"Canfield","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"113104","DOI":"10.1016\/j.intimp.2024.113104","article-title":"A promising therapeutic: exosome-mediated mitochondrial transplantation","volume":"142","author":"Cao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41419-024-07005-w","article-title":"Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes","volume":"15","author":"Capobianco","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1016\/j.healun.2025.07.002","article-title":"Revitalizing donor organs: the potential of mitochondrial transplantation in heart and lung transplantation","volume":"44","author":"Celik","year":"2025","journal-title":"J. Heart Lung Transplant."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.trsl.2015.12.003","article-title":"Allogeneic\/xenogeneic transplantation of peptide-labeled mitochondria in Parkinson\u2019s disease: restoration of mitochondria functions and attenuation of 6-hydroxydopamine\u2013induced neurotoxicity","volume":"170","author":"Chang","year":"2016","journal-title":"Transl. Res."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"7260305","DOI":"10.1155\/2022\/7260305","article-title":"The combination of Rhodosin and MMF prolongs cardiac allograft survival by inhibiting DC maturation by promoting mitochondrial fusion","volume":"2022","author":"Che","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1346441","DOI":"10.3389\/fendo.2023.1346441","article-title":"Mitochondrial transfer\u2014a novel promising approach for the treatment of metabolic diseases","volume":"14","author":"Chen","year":"2024","journal-title":"Front. Endocrinol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.freeradbiomed.2023.07.034","article-title":"Mitochondrial transplantation rescues neuronal cells from ferroptosis","volume":"208","author":"Chen","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1186\/s12967-022-03693-0","article-title":"Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease","volume":"20","author":"Chen","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1016\/j.bbadis.2018.06.012","article-title":"Mitochondrial therapy promotes regeneration of injured hippocampal neurons","volume":"1864","author":"Chien","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.healun.2023.01.002","article-title":"Cloer mitochondrial transplant after ischemia reperfusion promotes cellular salvage and improves lung function during ex-vivo lung perfusion","volume":"42","author":"Cloer","year":"2023","journal-title":"J. Heart Lung Transplant."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1186\/s12967-024-05627-4","article-title":"Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cells","volume":"22","author":"Court","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12951-025-03997-5","article-title":"RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2\/PI3K\/Akt pathway in Parkinson\u2019s disease mice","volume":"24","author":"Ding","year":"2026","journal-title":"J. Nanobiotechnol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e00317","DOI":"10.1002\/prp2.317","article-title":"Clinical trial allocation in multinational pharmaceutical companies \u2013 a qualitative study on influential factors","volume":"5","author":"Dombernowsky","year":"2017","journal-title":"Pharmacol. Res Perspec"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1007\/s00702-019-01980-7","article-title":"Management of delirium in Parkinson\u2019s disease","volume":"126","author":"Ebersbach","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e00355","DOI":"10.1016\/j.neurot.2024.e00355","article-title":"Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson\u2019s disease","volume":"21","author":"Eo","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/S1474-4422(15)00101-5","article-title":"The interface between delirium and dementia in elderly adults","volume":"14","author":"Fong","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s41582-022-00698-7","article-title":"The inter-relationship between delirium and dementia: the importance of delirium prevention","volume":"18","author":"Fong","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/br.2025.1966","article-title":"Research developments in the neurovascular unit and the blood-brain barrier (review)","volume":"22","author":"Gong","year":"2025","journal-title":"Biomed Rep."},{"key":"ref35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-0716-4414-0_17","volume-title":"T Cell Activation","author":"Gubert","year":"2025"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"801","DOI":"10.33549\/physiolres.935313","article-title":"POLG p.A962T mutation leads to neuronal mitochondrial dysfunction that is restored after mitochondrial transplantation","volume":"73","author":"Hu","year":"2024","journal-title":"Physiol. Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s12974-023-02794-x","article-title":"\u03b2-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium","volume":"20","author":"Hua","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jconrel.2023.12.054","article-title":"Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases","volume":"366","author":"Huang","year":"2024","journal-title":"J. Control. Release"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e326982","DOI":"10.1161\/CIRCRESAHA.125.326982","article-title":"Mitochondrial transfer to endothelial cells: mechanisms, evidence, and therapeutic potential","volume":"138","author":"Im","year":"2026","journal-title":"Circ. Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1093\/stmcls\/sxad028","article-title":"Neuroprotective effects of genome-edited human iPS cell-derived neural stem\/progenitor cells on traumatic brain injury","volume":"41","author":"Imai","year":"2023","journal-title":"Stem Cells"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e22331","DOI":"10.1096\/fj.202200010RR","article-title":"Hypoxia-induced blood-brain barrier dysfunction is prevented by pericyte-conditioned media via attenuated actomyosin contractility and claudin-5 stabilization","volume":"36","author":"Jamieson","year":"2022","journal-title":"FASEB J."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"F68","DOI":"10.1152\/ajprenal.00270.2021","article-title":"Effects of caloric restriction and aerobic exercise on circulating cell-free mitochondrial DNA in patients with moderate to severe chronic kidney disease","volume":"322","author":"Jaramillo-Morales","year":"2022","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"725","DOI":"10.22038\/ijbms.2023.69551.15145","article-title":"Chronic stress-induced apoptosis is mitigated by young mitochondria transplantation in the prefrontal cortex of aged rats","volume":"26","author":"Javani","year":"2023","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1080\/14737175.2023.2250917","article-title":"Acute and long-term cognitive impairment following sepsis: mechanism and prevention","volume":"23","author":"Ji","year":"2023","journal-title":"Expert. Rev. Neurother."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"124194","DOI":"10.1016\/j.ijpharm.2024.124194","article-title":"Mitochondrial transplantation: a promising therapy for mitochondrial disorders","volume":"658","author":"Jiao","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2174\/1574888X17666220511153133","article-title":"Mesenchymal stem cells: new alternatives for nervous system disorders","volume":"18","author":"Jim\u00e9nez-Acosta","year":"2023","journal-title":"CSCR"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e70003","DOI":"10.1111\/jnc.70003","article-title":"Transcript and lipid profile alterations in astrocyte-neuron mitochondrial transfer under lipopolysaccharide exposure: an in vitro study","volume":"169","author":"Kan","year":"2025","journal-title":"J. Neurochem."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.2174\/1570159X05666220908100545","article-title":"The therapeutic potential of mitochondria transplantation therapy in neurodegenerative and neurovascular disorders","volume":"21","author":"Khan","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.3233\/JAD-200026","article-title":"Feasibility and efficacy of intra-arterial Administration of Embryonic Stem Cell Derived-Mesenchymal Stem Cells in animal model of Alzheimer\u2019s disease","volume":"76","author":"Kim","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.ard.2024.11.005","article-title":"Mitochondrial transplantation as a novel therapeutic approach in idiopathic inflammatory myopathy","volume":"84","author":"Kim","year":"2025","journal-title":"Ann. Rheum. Dis."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"488","DOI":"10.5483\/BMBRep.2023-0098","article-title":"Mitochondrial transplantation: an overview of a promising therapeutic approach","volume":"56","author":"Kim","year":"2023","journal-title":"BMB Rep."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"301","DOI":"10.55730\/1300-0152.2665","article-title":"Mitochondrial transplantation and transfer: the promising method for diseases","volume":"47","author":"Kubat","year":"2023","journal-title":"Turk. J. Biol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1326-9-16","article-title":"Increased mtDNA mutations with aging promotes amyloid accumulation and brain atrophy in the APP\/Ld transgenic mouse model of Alzheimer\u2019s disease","volume":"9","author":"Kukreja","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s12904-020-00669-z","article-title":"Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial","volume":"19","author":"Lawlor","year":"2020","journal-title":"BMC Palliat. Care"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1144036","DOI":"10.3389\/fnagi.2023.1144036","article-title":"Imaging blood\u2013brain barrier disruption in neuroinflammation and Alzheimer\u2019s disease","volume":"15","author":"Lee","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e28974","DOI":"10.1016\/j.heliyon.2024.e28974","article-title":"Mitochondrial dysfunction precedes hippocampal IL-1\u03b2 transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice","volume":"10","author":"Lee","year":"2024","journal-title":"Heliyon"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.3346\/jkms.2020.35.e16","article-title":"Frailty and comprehensive geriatric