{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:03:05Z","timestamp":1790784185102,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG081426"],"award-info":[{"award-number":["R01AG081426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1RF1AG079100\u201001A1"],"award-info":[{"award-number":["1RF1AG079100\u201001A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Plasma high\u2010density lipoprotein (HDL) varies in size. We examined the associations between HDL subclasses and their lipid composition and incident dementia risk\u00a0in older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We included 23,790 United Kingdom (UK) Biobank (UKB) and 147 Atherosclerosis Risk in Communities (ARIC) older adults free of dementia at baseline. HDL subclasses and their lipid composition were characterized using two distinct approaches: Nightingale nuclear magnetic resonance (NMR) spectroscopy in UKB and anion\u2010exchange chromatography followed by mass spectrometry\u2010based lipidomics of physically isolated HDL subfractions (AEX\u2010MS) in ARIC. Cox regression models were used to evaluate the associations, adjusting for covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In the UKB, Nightingale NMR\u2010derived plasma small and very large HDL particle and six lipid concentrations (total lipids, triglycerides [TG], phospholipids, free cholesterol, cholesterol ester [CE], total cholesterol) were associated with lower and higher risks of incident dementia, respectively. These associations were likely driven mainly by particle concentration in NMR\u2010derived small HDL and by both lipid and lipid concentrations in NMR\u2010derived very large HDL. In the ARIC, total TG in AEX\u2010defined HDL subfraction 1 (e.g., smaller HDL), total lysophosphatidylcholine (LPC) and phosphatidylethanolamine (PE), and TG in AEX\u2010defined subfraction 2 (e.g., larger HDL) were associated with a lower incident dementia risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Although different HDL subclass characterization and lipid measurement methods made it difficult to compare results across cohorts, HDL subclasses and their lipid compositions were associated with the risk of incident dementia in both cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71893","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:16:44Z","timestamp":1790781404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of plasma HDL subclasses with incident dementia risk\u00a0in older adults"],"prefix":"10.1002","volume":"22","author":[{"given":"Binchong","family":"An","sequence":"first","affiliation":[{"name":"Department of Lab Medicine and Pathology University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Lab Medicine and Pathology University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Lab Medicine and Pathology University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Roemhild","sequence":"additional","affiliation":[{"name":"Department of Lab Medicine and Pathology University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight R.","family":"Stoll","sequence":"additional","affiliation":[{"name":"Department of Chemistry Gustavus Adolphus College  St Peter Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L","family":"Lutsey","sequence":"additional","affiliation":[{"name":"School of Public Health University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M","family":"Mielke","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"Edson College of Nursing and Health Innovation Arizona State University  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron C","family":"Hoogeveen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Research Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science School of Public Health University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Alonso","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Rollins School of Public Health Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Lab Medicine and Pathology University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"3","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1111\/j.1582-4934.2009.00713.x","article-title":"Small, dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipoprotein A\u2010I","volume":"14","author":"De Souza JA","year":"2010","journal-title":"J Cell Mol Med"},{"issue":"7","key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1161\/CIRCRESAHA.116.305485","article-title":"HDL particle size is a critical determinant of ABCA1\u2010mediated macrophage cellular cholesterol export","volume":"116","author":"Du X\u2010M","year":"2015","journal-title":"Circ Res"},{"issue":"6","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1161\/CIRCRESAHA.116.308685","article-title":"Enhanced HDL functionality in small HDL species produced upon remodeling of HDL by reconstituted HDL, CSL112: effects on cholesterol efflux, anti\u2010inflammatory and antioxidative activity","volume":"119","author":"Didichenko SA","year":"2016","journal-title":"Circ Res"},{"issue":"1","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1194\/jlr.M076927","article-title":"Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine\u20101\u2010phosphate","volume":"59","author":"Persegol L","year":"2018","journal-title":"J Lipid Res"},{"issue":"2","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3233\/JAD-200291","article-title":"Plasma high density lipoprotein small subclass is reduced in Alzheimer's disease patients and correlates with cognitive performance","volume":"77","author":"Pedrini S","year":"2020","journal-title":"J Alzheimers Dis"},{"issue":"2","key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/alz.12649","article-title":"The small HDL particle hypothesis of Alzheimer's disease","volume":"19","author":"Martinez AE","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"5","key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1093\/cvr\/cvab164","article-title":"Plasma high\u2010density lipoprotein cholesterol and risk of dementia: observational and genetic studies","volume":"118","author":"Kjeldsen EW","year":"2022","journal-title":"Cardiovasc Res"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2023.100963"},{"issue":"11","key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1194\/jlr.R036095","article-title":"Unraveling the complexities of the HDL lipidome","volume":"54","author":"Kontush A","year":"2013","journal-title":"J Lipid