{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:03:22Z","timestamp":1784034202591,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The global prevalence of dementia is significantly increasing. Early detection and prevention strategies, particularly for mild cognitive impairment (MCI), are crucial but currently hindered by the lack of established biomarkers. Here, we aimed to develop a high-precision screening method for MCI by combining D-amino acid profiles from peripheral blood samples with noninvasive subject information using nonlinear machine learning (ML) algorithms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A cross-sectional study was conducted with 200 participants aged 50\u201389 years, classified into cognitively normal and MCI-suspected groups based on Mini-Mental State Examination scores. High-throughput techniques were used to analyze the D-amino acid profiles, specifically D-alanine (%) and D-proline (%), in peripheral blood. Correlation analysis was performed between D-amino acid levels in venous and fingertip blood. The predictive performance of various ML models, including Logistic Regression, Random Forest, kernel Support Vector Machine (SVM), and Artificial Neural Network (ANN), was compared.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nonlinear models (kernel SVM and ANN) that combined D-amino acid profiles with subject information achieved the highest area under the curve values of 0.78 and 0.79, respectively, demonstrating that the combination of D-amino acid profiles and noninvasive subject information is effective in detecting MCI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Combining D-amino acid profiles with noninvasive subject information using nonlinear ML models, particularly kernel SVM and ANN, shows promise as a high-precision screening tool for MCI. This approach could serve as a cost-effective preliminary screening method before more invasive and expensive diagnostic tests and significantly contribute to the early detection and development of intervention strategies for dementia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf016","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T08:11:01Z","timestamp":1742026261000},"source":"Crossref","is-referenced-by-count":2,"title":["Examination of the relationship between D-amino acid profiles and cognitive function in individuals with mild cognitive impairment: a machine learning approach"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6167-0362","authenticated-orcid":false,"given":"Sou","family":"Sugiki","sequence":"first","affiliation":[{"name":"Human Health Care Products Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-0941","authenticated-orcid":false,"given":"Shigeki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Analytical Science Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Kimura","sequence":"additional","affiliation":[{"name":"Analytical Science Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Katada","sequence":"additional","affiliation":[{"name":"Human Health Care Products Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Misawa","sequence":"additional","affiliation":[{"name":"Human Health Care Products Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Tsujimura","sequence":"additional","affiliation":[{"name":"Analytical Science Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Hibi","sequence":"additional","affiliation":[{"name":"Human Health Care Products Research, Kao Corporation , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"2025042204015980100_CIT0001","volume-title":"Global Status Report on the Public Health Response to Dementia","author":"World Health Organization","year":"2021"},{"key":"2025042204015980100_CIT0002","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1017\/ipm.2018.4","article-title":"The Lancet Commission on dementia prevention, intervention, and care: a call for action","volume":"36","author":"Orgeta","year":"2019","journal-title":"Ir J Psychol Med."},{"key":"2025042204015980100_CIT0003","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1017\/s1041610204000092","article-title":"Is MCI really just early dementia? A systematic review of conversion studies","volume":"16","author":"Bruscoli","year":"2004","journal-title":"Int Psychogeriatr."},{"key":"2025042204015980100_CIT0004","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/ana.21326","article-title":"Frequency and course of mild cognitive impairment in a multiethnic community","volume":"63","author":"Manly","year":"2008","journal-title":"Ann Neurol."