assessment","volume":"35","author":"Lee","year":"2020","journal-title":"J. Korean Med. Sci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1451989","DOI":"10.3389\/fimmu.2024.1451989","article-title":"Advancements in mitochondrial-targeted nanotherapeutics: overcoming biological obstacles and optimizing drug delivery","volume":"15","author":"Li","year":"2024","journal-title":"Front. Immunol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1186\/s40001-025-02699-w","article-title":"The role of mitochondrial dysfunction in the pathogenesis of Alzheimer\u2019s disease and future strategies for targeted therapy","volume":"30","author":"Li","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3791\/63116","article-title":"Flow cytometric analysis of multiple mitochondrial parameters in human induced pluripotent stem cells and their neural and glial derivatives","volume":"117","author":"Liang","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"800883","DOI":"10.3389\/fnins.2022.800883","article-title":"Mitochondrial transplantation attenuates neural damage and improves locomotor function after traumatic spinal cord injury in rats","volume":"16","author":"Lin","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"680672","DOI":"10.3389\/fnagi.2021.680672","article-title":"Subjective cognitive decline may be associated with post-operative delirium in patients undergoing Total hip replacement: the PNDABLE study","volume":"13","author":"Lin","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"111212","DOI":"10.1016\/j.mad.2020.111212","article-title":"Mitochondrial fission and fusion: A dynamic role in aging and potential target for age-related disease","volume":"186","author":"Liu","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1097\/EJA.0000000000001620","article-title":"Mitochondrial DNA methylation drift and postoperative delirium in mice","volume":"39","author":"Liu","year":"2022","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"844","DOI":"10.18632\/aging.102659","article-title":"Surgery\/anesthesia disturbs mitochondrial fission\/fusion dynamics in the brain of aged mice with postoperative delirium","volume":"12","author":"Lu","year":"2020","journal-title":"Aging"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00415-025-13104-1","article-title":"The intersection of delirium and long-term cognition in older adults: the critical role of delirium prevention","volume":"272","author":"Lu","year":"2025","journal-title":"J. Neurol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1002\/cpz1.34","article-title":"Immunopurification of mitochondria from Arabidopsis","volume":"1","author":"Luo","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1542369","DOI":"10.3389\/fimmu.2025.1542369","article-title":"Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation","volume":"16","author":"Ma","year":"2025","journal-title":"Front. Immunol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3390\/neurosci6030086","article-title":"Accuracy of the Mini-mental state examination and Montreal cognitive assessment in detecting cognitive impairment in older adults: A comparative study adjusted for educational level","volume":"6","author":"Maduro","year":"2025","journal-title":"NeuroSci"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1080\/15548627.2022.2038898","article-title":"Mitochondrial respiration supports autophagy to provide stress resistance during quiescence","volume":"18","author":"Magalhaes-Novais","year":"2022","journal-title":"Autophagy"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s13063-026-09592-9","article-title":"Views on consent approaches used in emergency and critical care research: a rapid, systematic review","volume":"27","author":"Mahon","year":"2026","journal-title":"Trials"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"e70411","DOI":"10.1002\/alz.70411","article-title":"Multimorbidity patterns and blood biomarkers of Alzheimer\u2019s disease in community-dwelling cognitively unimpaired older adults","volume":"21","author":"Marengoni","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"ITC49","DOI":"10.7326\/AITC202010060","article-title":"Delirium","volume":"173","author":"Mattison","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1001\/jamaneurol.2019.0765","article-title":"Association between longitudinal plasma Neurofilament light and neurodegeneration in patients with Alzheimer disease","volume":"76","author":"Mattsson","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"e70253","DOI":"10.1002\/mco2.70253","article-title":"Mitochondrial transplantation: A novel therapeutic approach for treating diseases","volume":"6","author":"Miao","year":"2025","journal-title":"MedComm"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"148544","DOI":"10.1016\/j.brainres.2023.148544","article-title":"Mitochondria transfer as a potential therapeutic mechanism in Alzheimer\u2019s disease-like pathology","volume":"1819","author":"Mishra","year":"2023","journal-title":"Brain Res."