{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:00:40Z","timestamp":1790614840807,"version":"4.1.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372557"],"award-info":[{"award-number":["82372557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Capital Funds for Health Improvement and Research","award":["2022-1-2251"],"award-info":[{"award-number":["2022-1-2251"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-026-06228-6","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:16:12Z","timestamp":1790565372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cognitive-Motor Dual Task Training Synergistically Improves Aging-related Cognitive Dysfunction By Reducing TMAO and Suppressing TXNIP\/NLRP3 Pathway"],"prefix":"10.1007","volume":"63","author":[{"given":"Rong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengteng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziman","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"12","key":"6228_CR1","doi-asserted-by":"publisher","first-page":"e661","DOI":"10.1016\/S2468-2667(20)30185-7","volume":"5","author":"L Jia","year":"2020","unstructured":"Jia L, Du Y, Chu L et al (2020) Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Lancet Public Health 5(12):e661\u2013e671. https:\/\/doi.org\/10.1016\/S2468-2667(20)30185-7","journal-title":"Lancet Public Health"},{"key":"6228_CR2","doi-asserted-by":"publisher","unstructured":"2024 Alzheimer's disease facts and figures. (2024).\u00a0Alzheimer's & dementia : the journal of the Alzheimer's Association 20(5) 3708\u20133821. https:\/\/doi.org\/10.1002\/alz.13809","DOI":"10.1002\/alz.13809"},{"issue":"2","key":"6228_CR3","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L et al (2023) Hallmarks of aging: an expanding universe. Cell 186(2):243\u2013278. https:\/\/doi.org\/10.1016\/j.cell.2022.11.001","journal-title":"Cell"},{"key":"6228_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100912","volume":"53","author":"L Nguyen","year":"2019","unstructured":"Nguyen L, Murphy K, Andrews G (2019) Cognitive and neural plasticity in old age: a systematic review of evidence from executive functions cognitive training. Ageing Res Rev 53:100912. https:\/\/doi.org\/10.1016\/j.arr.2019.100912","journal-title":"Ageing Res Rev"},{"key":"6228_CR5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/978-3-031-75980-2_2","volume":"108","author":"B van Zundert","year":"2025","unstructured":"van Zundert B, Montecino M (2025) Epigenetics in Learning and Memory. Subcell Biochem 108:51\u201371. https:\/\/doi.org\/10.1007\/978-3-031-75980-2_2","journal-title":"Subcell Biochem"},{"issue":"2","key":"6228_CR6","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1007\/s13311-018-00698-","volume":"16","author":"QG Ren","year":"2019","unstructured":"Ren QG, Gong WG, Zhou H, Shu H, Wang YJ, Zhang ZJ (2019) Spatial training ameliorates long-term alzheimer\u2019s disease-like pathological deficits by reducing NLRP3 inflammasomes in PR5 Mice. Neurotherapeutics\u202f:J American Soc Experimental Neurotherapeutics 16(2):450\u2013464. https:\/\/doi.org\/10.1007\/s13311-018-00698-","journal-title":"Neurotherapeutics :J American Soc Experimental Neurotherapeutics"},{"key":"6228_CR7","doi-asserted-by":"publisher","unstructured":"Jiang HY, Zhang X, Yu et al (2018) Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatric Res 104 130\u2013136. https:\/\/doi.org\/10.1016\/j.jpsychires.2018.07.007","DOI":"10.1016\/j.jpsychires.2018.07.007"},{"issue":"7889","key":"6228_CR8","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-021-04183-x","volume":"600","author":"Z De Miguel","year":"2021","unstructured":"De Miguel Z, Khoury N, Betley MJ et al (2021) Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature 600(7889):494\u2013499. https:\/\/doi.org\/10.1038\/s41586-021-04183-x","journal-title":"Nature"},{"issue":"21","key":"6228_CR9","doi-asserted-by":"publisher","first-page":"e2245","DOI":"10.1212\/WNL.0000000000009478","volume":"94","author":"V Guadagni","year":"2020","unstructured":"Guadagni V, Drogos LL, Tyndall AV et al (2020) Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology 94(21):e2245\u2013e2257. https:\/\/doi.org\/10.1212\/WNL.0000000000009478","journal-title":"Neurology"},{"issue":"9","key":"6228_CR10","doi-asserted-by":"publisher","first-page":"3316","DOI":"10.1073\/pnas.0400266101","volume":"101","author":"SJ Colcombe","year":"2004","unstructured":"Colcombe SJ, Kramer AF, Erickson KI et al (2004) Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci U S A 101(9):3316\u20133321. https:\/\/doi.org\/10.1073\/pnas.0400266101","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6228_CR11","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.neuroimage.2017.11.007","volume":"166","author":"J Firth","year":"2018","unstructured":"Firth J, Stubbs B, Vancampfort D et al (2018) Effect of aerobic exercise on hippocampal volume in humans: a systematic review and meta-analysis. Neuroimage 166:230\u2013238. https:\/\/doi.org\/10.1016\/j.neuroimage.2017.11.007","journal-title":"Neuroimage"},{"key":"6228_CR12","doi-asserted-by":"publisher","unstructured":"TTao X, Zhang R, Wang L et al (2023) Luteolin and exercise combination therapy ameliorates amyloid-\u03b21\u201342 oligomers-induced cognitive impairment in AD mice by mediating neuroinflammation and autophagy. J Alzheimers Dis 92 (1) 195\u2013208. https:\/\/doi.org\/10.3233\/JAD-220904","DOI":"10.3233\/JAD-220904"},{"key":"6228_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2022.105459","volume":"162","author":"Y Zhang","year":"2023","unstructured":"Zhang Y, Wang G, Li R et al (2023) Trimethylamine N-oxide aggravated cognitive impairment from APP\/PS1 mice and protective roles of voluntary exercise. Neurochem Int 162:105459. https:\/\/doi.org\/10.1016\/j.neuint.2022.105459","journal-title":"Neurochem Int"},{"key":"6228_CR14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.neurobiolaging.2017.10.003","volume":"62","author":"MA Motes","year":"2018","unstructured":"Motes MA, Yezhuvath US, Aslan S et al (2018) Higher-order cognitive training effects on processing speed-related neural activity: a randomized trial. Neurobiol Aging 62:72\u201381. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2017.10.003","journal-title":"Neurobiol Aging"},{"key":"6228_CR15","doi-asserted-by":"publisher","unstructured":"Zhang R, Li L, Xi X et al (2026) Exercise training mitigates age-related cognitive decline by attenuating TMAO-induced inflammation. Sci Rep 20. https:\/\/doi.org\/10.1038\/s41598-026-36354-z","DOI":"10.1038\/s41598-026-36354-z"},{"key":"6228_CR16","doi-asserted-by":"publisher","first-page":"1051056","DOI":"10.3389\/fnagi.2022.1051056","volume":"14","author":"X Tao","year":"2022","unstructured":"Tao X, Sun R, Han C et al (2022) Cognitive-motor dual task: an effective rehabilitation method in aging-related cognitive impairment. Front Aging Neurosci 14:1051056. https:\/\/doi.org\/10.3389\/fnagi.2022.1051056","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"6228_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-026-00860-9","volume":"31","author":"ZM Zhu","year":"2026","unstructured":"Zhu ZM, Dai TT, Zhang R et al (2026) Cognitive-exercise dual-task training delays natural aging\/D-galactose-induced cognitive decline in mice. Cell Mol Biol Lett 31(1):32. https:\/\/doi.org\/10.1186\/s11658-026-00860-9","journal-title":"Cell Mol Biol Lett"},{"key":"6228_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110761","volume":"202","author":"T Li","year":"2023","unstructured":"Li T, Tao X, Sun R et al (2023) Cognitive-exercise dual-task intervention ameliorates cognitive decline in natural aging rats via inhibiting the promotion of LncRNA NEAT1\/miR-124-3p on caveolin-1-PI3K\/Akt\/GSK3\u03b2 pathway. Brain Res Bull 202:110761. https:\/\/doi.org\/10.1016\/j.brainresbull.2023.110761","journal-title":"Brain Res Bull"},{"key":"6228_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111981","volume":"169","author":"XL Li","year":"2022","unstructured":"Li XL, Tao X, Li TC et al (2022) Cognitive-exercise dual-task intervention ameliorates cognitive decline in natural aging rats through reducing