},{"key":"2025042204015980100_CIT0005","doi-asserted-by":"publisher","first-page":"73","DOI":"10.4103\/1673-5374.286957","article-title":"Application of modern neuroimaging technology in the diagnosis and study of Alzheimer\u2019s disease","volume":"16","author":"Zeng","year":"2021","journal-title":"Neural Regen Res"},{"key":"2025042204015980100_CIT0006","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/jpm10030116","article-title":"Significance of blood and cerebrospinal fluid biomarkers for Alzheimer\u2019s disease: sensitivity, specificity and potential for clinical use","volume":"10","author":"d\u2019Abramo","year":"2020","journal-title":"J Pers Med."},{"key":"2025042204015980100_CIT0007","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/mp.2013.40","article-title":"A blood-based predictor for neocortical Abeta burden in Alzheimer\u2019s disease: results from the AIBL study","volume":"19","author":"Burnham","year":"2014","journal-title":"Mol Psychiatry."},{"key":"2025042204015980100_CIT0008","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1001\/jamaneurol.2020.4201","article-title":"Associations of plasma phospho-tau217 levels with tau positron emission tomography in early Alzheimer disease","volume":"78","author":"Janelidze","year":"2021","journal-title":"JAMA Neurol."},{"key":"2025042204015980100_CIT0009","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1001\/jamaneurol.2021.3180","article-title":"Head-to-head comparison of 8 plasma amyloid-beta 42\/40 assays in Alzheimer disease","volume":"78","author":"Janelidze","year":"2021","journal-title":"JAMA Neurol."},{"key":"2025042204015980100_CIT0010","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13195-023-01296-5","article-title":"Performance of plasma Abeta42\/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status","volume":"15","author":"Bun","year":"2023","journal-title":"Alzheimers Res Ther."},{"key":"2025042204015980100_CIT0011","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature25456","article-title":"High performance plasma amyloid-beta biomarkers for Alzheimer\u2019s disease","volume":"554","author":"Nakamura","year":"2018","journal-title":"Nature."},{"key":"2025042204015980100_CIT0012","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.dadm.2015.04.003","article-title":"Amyloid-beta sequester proteins as blood-based biomarkers of cognitive decline","volume":"1","author":"Uchida","year":"2015","journal-title":"Alzheimers Dement (Amst)"},{"key":"2025042204015980100_CIT0013","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.3390\/nu11092205","article-title":"D-amino acids in health and disease: a focus on cancer","volume":"11","author":"Bastings","year":"2019","journal-title":"Nutrients."},{"key":"2025042204015980100_CIT0014","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.bbapap.2018.03.001","article-title":"D-Amino acids in protein: the mirror of life as a molecular index of aging","volume":"1866","author":"Fujii","year":"2018","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"2025042204015980100_CIT0015","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/s41598-020-57878-y","article-title":"Development of a cognitive function marker based on D-amino acid proportions using new chiral tandem LC-MS\/MS systems","volume":"10","author":"Kimura","year":"2020","journal-title":"Sci Rep."},{"key":"2025042204015980100_CIT0016","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.pnpbp.2003.11.009","article-title":"Possible role of D-serine in the pathophysiology of Alzheimer\u2019s disease","volume":"28","author":"Hashimoto","year":"2004","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry."},{"key":"2025042204015980100_CIT0017","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41398-021-01202-3","article-title":"Serum D-serine levels are altered in early phases of Alzheimer\u2019s disease: towards a precocious biomarker","volume":"11","author":"Piubelli","year":"2021","journal-title":"Transl Psychiatry."},{"key":"2025042204015980100_CIT0018","doi-asserted-by":"publisher","first-page":"140537","DOI":"10.1016\/j.bbapap.2020.140537","article-title":"Cerebrospinal fluid and serum d-serine concentrations are unaltered across the whole clinical spectrum of Alzheimer\u2019s disease","volume":"1868","author":"Nuzzo","year":"2020","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"2025042204015980100_CIT0019","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state.\u201d A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res."},{"key":"2025042204015980100_CIT0020","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/a:1010933404324","article-title":"Random forest","volume":"45","author":"Leo","year":"2001","journal-title":"Mach Learn."},{"key":"2025042204015980100_CIT0021","first-page":"821","article-title":"Theoretical foundations of the potential function method in pattern recognition learning","volume":"25","author":"Aizerman","year":"1964","journal-title":"Autom Remote Control."