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s41999-019-00261-6","article-title":"Delirium superimposed on dementia","volume":"11","author":"Morandi","year":"2020","journal-title":"Eur Geriatr Med"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jamda.2016.07.014","article-title":"The diagnosis of delirium superimposed on dementia: an emerging challenge","volume":"18","author":"Morandi","year":"2017","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"e70170","DOI":"10.1111\/jnc.70170","article-title":"Neural stem cell-derived extracellular vesicles for advanced neural repair","volume":"169","author":"Moretti","year":"2025","journal-title":"J. Neurochem."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"e038457","DOI":"10.1161\/JAHA.124.038457","article-title":"Pericytes and extracellular vesicle interactions in neurovascular adaptation to chronic arterial hypertension","volume":"14","author":"Morton","year":"2025","journal-title":"JAHA"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1001\/jamaneurol.2020.4986","article-title":"Longitudinal associations of blood phosphorylated Tau181 and Neurofilament light chain with neurodegeneration in Alzheimer disease","volume":"78","author":"Moscoso","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3390\/antiox14101259","article-title":"Stress pathways in chronic kidney disease: linking cortisol, oxidative stress, and inflammation","volume":"14","author":"Motrenikova","year":"2025","journal-title":"Antioxidants"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3233\/ADR-220103","article-title":"Barriers to using legally authorized representatives in clinical research with older adults","volume":"7","author":"Mozersky","year":"2023","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3233\/JAD-190853","article-title":"Mitochondrial transfer ameliorates cognitive deficits, neuronal loss, and gliosis in Alzheimer\u2019s disease mice","volume":"72","author":"Nitzan","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41536-020-00107-x","article-title":"Mitochondrial dysfunction in neurological disorders: exploring mitochondrial transplantation","volume":"5","author":"Norat","year":"2020","journal-title":"NPJ Regener. Med."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12929-018-0429-1","article-title":"Regenerative abilities of mesenchymal stem cells through mitochondrial transfer","volume":"25","author":"Paliwal","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12967-024-04908-2","article-title":"Intranasal delivery of mitochondria targeted neuroprotective compounds for traumatic brain injury: screening based on pharmacological and physiological properties","volume":"22","author":"Pandya","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"118833","DOI":"10.1016\/j.lfs.2020.118833","article-title":"Autophagy alleviates mitochondrial DAMP-induced acute lung injury by inhibiting NLRP3 inflammasome","volume":"265","author":"Peng","year":"2021","journal-title":"Life Sci."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.freeradbiomed.2025.06.040","article-title":"Therapeutic transplantation of mitochondria and extracellular vesicles: mechanistic insights into mitochondria bioenergetics, redox signaling, and organelle dynamics in preclinical models","volume":"238","author":"Perrier","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e3001166","DOI":"10.1371\/journal.pbio.3001166","article-title":"Neural stem cells traffic functional mitochondria via extracellular vesicles","volume":"19","author":"Peruzzotti-Jametti","year":"2021","journal-title":"PLoS Biol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.3390\/ijms23042245","article-title":"Promising treatment for multiple sclerosis: mitochondrial transplantation","volume":"23","author":"Picone","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.athoracsur.2025.10.028","article-title":"Clinical frailty scale assessment before cardiac surgery","volume":"121","author":"Pienta","year":"2026","journal-title":"Ann. Thorac. Surg."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1016\/j.neurobiolaging.2013.04.014","article-title":"Mitochondrial DNA damage in a mouse model of Alzheimer\u2019s disease decreases amyloid beta plaque formation","volume":"34","author":"Pinto","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3390\/bios16010066","article-title":"Smart biosensing nanomaterials for Alzheimer\u2019s disease: advances in design and drug delivery strategies to overcome the blood\u2013brain barrier","volume":"16","author":"Rajkumar","year":"2026","journal-title":"Biosensors"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/eahr.500091","article-title":"Advance research directives: dementia researchers\u2019 views on a prototype directive and implementation strategies","volume":"43","author":"Ries","year":"2021","journal-title":"Ethics Hum. Res."