oxidative stress and enhancing synaptic plasticity. Exp Gerontol 169:111981. https:\/\/doi.org\/10.1016\/j.exger.2022.111981","journal-title":"Exp Gerontol"},{"issue":"9","key":"6228_CR20","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/j.jagp.2022.01.011","volume":"30","author":"X Zhu","year":"2022","unstructured":"Zhu X, Yin S, Huo L et al (2022) A multimodal intervention to improve cognition in community-dwelling older adults. Am J Geriatr Psychiatry 30(9):1003\u20131014. https:\/\/doi.org\/10.1016\/j.jagp.2022.01.011","journal-title":"Am J Geriatr Psychiatry"},{"key":"6228_CR21","doi-asserted-by":"publisher","first-page":"105946","DOI":"10.1016\/j.archger.2025.105946","volume":"137","author":"Y Guan","year":"2025","unstructured":"Guan Y, Hu Z, Wang Q et al (2025) Effectiveness of interventions to improve frailty among community-dwelled older adults: a systematic review. Arch Gerontol Geriatr 137:105946. https:\/\/doi.org\/10.1016\/j.archger.2025.105946","journal-title":"Arch Gerontol Geriatr"},{"issue":"3","key":"6228_CR22","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s40572-016-0100-5","volume":"3","author":"CA Lowry","year":"2016","unstructured":"Lowry CA, Smith DG, Siebler PH et al (2016) The microbiota, immunoregulation, and mental health: implications for public health. Curr Environ Health Rep 3(3):270\u2013286. https:\/\/doi.org\/10.1007\/s40572-016-0100-5","journal-title":"Curr Environ Health Rep"},{"key":"6228_CR23","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.mad.2013.12.004","volume":"136-137","author":"M Candela","year":"2014","unstructured":"Candela M, Biagi E, Brigidi P et al (2014) Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach. Mech Ageing Dev 136\u2013137:70\u201375. https:\/\/doi.org\/10.1016\/j.mad.2013.12.004","journal-title":"Mech Ageing Dev"},{"key":"6228_CR24","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3389\/fmicb.2014.00764","volume":"5","author":"S Saraswati","year":"2015","unstructured":"Saraswati S, Sitaraman R (2015) Aging and the human gut microbiota-from correlation to causality. Front Microbiol 5:764. https:\/\/doi.org\/10.3389\/fmicb.2014.00764","journal-title":"Front Microbiol"},{"issue":"6","key":"6228_CR25","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002816","volume":"5","author":"V Senthong","year":"2016","unstructured":"Senthong V, Wang Z, Li XS et al (2016) Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc 5(6):e002816. https:\/\/doi.org\/10.1161\/JAHA.115.002816","journal-title":"J Am Heart Assoc"},{"issue":"11","key":"6228_CR26","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1161\/CIRCRESAHA.125.325516","volume":"136","author":"M Snelson","year":"2025","unstructured":"Snelson M, R Muralitharan R, Liu CF et al (2025) Gut-heart axis: the role of gut microbiota and metabolites in heart failure. Circ Res 136(11):1382\u20131406. https:\/\/doi.org\/10.1161\/CIRCRESAHA.125.325516","journal-title":"Circ Res"},{"issue":"3","key":"6228_CR27","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","volume":"116","author":"WH Tang","year":"2015","unstructured":"Tang WH, Wang Z, Kennedy DJ et al (2015) Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res 116(3):448\u2013455. https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.305360","journal-title":"Circ Res"},{"issue":"Suppl 3","key":"6228_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12918-016-0307-y","volume":"10","author":"R Xu","year":"2016","unstructured":"Xu R, Wang Q (2016) Towards understanding brain-gut-microbiome connections in Alzheimer\u2019s disease. BMC Syst Biol 10(Suppl 3):63. https:\/\/doi.org\/10.1186\/s12918-016-0307-y","journal-title":"BMC Syst Biol"},{"issue":"10","key":"6228_CR29","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.3390\/nu9101053","volume":"9","author":"D el Rio","year":"2017","unstructured":"el Rio D, Zimetti F, Caffarra P et al (2017) The gut microbial metabolite trimethylamine-N-oxide is present in human cerebrospinal fluid. Nutrients 9(10):1053. https:\/\/doi.org\/10.3390\/nu9101053","journal-title":"Nutrients"},{"key":"6228_CR30","doi-asserted-by":"publisher","unstructured":"VVernetti