Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia
Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data fro...
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| description | Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998–1999 (mean age = 75.2 ± 2.9 years old, 37.8% Black, 50% women) from the Health, Aging and Body Composition study. Dementia diagnosis was determined by race-specific decline in 3MS scores, medication use, and hospital records through 2014. Cognition and mobility were repeatedly measured using 3MS and a 20-m walking test up to 10 years, respectively. We examined metabolite associations with changes in 3MS (
n
= 2046) and gait speed (
n
= 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted
p
|
| doi_str_mv | 10.1007/s11357-024-01228-7 |
| format | Article |
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n
= 2046) and gait speed (
n
= 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted
p
< 0.05). Twenty-six metabolites were associated with both cognitive and gait declines. Eighteen of 26 metabolites were associated with dementia risk (
p
< 0.05), notably amino acids, glycerophospholipids (lysoPCs, PCs, PEs), and sphingolipids. Results remained similar after adjusting for cardiovascular disease or apolipoprotein E ɛ4 carrier status. During aging, metabolomic profiles of cognitive decline and mobility decline show distinct and shared signatures. Shared metabolomic profiles suggest that inflammation and deficits in mitochondria and the urea cycle in addition to the central nervous system may play key roles in both cognitive and mobility declines and predict dementia. Future studies are warranted to investigate longitudinal metabolite changes and metabolomic markers with dementia pathologies.</description><identifier>ISSN: 2509-2723</identifier><identifier>ISSN: 2509-2715</identifier><identifier>EISSN: 2509-2723</identifier><identifier>DOI: 10.1007/s11357-024-01228-7</identifier><identifier>PMID: 38829458</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Apolipoprotein E ; Biomarkers - blood ; Biomedical and Life Sciences ; Body composition ; Cardiovascular diseases ; Cell Biology ; Central nervous system ; Cognition & reasoning ; Cognitive ability ; Cognitive Dysfunction - blood ; Dementia ; Dementia - blood ; Dementia disorders ; Female ; Gait ; Geriatrics/Gerontology ; Humans ; Life Sciences ; Male ; Metabolites ; Metabolome ; Metabolomics ; Mobility ; Mobility Limitation ; Molecular Medicine ; Original ; Original Article ; Risk Factors ; Sphingolipids</subject><ispartof>GeroScience, 2024-06, Vol.46 (5), p.4883-4894</ispartof><rights>This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024</rights><rights>2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.</rights><rights>This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-5f32e0eff36c62b57f2d211c4c19557eb570c385ea561ed7297e570a57d1c1e43</cites><orcidid>0000-0003-2706-1439</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336156/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336156/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38829458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Qu</creatorcontrib><creatorcontrib>Yao, Shanshan</creatorcontrib><creatorcontrib>Marron, Megan M.</creatorcontrib><creatorcontrib>Greig, Erin E.</creatorcontrib><creatorcontrib>Shore, Supriya</creatorcontrib><creatorcontrib>Ferrucci, Luigi</creatorcontrib><creatorcontrib>Shah, Ravi</creatorcontrib><creatorcontrib>Murthy, Venkatesh L.</creatorcontrib><creatorcontrib>Newman, Anne B.</creatorcontrib><title>Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia</title><title>GeroScience</title><addtitle>GeroScience</addtitle><addtitle>Geroscience</addtitle><description>Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998–1999 (mean age = 75.2 ± 2.9 years old, 37.8% Black, 50% women) from the Health, Aging and Body Composition study. Dementia diagnosis was determined by race-specific decline in 3MS scores, medication use, and hospital records through 2014. Cognition and mobility were repeatedly measured using 3MS and a 20-m walking test up to 10 years, respectively. We examined metabolite associations with changes in 3MS (
n
= 2046) and gait speed (
n
= 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted
p
< 0.05). Twenty-six metabolites were associated with both cognitive and gait declines. Eighteen of 26 metabolites were associated with dementia risk (
p