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"105971","DOI":"10.1016\/j.neubiorev.2024.105971","article-title":"Mitochondrial transplantation in brain disorders: achievements, methods, and challenges","volume":"169","author":"Riou","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"e616","DOI":"10.1097\/TXD.0000000000001065","article-title":"Rejection-associated mitochondrial impairment after heart transplantation","volume":"6","author":"Romero","year":"2020","journal-title":"Transplant. Direct"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s10616-025-00805-8","article-title":"Unlocking the potential of mitochondrial transplantation: overcoming challenges and paving the way for routine therapeutic application","volume":"77","author":"Roushandeh","year":"2025","journal-title":"Cytotechnology"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/0115672050395356251106100427","article-title":"Advances in nose-to-brain delivery systems for effective Alzheimer\u2019s disease management","volume":"23","author":"Sahu","year":"2026","journal-title":"Curr. Alzheimer Res."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3390\/cells9061443","article-title":"MiRNA profiling in plasma neural-derived small extracellular vesicles from patients with Alzheimer\u2019s disease","volume":"9","author":"Serpente","year":"2020","journal-title":"Cells"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/j.cell.2025.01.017","article-title":"Engineered commensals for targeted nose-to-brain drug delivery","volume":"188","author":"Shen","year":"2025","journal-title":"Cell"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1186\/s13287-025-04792-7","article-title":"Therapeutic potential and mechanistic insights into adipose-derived stem cells and mesenchymal stem cell-derived exosomes in patients with Crohn\u2019s disease-associated fistulas: challenges and future perspectives","volume":"16","author":"Sheykhhasan","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"112042","DOI":"10.1016\/j.biopha.2021.112042","article-title":"Immunomodulation effect of mesenchymal stem cells in islet transplantation","volume":"142","author":"Shrestha","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3390\/cells14030229","article-title":"Mitochondrial alterations, oxidative stress, and therapeutic implications in Alzheimer\u2019s disease: A narrative review","volume":"14","author":"Spina","year":"2025","journal-title":"Cells"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.hrtlng.2023.02.010","article-title":"Plasma biomarkers and delirium in critically ill patients after cardiac surgery: A prospective observational cohort study","volume":"59","author":"Su","year":"2023","journal-title":"Heart Lung"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/cells12071006","article-title":"The beneficial effect of mitochondrial transfer therapy in 5XFAD mice via liver\u2013serum\u2013brain response","volume":"12","author":"Sweetat","year":"2023","journal-title":"Cells"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"3350","DOI":"10.1038\/s41598-025-86760-y","article-title":"The role of homogenization cycles and Poloxamer 188 on the quality of mitochondria isolated for use in mitochondrial transplantation therapy","volume":"15","author":"Takegawa","year":"2025","journal-title":"Sci. Rep."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.3390\/genes12101604","article-title":"Interrogating mitochondrial biology and disease using CRISPR\/Cas9 gene editing","volume":"12","author":"Tang","year":"2021","journal-title":"Genes"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3390\/cells14030151","article-title":"In vivo and in vitro evaluation of the feasibility and safety profiles of intraarticular transplantation of mitochondria for future use as a therapy for osteoarthritis","volume":"14","author":"Vaamonde-Garcia","year":"2025","journal-title":"Cells"},{"key":"ref110","doi-asserted-by":"publisher","DOI":"10.3791\/67093","article-title":"Robust mitochondrial isolation from rodent cardiac tissue","author":"Vadovsky","year":"2024","journal-title":"J. Visual. Exp."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"14683","DOI":"10.1007\/s12035-025-05026-w","article-title":"Exploring exosome-based approaches for early diagnosis and treatment of neurodegenerative diseases","volume":"62","author":"Varshney","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"103377","DOI":"10.1016\/j.gerinurse.2025.05.016","article-title":"Geriatric syndromes associated with long-term mortality in adults aged 90 years and older","volume":"64","author":"Veizi","year":"2025","journal-title":"Geriatr. Nurs."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1089\/nat.2024.0067","article-title":"Exosome-mediated mitochondrial delivery of antisense oligonucleotides","volume":"35","author":"Von Trentini","year":"2025","journal-title":"Nucleic Acid Ther."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"147","DOI":"10.34172\/apb.2024.019","article-title":"Potential applications of mitochondrial therapy with a focus on Parkinson\u2019s disease and mitochondrial transplantation","volume":"14","author":"Wal","year":"2023","journal-title":"Adv Pharm Bull"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1177\/0271678X241305230","article-title":"Autologous mitochondrial transplant for acute cerebral ischemia: phase 1 trial results and review","volume":"46","author":"Walker","year":"2026","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"1801896","DOI":"10.3389\/fimmu.2026.1801896","article-title":"Gasdermin D-driven pyroptosis in sepsis: mechanisms, therapeutic strategies, and clinical translation","volume":"17","author":"Wang","year":"2026","journal-title":"Front. Immunol."