{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:39:14Z","timestamp":1791819554023,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To compare the fecal levels of short\u2010chain fatty acids (SCFAs) in patients with mild cognitive impairment (MCI) and normal controls (NCs) and to examine whether fecal SCFAs could be used as the biomarker for the identification of patients with MCI. To examine the relationship between fecal SCFAs and amyloid\u2010\u03b2 (A\u03b2) deposition in the brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cohort of 32 MCI patients, 23 Parkinson's disease (PD) patients, and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini\u2010Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0\u20134) was measured by structural MRI. A\u03b2 positron emission tomography with\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010florbetapir (FBP) was performed in seven MCI patients at the time of stool sampling and in 28 MCI patients at an average of 12.3\u2009\u00b1\u20090.4\u2009months from the time of stool sampling to detect and quantify A\u03b2 deposition in the brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001, 95% CI: 0.628\u20130.876), specificity of 66.7%, and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid, and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 60% of participants into training dataset and 40% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 61.5% (8 in 13) of patients with MCI, and 72.7% (8 in 11) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with A\u03b2 deposition in cognition\u2010related brain regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reductions in fecal SCFAs were observed in patients with MCI compared with NC. Reduced fecal SCFAs were negatively associated with A\u03b2 deposition in cognition\u2010related brain regions in MCI group. Our findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14252","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T05:59:48Z","timestamp":1683266388000},"page":"3657-3666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Early changes of fecal short\u2010chain fatty acid levels in patients with mild cognitive impairments"],"prefix":"10.1111","volume":"29","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6242-1025","authenticated-orcid":false,"given":"Shengdi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Lab for Translational Research of Neurodegenerative Diseases, Shanghai Institute for Advanced Immunochemical Studies (SIAIS) Shanghai Tech University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0532-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00323-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02286-z"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.07.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317431"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190120"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110080"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59826"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.1215"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.07.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(88)90034-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.024"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/43.9.1657"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013225"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29063"},{"key":"e_1_2_10_21_1","first-page":"62, 65","article-title":"Mild cognitive impairment. When is it a precursor to Alzheimer's disease?","volume":"55","author":"Shah Y","year":"2000","journal-title":"Geriatrics"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2003.00118.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0325-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00361-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1177"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00315-z"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00296-z"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.018"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1528-y"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmz004"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800100-4.00003-9"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00025"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4611"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05895.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c02807"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2018.1400909"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00137"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858412440596"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01599-x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5151-1"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/NPT.0b013e3182462ea6"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2018.00765"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T06:36:44Z","timestamp":1697524604000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/cns.14252"],"URL":"https:\/\/doi.org\/10.1111\/cns.14252","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]},"assertion":[{"value":"2023-01-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}