L, Gough A, Baetz N et al (2017) Corrigendum: functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci Rep 7 44517. https:\/\/doi.org\/10.1038\/srep44517","DOI":"10.1038\/srep44517"},{"issue":"1","key":"6228_CR31","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13195-018-0451-2","volume":"10","author":"NM Vogt","year":"2018","unstructured":"Vogt NM, Romano KA, Darst BF et al (2018) The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer\u2019s disease. Alzheimers Res Ther 10(1):124. https:\/\/doi.org\/10.1186\/s13195-018-0451-2","journal-title":"Alzheimers Res Ther"},{"issue":"4","key":"6228_CR32","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12768","volume":"17","author":"D Li","year":"2018","unstructured":"Li D, Ke Y, Zhan R et al (2018) Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell 17(4):e12768. https:\/\/doi.org\/10.1111\/acel.12768","journal-title":"Aging Cell"},{"key":"6228_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105277","volume":"164","author":"M Koszewicz","year":"2021","unstructured":"Koszewicz M, Jaroch J, Brzecka A et al (2021) Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment. Pharmacol Res 164:105277. https:\/\/doi.org\/10.1016\/j.phrs.2020.105277","journal-title":"Pharmacol Res"},{"issue":"1","key":"6228_CR34","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/imr.12295","volume":"265","author":"EL Goldberg","year":"2015","unstructured":"Goldberg EL, Dixit VD (2015) Drivers of age-related inflammation and strategies for healthspan extension. Immunol Rev 265(1):63\u201374. https:\/\/doi.org\/10.1111\/imr.12295","journal-title":"Immunol Rev"},{"issue":"7575","key":"6228_CR35","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nature15514","volume":"526","author":"J Shi","year":"2015","unstructured":"Shi J, Zhao Y, Wang K et al (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660\u2013665. https:\/\/doi.org\/10.1038\/nature15514","journal-title":"Nature"},{"key":"6228_CR36","doi-asserted-by":"publisher","first-page":"115025","DOI":"10.1016\/j.intimp.2025.115025","volume":"161","author":"D Huang","year":"2025","unstructured":"Huang D, Xu D, You C et al (2025) Caspase-8-driven NLRP3 inflammasome activation exacerbates bronchopulmonary dysplasia by increasing the apoptosis and pyroptosis crosstalk of alveolar epithelial cells. Int Immunopharmacol 161:115025. https:\/\/doi.org\/10.1016\/j.intimp.2025.115025","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"6228_CR37","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1186\/s12951-022-01524-4","volume":"20","author":"Y Ruan","year":"2022","unstructured":"Ruan Y, Xiong Y, Fang W et al (2022) Highly sensitive curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer\u2019s disease via NLRP3-inhibition. J Nanobiotechnol 20(1):322. https:\/\/doi.org\/10.1186\/s12951-022-01524-4","journal-title":"J Nanobiotechnol"},{"key":"6228_CR38","doi-asserted-by":"publisher","first-page":"794770","DOI":"10.3389\/fimmu.2021.794770","volume":"12","author":"R Que","year":"2021","unstructured":"Que R, Zheng J, Chang Z et al (2021) Dl-3-n-Butylphthalide rescues dopaminergic neurons in Parkinson\u2019s disease models by inhibiting the NLRP3 inflammasome and ameliorating mitochondrial impairment. Front Immunol 12:794770. https:\/\/doi.org\/10.3389\/fimmu.2021.794770","journal-title":"Front Immunol"},{"issue":"1","key":"6228_CR39","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1159\/000484623","volume":"44","author":"KM Boini","year":"2017","unstructured":"Boini KM, Hussain T, Li PL et al (2017) Trimethylamine-N-oxide instigates NLRP3 inflammasome activation and endothelial dysfunction. Cell Physiol Biochem 44(1):152\u2013162. https:\/\/doi.org\/10.1159\/000484623","journal-title":"Cell Physiol Biochem"},{"issue":"4","key":"6228_CR40","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1182\/blood.201900399010.1182\/blood.2019003990","volume":"136","author":"K Wu","year":"2020","unstructured":"Wu K, Yuan Y, Yu H et al (2020) The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood 136(4):501\u2013515. https:\/\/doi.org\/10.1182\/blood.201900399010.1182\/blood.2019003990","journal-title":"Blood"},{"issue":"12","key":"6228_CR41","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1007\/s10495-017-1414-y","volume":"22","author":"X Yuan","year":"2017","unstructured":"Yuan X, Zheng Y, Chen C et al (2017) Anisodamine inhibits endoplasmic reticulum stress-associated TXNIP\/NLRP3 inflammasome activation in rhabdomyolysis-induced acute kidney injury. Apoptosis 22(12):1524\u20131531. https:\/\/doi.org\/10.1007\/s10495-017-1414-y","journal-title":"Apoptosis"},{"issue":"11","key":"6228_CR42","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1007\/s00011-016-0973-7","volume":"65","author":"L Jiang","year":"2016","unstructured":"Jiang L, Fei D, Gong R et al (2016) CORM-2 inhibits TXNIP\/NLRP3 inflammasome pathway in LPS-induced acute lung injury. Inflamm Res 65(11):905\u2013915. https:\/\/doi.org\/10.1007\/s00011-016-0973-7","journal-title":"Inflamm Res"},{"issue":"2","key":"6228_CR43","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ni.1831","volume":"11","author":"R Zhou","year":"2010","unstructured":"Zhou R, Tardivel A, Thorens B et al (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 11(2):136\u2013140. https:\/\/doi.org\/10.1038\/ni.1831","journal-title":"Nat Immunol"},{"key":"6228_CR44","doi-asserted-by":"publisher","unstructured":"Cao Z, Fang Y, Lu Y et al (2017) Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome. J Pineal Res 62 (3). https:\/\/doi.org\/10.1111\/jpi.12389","DOI":"10.1111\/jpi.12389"},{"key":"6228_CR45","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6521146","author":"B Zhang","year":"2021","unstructured":"Zhang B, Lian W, Zhao J et al (2021) DL0410 alleviates memory impairment in D-Galactose-induced aging rats by suppressing neuroinflammation via the TLR4\/MyD88\/NF-\u03baB pathway. Oxid Med Cell Longev. https:\/\/doi.org\/10.1155\/2021\/6521146","journal-title":"Oxid Med Cell Longev"},{"key":"6228_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151814","volume":"764","author":"J Li","year":"2025","unstructured":"Li J, Yuan R, Zheng S et al (2025) Exploring the impact of Gastrodin on brain aging in mice: unraveling mechanisms through network pharmacology. Biochem Biophys Res Commun 764:151814. https:\/\/doi.org\/10.1016\/j.bbrc.2025.151814","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"6228_CR47","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1007\/s13668-024-00539-7","volume":"13","author":"\u015e Ayten","year":"2024","unstructured":"Ayten \u015e, Bilici S (2024) Modulation of gut microbiota through dietary intervention in neuroinflammation and Alzheimer\u2019s and Parkinson\u2019s diseases. Curr Nutr Rep 13(2):82\u201396. https:\/\/doi.org\/10.1007\/s13668-024-00539-7","journal-title":"Curr Nutr Rep"},{"issue":"1","key":"6228_CR48","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2302310","volume":"16","author":"Y Chen","year":"2024","unstructured":"Chen Y, Li Y, Fan Y et al (2024) Gut microbiota-driven metabolic alterations reveal gut-brain communication in Alzheimer\u2019s disease model mice. Gut Microbes 16(1):2302310. https:\/\/doi.org\/10.1080\/19490976.2024.2302310","journal-title":"Gut Microbes"},{"issue":"9","key":"6228_CR49","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.3390\/brainsci12091203","volume":"12","author":"X Chen","year":"2022","unstructured":"Chen X, Gu M, Hong Y et al (2022) Association of Trimethylamine N-Oxide with normal aging and neurocognitive disorders: a narrative review. Brain Sci 12(9):1203. https:\/\/doi.org\/10.3390\/brainsci12091203","journal-title":"Brain Sci"},{"issue":"3","key":"6228_CR50","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1161\/ATVBAHA.119.313414","volume":"40","author":"X Zhang","year":"2020","unstructured":"Zhang X, Li Y, Yang P et al (2020) Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-\u03baB Signals. Arterioscler Thromb Vasc Biol 