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1002\/alz.12064","article-title":"Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia","volume":"16","author":"Wang","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"012005","DOI":"10.1088\/1758-5090\/ae3526","article-title":"Biofabrication of 3D bioprinted and organ-on-chip blood\u2013brain barrier models using hCMEC\/D3 for intranasal delivery of central nervous system therapeutics","volume":"18","author":"Wong","year":"2026","journal-title":"Biofabrication"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.3233\/JAD-230293","article-title":"Ameliorative role of mitochondrial therapy in cognitive function of vascular dementia mice","volume":"97","author":"Wu","year":"2024","journal-title":"JAD"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"101924","DOI":"10.1016\/j.mito.2024.101924","article-title":"Neuroprotective effect of autologous mitochondrial transplantation against global ischemia\/reperfusion injury in a rat model of cardiac arrest","volume":"78","author":"Xu","year":"2024","journal-title":"Mitochondrion"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"6703","DOI":"10.1007\/s12035-024-04368-1","article-title":"Mitochondrial treatment improves cognitive impairment induced by lipopolysaccharide in mice","volume":"62","author":"Yan","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"3875","DOI":"10.1007\/s12035-020-01994-3","article-title":"Mitochondrial transplantation attenuates brain dysfunction in sepsis by driving microglial M2 polarization","volume":"57","author":"Yan","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"225","DOI":"10.5599\/admet.2160","article-title":"Frontiers of stem cell engineering for nanotechnology-mediated drug delivery systems","volume":"12","author":"Ye\u015filk\u0131r Baydar","year":"2024","journal-title":"ADMET DMPK"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/s41467-025-68024-5","article-title":"Intranasal blood-brain barrier bypass enables sequential mitochondria-targeted bioengineered nanolamellar system for ischemic stroke therapy","volume":"17","author":"Yin","year":"2026","journal-title":"Nat. Commun."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"1114595","DOI":"10.3389\/fphys.2023.1114595","article-title":"Rapid isolation of respiring skeletal muscle mitochondria using nitrogen cavitation","volume":"14","author":"Younis","year":"2023","journal-title":"Front. Physiol."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.neurobiolaging.2014.10.040","article-title":"Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer\u2019s disease\u2013like pathology","volume":"36","author":"Zhang","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/s12967-023-04134-2","article-title":"Preventative effect of TSPO ligands on mixed antibody-mediated rejection through a mitochondria-mediated metabolic disorder","volume":"21","author":"Zhang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.apsb.2022.10.008","article-title":"Mitochondrial transplantation as a promising therapy for mitochondrial diseases","volume":"13","author":"Zhang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.3233\/JAD-200686","article-title":"Mesenchymal stem cell-conditioned medium improves mitochondrial dysfunction and suppresses apoptosis in Okadaic acid-treated SH-SY5Y cells by extracellular vesicle mitochondrial transfer","volume":"78","author":"Zhang","year":"2020","journal-title":"JAD"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"849","DOI":"10.7150\/ijbs.40886","article-title":"Improvement of cognitive and motor performance with mitotherapy in aged mice","volume":"16","author":"Zhao","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1186\/s40001-023-01245-w","article-title":"Causal relationships between delirium and Alzheimer\u2019s disease: a bidirectional two-sample Mendelian randomization study","volume":"28","author":"Zheng","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"e134","DOI":"10.1002\/smmd.134","article-title":"Biomineralize mitochondria in metal-organic frameworks to promote mitochondria transplantation from non-tumorigenic cells into cancer cells","volume":"4","author":"Zhou","year":"2025","journal-title":"Smart Med."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"e10473","DOI":"10.1002\/btm2.10473","article-title":"Photobiomodulation augments the effects of mitochondrial transplantation in the treatment of spinal cord injury in rats by facilitating mitochondrial transfer to neurons via Connexin 36","volume":"8","author":"Zhu","year":"2023","journal-title":"Bioeng. Transla Med"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1885815\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:27:44Z","timestamp":1786080464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1885815\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":133,"alternative-id":["10.3389\/fnagi.2026.1885815"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1885815","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1885815"}}