{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:51:59Z","timestamp":1792651919806,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Previous research has suggested a link between the onset of Alzheimer\u2019s disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using <jats:italic>t<\/jats:italic>-tests or Wilcoxon rank-sum tests, with <jats:italic>p<\/jats:italic>-values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR &amp;lt; 0.05 and fold change (FC) &amp;gt; 1.5 or &amp;lt; 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP &amp;gt; 1 and FDR &amp;lt; 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1511437","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:49:03Z","timestamp":1734504543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted plasma metabolomics reveals potential biomarkers of the elderly with mild cognitive impairment in Qingdao rural area"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuchi","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxue","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1194\/jlr.R900011-JLR200","article-title":"Bile acids: Regulation of apoptosis by ursodeoxycholic acid.","volume":"50","author":"Amaral","year":"2009","journal-title":"J. Lipid. Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1237469","article-title":"Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation.","volume":"15","author":"Aquilani","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.3233\/jad-170742","article-title":"Associations of dietary protein and fiber intake with brain and blood Amyloid-\u03b2.","volume":"61","author":"Fernando","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B4","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1001\/jama.1983.03330450047024","article-title":"Association between nutritional status and cognitive functioning in a healthy elderly population.","volume":"249","author":"Goodwin","year":"1983","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1021\/ac303163f","article-title":"Investigation of the human brain metabolome to identify potential markers for early diagnosis and therapeutic targets of Alzheimer\u2019s disease.","volume":"85","author":"Graham","year":"2013","journal-title":"Anal. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1007\/s00018-013-1539-2","article-title":"Regulation of pyruvate metabolism and human disease.","volume":"71","author":"Gray","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/nrg.2017.63","article-title":"Human genetic variation and the gut microbiome in disease.","volume":"18","author":"Hall","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/sim.4780090710","article-title":"More powerful procedures for multiple significance testing.","volume":"9","author":"Hochberg","year":"1990","journal-title":"Stat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.clnu.2021.12.039","article-title":"Association of plasma uric acid levels with cognitive function among non-hyperuricemia adults: A prospective study.","volume":"41","author":"Huang","year":"2022","journal-title":"Clin. Nutr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neurobiolaging.2019.10.014","article-title":"Brain and blood metabolome for Alzheimer\u2019s dementia: Findings from a targeted metabolomics analysis.","volume":"86","author":"Huo","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1040476","article-title":"Decreased circulating branched-chain amino acids are associated with development of Alzheimer\u2019s disease in elderly individuals with mild cognitive impairment.","volume":"9","author":"Ikeuchi","year":"2022","journal-title":"Front. Nutr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e661","DOI":"10.1016\/s2468-2667(20)30185-7","article-title":"Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: A cross-sectional study.","volume":"5","author":"Jia","year":"2020","journal-title":"Lancet Public Health"},{"key":"B13","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond biomarkers and towards mechanisms.","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000012755","article-title":"Bone mineral loss and cognitive impairment: The PRESENT project.","volume":"97","author":"Kang","year":"2018","journal-title":"Medicine"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0467-5","article-title":"Non-alcoholic fatty liver disease induces signs of Alzheimer\u2019s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model.","volume":"13","author":"Kim","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1093\/ajcn\/65.1.20","article-title":"Nutritional status and cognitive functioning in a normally aging sample: A 6-y reassessment.","volume":"65","author":"La Rue","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310444","article-title":"\u03b1-Aminobutyric acid constrains macrophage-associated inflammatory diseases through metabolic reprogramming and epigenetic modification.","volume":"24","author":"Li","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2174\/1871524915666141216161246","article-title":"Plasma metabolic profiling of mild cognitive impairment and Alzheimer\u2019s disease using liquid chromatography\/mass spectrometry.","volume":"14","author":"Liu","year":"2014","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-023-05044-9","article-title":"The changes in metabolomics profile induced by intermittent theta burst stimulation in major depressive disorder: An exploratory study.","volume":"23","author":"Luo","year":"2023","journal-title":"BMC Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101129","article-title":"Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing.","volume":"4","author":"Lv","year":"2023","journal-title":"Cell Rep. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jalz.2018.07.217","article-title":"Altered bile acid profile associates with cognitive impairment in Alzheimer\u2019s disease-An emerging role for gut microbiome.","volume":"15","author":"MahmoudianDehkordi","year":"2019","journal-title":"Alzheimers Dement."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.828476","article-title":"The influence of serum uric acid on the brain and cognitive dysfunction.","volume":"13","author":"Mijailovic","year":"2022","journal-title":"Front. Psychiatry"},{"key":"B23","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":"B24","first-page":"581","article-title":"Dietary intakes and nutritional status of old people with dementia living at home in Oslo.","volume":"42","author":"Nes","year":"1988","journal-title":"Eur. J. Clin. Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: Metabolomics: the apogee of the omics trilogy.","volume":"13","author":"Patti","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/genes13111967","article-title":"Integrated analysis of the fecal metagenome and metabolome in bladder cancer in a Chinese population.","volume":"13","author":"Qin","year":"2022","journal-title":"Genes"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2022-100751","article-title":"The China alzheimer report 2022.","volume":"35","author":"Ren","year":"2022","journal-title":"Gen. Psychiatr."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062973","article-title":"Tryptophan metabolism and gut-brain homeostasis.","volume":"22","author":"Roth","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1097\/wad.0000000000000274","article-title":"Nutritional status is associated with severe dementia and mortality: The cache county dementia progression study.","volume":"32","author":"Sanders","year":"2018","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1194\/jlr.M022376","article-title":"Identification of a new plasma biomarker of Alzheimer\u2019s disease using metabolomics technology.","volume":"53","author":"Sato","year":"2012","journal-title":"J. Lipid Res."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2021.104911","article-title":"rMisbeta: A robust missing value imputation approach in transcriptomics and metabolomics data.","volume":"138","author":"Shahjaman","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1038\/ng.3916","article-title":"Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer\u2019s disease.","volume":"49","author":"Sims","year":"2017","journal-title":"Nat. Genet."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/nu10080975","article-title":"Uric acid and cognitive function in older individuals.","volume":"10","author":"Tana","year":"2018","journal-title":"Nutrients"},{"key":"B34","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1017\/s0033291700009119","article-title":"Tryptophan and nutritional status of patients with senile dementia.","volume":"16","author":"Thomas","year":"1986","journal-title":"Psychol. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.jalz.2018.01.003","article-title":"Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer\u2019s disease: A prospective study in eight cohorts.","volume":"14","author":"Tynkkynen","year":"2018","journal-title":"Alzheimers Dement."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1273807","article-title":"Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer\u2019s disease.","volume":"15","author":"Wang","year":"","journal-title":"Front. Aging Neurosci."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01324-4","article-title":"Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer\u2019s disease: Findings based on urine proteomics and machine learning.","volume":"15","author":"Wang","year":"","journal-title":"Alzheimers Res. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/s12264-012-1272-0","article-title":"Metabolomics: A novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer\u2019s disease.","volume":"28","author":"Xu","year":"2012","journal-title":"Neurosci. Bull."},{"key":"B39","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/mp.2011.131","article-title":"Potential metabolite markers of schizophrenia.","volume":"18","author":"Yang","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02449-3","article-title":"Plasma metabolomic profiles of dementia: A prospective study of 110,655 participants in the UK Biobank.","volume":"20","author":"Zhang","year":"2022","journal-title":"BMC Med."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1511437\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:49:05Z","timestamp":1734504545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1511437\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":40,"alternative-id":["10.3389\/fnagi.2024.1511437"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2024.1511437","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"article-number":"1511437"}}