40(3):751\u2013765. https:\/\/doi.org\/10.1161\/ATVBAHA.119.313414","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"21","key":"6228_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111864","volume":"22","author":"S Kapetanaki","year":"2021","unstructured":"Kapetanaki S, Kumawat AK, Persson K et al (2021) The fibrotic effects of TMAO on human renal fibroblasts is mediated by NLRP3, Caspase-1 and the PERK\/Akt\/mTOR pathway. Int J Mol Sci 22(21):11864. https:\/\/doi.org\/10.3390\/ijms222111864","journal-title":"Int J Mol Sci"},{"key":"6228_CR52","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.freeradbiomed.2018.01.007","volume":"116","author":"Y Ke","year":"2018","unstructured":"Ke Y, Li D, Zhao M et al (2018) Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radic Biol Med 116:88\u2013100. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2018.01.007","journal-title":"Free Radic Biol Med"},{"key":"6228_CR53","doi-asserted-by":"publisher","first-page":"3699","DOI":"10.2147\/JIR.S399480","volume":"16","author":"P Ge","year":"2023","unstructured":"Ge P, Duan H, Tao C et al (2023) TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO\/IGF2BP2. J Inflamm Res 16:3699\u20133714. https:\/\/doi.org\/10.2147\/JIR.S399480","journal-title":"J Inflamm Res"},{"issue":"9","key":"6228_CR54","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006347","volume":"6","author":"ML Chen","year":"2017","unstructured":"Chen ML, Zhu XH, Ran L et al (2017) Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc 6(9):e006347. https:\/\/doi.org\/10.1161\/JAHA.117.006347","journal-title":"J Am Heart Assoc"},{"key":"6228_CR55","doi-asserted-by":"publisher","first-page":"944","DOI":"10.3389\/fphys.2017.00944","volume":"8","author":"H Zhang","year":"2017","unstructured":"Zhang H, Meng J, Yu H (2017) Trimethylamine N-oxide supplementation abolishes the cardioprotective effects of voluntary exercise in mice fed a Western diet. Front Physiol 8:944. https:\/\/doi.org\/10.3389\/fphys.2017.00944","journal-title":"Front Physiol"},{"key":"6228_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jnutbio.2017.12.010","volume":"56","author":"ML Battson","year":"2018","unstructured":"Battson ML, Lee DM, Weir TL et al (2018) The gut microbiota as a novel regulator of cardiovascular function and disease. J Nutr Biochem 56:1\u201315. https:\/\/doi.org\/10.1016\/j.jnutbio.2017.12.010","journal-title":"J Nutr Biochem"},{"issue":"2","key":"6228_CR57","doi-asserted-by":"publisher","first-page":"e001359","DOI":"10.1136\/bmjdrc-2020-001359","volume":"8","author":"S Argyridou","year":"2020","unstructured":"Argyridou S, Bernieh D, Henson J et al (2020) Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes. BMJ Open Diabetes Res Care 8(2):e001359. https:\/\/doi.org\/10.1136\/bmjdrc-2020-001359","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"1","key":"6228_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-024-04942-1","volume":"24","author":"JE Baek","year":"2024","unstructured":"Baek JE, Hyeon SJ, Kim M et al (2024) Effects of dual-task resistance exercise on cognition, mood, depression, functional fitness, and activities of daily living in older adults with cognitive impairment: a single-blinded, randomized controlled trial. BMC Geriatr 24(1):369. https:\/\/doi.org\/10.1186\/s12877-024-04942-1","journal-title":"BMC Geriatr"},{"issue":"2","key":"6228_CR59","doi-asserted-by":"publisher","first-page":"841","DOI":"10.3233\/JAD-201456","volume":"80","author":"T Tomoto","year":"2021","unstructured":"Tomoto T, Liu J, Tseng BY et al (2021) One-year aerobic exercise reduced carotid arterial stiffness and increased cerebral blood flow in amnestic mild cognitive impairment. J Alzheimers Dis 80(2):841\u2013853. https:\/\/doi.org\/10.3233\/JAD-201456","journal-title":"J Alzheimers Dis"},{"key":"6228_CR60","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.arr.2016.07.003","volume":"31","author":"X Zhu","year":"2016","unstructured":"Zhu X, Yin S, Lang M et al (2016) The more the better? A meta-analysis on effects of combined cognitive and physical intervention on cognition in healthy older adults. Ageing Res Rev 