< 0.05), notably amino acids, glycerophospholipids (lysoPCs, PCs, PEs), and sphingolipids. Results remained similar after adjusting for cardiovascular disease or apolipoprotein E ɛ4 carrier status. During aging, metabolomic profiles of cognitive decline and mobility decline show distinct and shared signatures. Shared metabolomic profiles suggest that inflammation and deficits in mitochondria and the urea cycle in addition to the central nervous system may play key roles in both cognitive and mobility declines and predict dementia. Future studies are warranted to investigate longitudinal metabolite changes and metabolomic markers with dementia pathologies.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Apolipoprotein E</subject><subject>Biomarkers - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Body composition</subject><subject>Cardiovascular diseases</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Cognition & reasoning</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - blood</subject><subject>Dementia</subject><subject>Dementia - blood</subject><subject>Dementia disorders</subject><subject>Female</subject><subject>Gait</subject><subject>Geriatrics/Gerontology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Metabolites</subject><subject>Metabolome</subject><subject>Metabolomics</subject><subject>Mobility</subject><subject>Mobility Limitation</subject><subject>Molecular Medicine</subject><subject>Original</subject><subject>Original Article</subject><subject>Risk Factors</subject><subject>Sphingolipids</subject><issn>2509-2723</issn><issn>2509-2715</issn><issn>2509-2723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kU9PHSEUxYmpqUb9Al0Ykm66GeXCADOrpjH1T2LiwnbXhPCYyxPDDK8wY-K3L_VZtV10BTn3d8_lcgj5AOwEGNOnBUBI3TDeNgw47xq9Q_a5ZH3DNRfv3tz3yFEp94wx0EoJxt6TPdF1vG9lt09-3N7ZjAPdRFtGS0ec7SrFNAZHNzn5ELHQ5KlL6ynM4QGpnQY6plWIYX6kA7oYJqwoDsHN1C_zkrHKI05zsIdk19tY8Oj5PCDfz79-O7tsrm8urs6-XDdOSDU30guODL0Xyim-ktrzgQO41kEvpcaqMCc6iVYqwEHzXmOVrNQDOMBWHJDPW9_NshpxcHV4ttFschhtfjTJBvN3ZQp3Zp0eTP1DoUCq6vDp2SGnnwuW2YyhOIzRTpiWYgRTLbQcJK_ox3_Q-7Tkqe5XqV6CZEJCpfiWcjmVktG_vAaY-R2g2QZoaoDmKUCja9Px2z1eWv7EVQGxBUotTWvMr7P_Y_sL6o6nGg</recordid><startdate>20240603</startdate><enddate>20240603</enddate><creator>Tian, Qu</creator><creator>Yao, Shanshan</creator><creator>Marron, Megan M.</creator><creator>Greig, Erin E.</creator><creator>Shore, Supriya</creator><creator>Ferrucci, Luigi</creator><creator>Shah, Ravi</creator><creator>Murthy, Venkatesh L.</creator><creator>Newman, Anne B.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2706-1439</orcidid></search><sort><creationdate>20240603</creationdate><title>Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia</title><author>Tian, Qu ; 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Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998–1999 (mean age = 75.2 ± 2.9 years old, 37.8% Black, 50% women) from the Health, Aging and Body Composition study. Dementia diagnosis was determined by race-specific decline in 3MS scores, medication use, and hospital records through 2014. Cognition and mobility were repeatedly measured using 3MS and a 20-m walking test up to 10 years, respectively. We examined metabolite associations with changes in 3MS (
n
= 2046) and gait speed (
n
= 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted
p
< 0.05). Twenty-six metabolites were associated with both cognitive and gait declines. Eighteen of 26 metabolites were associated with dementia risk (
p
< 0.05), notably amino acids, glycerophospholipids (lysoPCs, PCs, PEs), and sphingolipids. Results remained similar after adjusting for cardiovascular disease or apolipoprotein E ɛ4 carrier status. During aging, metabolomic profiles of cognitive decline and mobility decline show distinct and shared signatures. Shared metabolomic profiles suggest that inflammation and deficits in mitochondria and the urea cycle in addition to the central nervous system may play key roles in both cognitive and mobility declines and predict dementia. Future studies are warranted to investigate longitudinal metabolite changes and metabolomic markers with dementia pathologies.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>38829458</pmid><doi>10.1007/s11357-024-01228-7</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-2706-1439</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Aging Apolipoprotein E Biomarkers - blood Biomedical and Life Sciences Body composition Cardiovascular diseases Cell Biology Central nervous system Cognition & reasoning Cognitive ability Cognitive Dysfunction - blood Dementia Dementia - blood Dementia disorders Female Gait Geriatrics/Gerontology Humans Life Sciences Male Metabolites Metabolome Metabolomics Mobility Mobility Limitation Molecular Medicine Original Original Article Risk Factors Sphingolipids |
| title | Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia |
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