{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:54:59Z","timestamp":1791302099879,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23AG047978"],"award-info":[{"award-number":["K23AG047978"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK035816"],"award-info":[{"award-number":["P30DK035816"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD021562"],"award-info":[{"award-number":["S10OD021562"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Affairs Medical Center","award":["K23AG047978"],"award-info":[{"award-number":["K23AG047978"]}]},{"name":"Veterans Affairs Medical Center","award":["P30DK035816"],"award-info":[{"award-number":["P30DK035816"]}]},{"name":"Veterans Affairs Medical Center","award":["S10OD021562"],"award-info":[{"award-number":["S10OD021562"]}]},{"name":"Chair of Medicine Scholars Award from the University of Washington School of Medicine","award":["K23AG047978"],"award-info":[{"award-number":["K23AG047978"]}]},{"name":"Chair of Medicine Scholars Award from the University of Washington School of Medicine","award":["P30DK035816"],"award-info":[{"award-number":["P30DK035816"]}]},{"name":"Chair of Medicine Scholars Award from the University of Washington School of Medicine","award":["S10OD021562"],"award-info":[{"award-number":["S10OD021562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Brain glucose hypometabolism is an early sign of Alzheimer\u2019s disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a pilot study of older adults who underwent saline and triglyceride (TG) infusions. Older adults (12 cognitively normal (CN), age 65.3 \u00b1 8.1, and 9 with cognitive impairment (CI), age 70.9 \u00b1 8.6) underwent a 5 h TG or saline infusion on different days using a random crossover design; CSF was collected at the end of infusion. Aqueous metabolites were measured using a targeted mass spectroscopy (MS) platform focusing on 215 metabolites from over 35 different metabolic pathways. Data were analyzed using MetaboAnalyst 4.0 and SAS. Of the 215 targeted metabolites, 99 were detectable in CSF. Only one metabolite significantly differed by treatment: the ketone body 3-hydroxybutyrate (HBA). Post hoc analyses showed that HBA levels were associated with age and markers of metabolic syndrome and demonstrated different correlation patterns for the two treatments. When analyzed by cognitive diagnosis group, TG-induced increases in HBA were over 3 times higher for those with cognitive impairment (change score CN +9.8 uM \u00b1 8.3, CI +32.4 \u00b1 7.4, p = 0.0191). Interestingly, individuals with cognitive impairment had higher HBA levels after TG infusion than those with normal cognition. These results suggest that interventions that increase plasma ketones may lead to higher brain ketones in groups at risk for AD and should be confirmed in larger intervention studies.<\/jats:p>","DOI":"10.3390\/metabo13040569","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T05:51:41Z","timestamp":1681710701000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer\u2019s Disease and Mild Cognitive Impairment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-2916","authenticated-orcid":false,"given":"Angela J.","family":"Hanson","sequence":"first","affiliation":[{"name":"Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Banks","sequence":"additional","affiliation":[{"name":"Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA"},{"name":"Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.","family":"Bettcher","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pepin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-8118","authenticated-orcid":false,"given":"Daniel","family":"Raftery","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-2486","authenticated-orcid":false,"given":"Sandi L.","family":"Navarro","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.3390\/ijerph6041335","article-title":"Dietary patterns associated with Alzheimer\u2019s disease: Population based study","volume":"6","year":"2009","journal-title":"Int. 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