31:67\u201379. https:\/\/doi.org\/10.1016\/j.arr.2016.07.003","journal-title":"Ageing Res Rev"},{"issue":"1","key":"6228_CR61","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12966-018-0697-x","volume":"15","author":"F Gheysen","year":"2018","unstructured":"Gheysen F, Poppe L, DeSmet A et al (2018) Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis. Int J Behav Nutr Phys Act 15(1):63. https:\/\/doi.org\/10.1186\/s12966-018-0697-x","journal-title":"Int J Behav Nutr Phys Act"},{"key":"6228_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-14-103","volume":"14","author":"N Theill","year":"2013","unstructured":"Theill N, Schumacher V, Adelsberger R et al (2013) Effects of simultaneously performed cognitive and physical training in older adults. BMC Neurosci 14:103. https:\/\/doi.org\/10.1186\/1471-2202-14-103","journal-title":"BMC Neurosci"},{"key":"6228_CR63","doi-asserted-by":"publisher","first-page":"112662","DOI":"10.1016\/j.exger.2024.112662","volume":"200","author":"EM Ara\u00fajo","year":"2025","unstructured":"Ara\u00fajo EM, Coelho-J\u00fanior HJ, Sousa CV et al (2025) Improving serum redox balance, inflammatory status, physical function, and cognitive ability through dual-task resistance training and detraining in nursing home residents. Exp Gerontol 200:112662. https:\/\/doi.org\/10.1016\/j.exger.2024.112662","journal-title":"Exp Gerontol"},{"key":"6228_CR64","doi-asserted-by":"publisher","unstructured":"Wertman RS, Go CK, Saller BS et al (2024) Distinct sequential death complexes regulate pyroptosis and IL-1\u03b2 release in response to Yersinia blockade of immune signaling. Sci Adv 10 (30) eadl3629. https:\/\/doi.org\/10.1101\/2023.09.14.557714","DOI":"10.1101\/2023.09.14.557714"},{"key":"6228_CR65","doi-asserted-by":"publisher","first-page":"1412991","DOI":"10.3389\/fmicb.2024.1412991","volume":"15","author":"J Wu","year":"2024","unstructured":"Wu J, Shen H, Lv Y et al (2024) Age over sex: evaluating gut microbiota differences in healthy Chinese populations. Front Microbiol 15:1412991. https:\/\/doi.org\/10.3389\/fmicb.2024.1412991","journal-title":"Front Microbiol"},{"issue":"1","key":"6228_CR66","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s11357-020-00257-2","volume":"43","author":"VE Brunt","year":"2021","unstructured":"Brunt VE, LaRocca TJ, Bazzoni AE et al (2021) The gut microbiome-derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. GeroScience 43(1):377\u2013394. https:\/\/doi.org\/10.1007\/s11357-020-00257-2","journal-title":"GeroScience"},{"issue":"1","key":"6228_CR67","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13195-025-01846-z","volume":"17","author":"Y Shi","year":"2025","unstructured":"Shi Y, Wang P, Deng J et al (2025) Gut microbial metabolite TMAO impairs cognitive function and induces hippocampal synaptic plasticity decline through modulation of GSK-3\u03b2 activity. Alzheimers Res Ther 17(1):196. https:\/\/doi.org\/10.1186\/s13195-025-01846-z","journal-title":"Alzheimers Res Ther"},{"issue":"3","key":"6228_CR68","doi-asserted-by":"publisher","first-page":"G280","DOI":"10.1152\/ajpgi.00354.2025","volume":"330","author":"JM Cho","year":"2026","unstructured":"Cho JM, Park SK, Satheesh Babu AK et al (2026) Late-in-life treadmill training mitigates gut microbiome imbalances and cardiovascular disease risk in mice. Am J Physiol Gastrointest Liver Physiol 330(3):G280\u2013G292. https:\/\/doi.org\/10.1152\/ajpgi.00354.2025","journal-title":"Am J Physiol Gastrointest Liver Physiol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06228-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-06228-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06228-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:06:33Z","timestamp":1790611593000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-06228-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":68,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6228"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-06228-6","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"25 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"933"}}