},{"key":"2025042204015980100_CIT0022","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/323533a0","article-title":"Learning representations by back-propagating errors","volume":"323","author":"Rumelhart","year":"1986","journal-title":"Nature."},{"key":"2025042204015980100_CIT0023","doi-asserted-by":"publisher","first-page":"CD010783","DOI":"10.1002\/14651858.CD010783.pub2","article-title":"Mini-Mental State Examination (MMSE) for the detection of Alzheimer\u2019s disease and other dementias in people with mild cognitive impairment (MCI)","volume":"2015","author":"Arevalo-Rodriguez","year":"2015","journal-title":"Cochrane Database Syst Rev."},{"key":"2025042204015980100_CIT0024","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.2174\/0929867328666211125092438","article-title":"D-amino acids as novel blood-based biomarkers","volume":"29","author":"Murtas","year":"2022","journal-title":"Curr Med Chem."},{"key":"2025042204015980100_CIT0025","doi-asserted-by":"publisher","first-page":"172760","DOI":"10.1016\/j.pbb.2019.172760","article-title":"D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer\u2019s disease or mild cognitive impairment","volume":"185","author":"Lin","year":"2019","journal-title":"Pharmacol Biochem Behav."},{"key":"2025042204015980100_CIT0026","doi-asserted-by":"publisher","first-page":"3737","DOI":"10.1016\/j.xphs.2019.08.026","article-title":"Overall similarities and a possible factor affecting plasma metabolome profiles between venous and capillary blood samples from 20 healthy human males","volume":"108","author":"Saito","year":"2019","journal-title":"J Pharm Sci."},{"key":"2025042204015980100_CIT0027","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1007\/s11064-020-03014-1","article-title":"D-Serine, the shape-shifting NMDA receptor Co-agonist","volume":"45","author":"Coyle","year":"2020","journal-title":"Neurochem Res."},{"key":"2025042204015980100_CIT0028","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1016\/j.molmed.2023.09.001","article-title":"d-Amino acids: new clinical pathways for brain diseases","volume":"29","author":"Souza","year":"2023","journal-title":"Trends Mol Med."},{"key":"2025042204015980100_CIT0029","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1162\/neco_a_01486","article-title":"Comparison of the representational power of random forests, binary decision diagrams, and neural networks","volume":"34","author":"Kumano","year":"2022","journal-title":"Neural Comput."},{"key":"2025042204015980100_CIT0030","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1002\/alz.12662","article-title":"Consideration of sex and gender in Alzheimer\u2019s disease and related disorders from a global perspective","volume":"18","author":"Mielke","year":"2022","journal-title":"Alzheimers Dement"},{"key":"2025042204015980100_CIT0031","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1016\/j.jalz.2014.12.007","article-title":"Alzheimer\u2019s disease first symptoms are age dependent: Evidence from the NACC dataset","volume":"11","author":"Barnes","year":"2015","journal-title":"Alzheimers Dement"},{"key":"2025042204015980100_CIT0032","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1093\/arclin\/acad009","article-title":"Linear and nonlinear effect of years of schooling, sex, and age on the CERAD-MX and complementary tasks in a Mexican sample: a cross-sectional study","volume":"38","author":"Zuno Reyes","year":"2023","journal-title":"Arch Clin Neuropsychol."},{"key":"2025042204015980100_CIT0033","doi-asserted-by":"publisher","first-page":"5406196","DOI":"10.1155\/2022\/5406196","article-title":"Coresidence of older parents and adult children increases older adults\u2019 self-reported psychological well-being","volume":"2022","author":"Lee","year":"2022","journal-title":"Int J Alzheimers Dis."},{"key":"2025042204015980100_CIT0034","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s11011-014-9501-z","article-title":"Obesity as a risk factor for Alzheimer\u2019s disease: the role of adipocytokines","volume":"29","author":"Letra","year":"2014","journal-title":"Metab Brain Dis."}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ijnp\/advance-article-pdf\/doi\/10.1093\/ijnp\/pyaf016\/62417267\/pyaf016.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/28\/4\/pyaf016\/62417267\/pyaf016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/28\/4\/pyaf016\/62417267\/pyaf016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T08:02:11Z","timestamp":1745308931000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/doi\/10.1093\/ijnp\/pyaf016\/8078914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,15]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/ijnp\/pyaf016","relation":{},"ISSN":["1461-1457","1469-5111"],"issn-type":[{"value":"1461-1457","type":"print"},{"value":"1469-5111","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,3,15]]},"article-number":"pyaf016"}}