{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:17:21Z","timestamp":1777396641126,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"s2","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,5,7]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Older adults presenting with dual-decline in cognition and walking speed face a 6-fold higher risk for dementia compared with those showing no decline. We hypothesized that the metabolomics profile of dual-decliners would be unique even before they show signs of decline in cognition and gait speed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of this study was to determine if plasma metabolomics signatures can discriminate dual-decliners from no decliners, purely cognitive decliners, and purely motor decliners prior to decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A retrospective cross-sectional study using baseline plasma for untargeted metabolomics analyses to investigate early signals of later dual-decline status in study participants (\n                      <jats:italic>n<\/jats:italic>\n                      \u200a=\u200a76) with convenient sampling. Dual-decline was operationalized as decline in gait speed (&gt;10\u200acm\/s) and cognition (&gt;2 points decline in Montreal Cognitive Assessment score) on at least two consecutive 6-monthly assessments. The participants\u2019 decliner status was evaluated 3 years after the blood sample was collected. Pair-wise comparison of detected compounds was completed using principal components and hierarchical clustering analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Analyses did not detect any cluster separation in untargeted metabolomes across baseline groups. However, follow-up analyses of specific molecules detected 4 compounds (17-Hydroxy-12-(hydroxymethyl)-10-oxo-8 oxapentacyclomethyl hexopyranoside, Fleroxacin, Oleic acid, and 5xi-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid) were at significantly higher concentration among the dual-decliners compared to non-decliners. The pure cognitive decliner group had significantly lower concentration of six compounds (1,3-nonanediol acetate, 4-(2-carboxyethyl)-2-methoxyphenyl beta-D-glucopyranosiduronic acid, oleic acid, 2E-3-[4-(sulfo-oxy)phenyl] acrylic acid, palmitelaidic acid, and myristoleic acid) compared to the non-decliner group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The unique metabolomics profile of dual-decliners warrants follow-up metabolomics analysis. Results may point to modifiable pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230683","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T11:05:48Z","timestamp":1695985548000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["A Metabolomics Analysis of a Novel Phenotype of Older Adults at Higher Risk of Dementia"],"prefix":"10.1177","volume":"99","author":[{"given":"Munira","family":"Sultana","sequence":"first","affiliation":[{"name":"Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Camicioli","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger A.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Psychology Science, University of Alberta, Edmonton, AB, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederico","family":"Pieruccini-Faria","sequence":"additional","affiliation":[{"name":"Gait and Brain Lab, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniy","family":"Petrotchenko","sequence":"additional","affiliation":[{"name":"Segal Cancer Proteomics Centre, Montreal, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Speechley","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph H.","family":"Borchers","sequence":"additional","affiliation":[{"name":"Segal Cancer Proteomics Centre, Montreal, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Montero-Odasso","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Western University, London, ON, Canada"},{"name":"Department of Medicine, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,5]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/alz.12068","article-title":"Alzheimer\u2019s Association Report: 2020 Alzheimer\u2019s disease facts and figures","volume":"16","author":"Alzheimer\u2019s Association","year":"2020","unstructured":"Alzheimer\u2019s Association (2020) Alzheimer\u2019s Association Report: 2020 Alzheimer\u2019s disease facts and figures. 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