Res"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm027"},{"issue":"12","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1001\/archneurol.2010.297","article-title":"Association of higher levels of high\u2010density lipoprotein cholesterol in elderly individuals and lower risk of late\u2010onset Alzheimer disease","volume":"67","author":"Reitz C","year":"2010","journal-title":"Arch Neurol"},{"issue":"1","key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41398-018-0336-y","article-title":"The association between midlife serum high\u2010density lipoprotein and mild cognitive impairment and dementia after 19 years of follow\u2010up","volume":"9","author":"Svensson T","year":"2019","journal-title":"Transl Psychiatry"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyab156"},{"issue":"1","key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1161\/CIRCGENETICS.114.000216","article-title":"Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics","volume":"8","author":"Soininen P","year":"2015","journal-title":"Circ Cardiovasc Genet"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.63033","article-title":"Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID\u201019 in the general population","volume":"10","author":"Julkunen H","year":"2021","journal-title":"elife"},{"issue":"9","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1093\/aje\/kwx016","article-title":"Quantitative serum nuclear magnetic resonance metabolomics in large\u2010scale epidemiology: a primer on\u2010omic technologies","volume":"186","author":"W\u00fcrtz P","year":"2017","journal-title":"Am J Epidemiol"},{"issue":"9","key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1039\/b910205a","article-title":"High\u2010throughput serum NMR metabonomics for cost\u2010effective holistic studies on systemic metabolism","volume":"134","author":"Soininen P","year":"2009","journal-title":"Analyst"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D300003\u2010JLR200"},{"issue":"3","key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1177\/13872877241305806","article-title":"The association of high\u2010density lipoprotein cargo proteins with brain volume in older adults in the atherosclerosis risk in communities (ARIC)","volume":"103","author":"Li D","year":"2025","journal-title":"J Alzheimers Dis"},{"issue":"6","key":"e_1_2_8_21_1","doi-asserted-by":"crossref","DOI":"10.1002\/pmic.202000224","article-title":"Characterization of human plasma lipoproteins using anion exchange fast protein liquid chromatography and targeted mass spectrometry assay","volume":"21","author":"Seidl C","year":"2021","journal-title":"Proteomics"},{"issue":"6","key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10654-019-00499-1","article-title":"Identifying dementia outcomes in UK Biobank: a validation study of primary care, hospital admissions and mortality data","volume":"34","author":"Wilkinson T","year":"2019","journal-title":"Eur J Epidemioly"},{"issue":"16","key":"e_1_2_8_23_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.025646","article-title":"Risk of dementia associated with atrial cardiopathy: the ARIC study","volume":"11","author":"Johansen MC","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"7","key":"e_1_2_8_24_1","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70365","article-title":"Associations between mid\u2010life social relationships and the risk of incident dementia: the ARIC study","volume":"21","author":"Groechel RC","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"2","key":"e_1_2_8_25_1","first-page":"e154","article-title":"Genetic risk, midlife life's simple 7, and incident dementia in the atherosclerosis risk in communities study","volume":"99","author":"Tin A","year":"2022","journal-title":"Neurology"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006\u2010341x.2001.00114.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.16302"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000207923"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010005\u20100030\u20104"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0021\u20109150(01)00447\u20106"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201005449\u2010z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000140818.00570.2d"},{"issue":"9","key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.bbalip.2013.06.004","article-title":"Aging affects high\u2010density lipoprotein composition and function","volume":"1831","author":"Holzer M","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20102144"},{"issue":"1","key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12944-025-02620-8","article-title":"High\u2010density lipoprotein particles are associated with the risk of mortality from all\u2010causes and cardiovascular diseases (CVDs) in patients with CVD: a systematic review and meta\u2010analysis study","volume":"24","author":"Sharifi\u2010Zahabi E","year":"2025","journal-title":"Lipids Health Dis"},{"issue":"3","key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1124\/jpet.118.254201","article-title":"Apolipoprotein AI crosses the blood\u2010brain barrier through clathrin\u2010independent and cholesterol\u2010mediated endocytosis","volume":"369","author":"Zhou AL","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"e_1_2_8_37_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.114.001156","article-title":"Intravenously injected human apolipoprotein A\u2010I rapidly enters the central nervous system via the choroid plexus","volume":"3","author":"Stukas S","year":"2014","journal-title":"J Am Heart Assoc"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010019\u20100497\u20109"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.127829"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fnins.2019.00419","article-title":"The extent of human apolipoprotein AI lipidation strongly affects the \u03b2\u2010amyloid efflux across the blood\u2010brain barrier in vitro","volume":"13","author":"Dal Magro R","year":"2019","journal-title":"Front Neurosci"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.17.6.1053"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12937\u2010024\u201000983\u20109"},{"issue":"1","key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12916-022-02449-3","article-title":"Plasma metabolomic profiles of dementia: a prospective study of 110,655 participants in the UK Biobank","volume":"20","author":"Zhang X","year":"2022","journal-title":"BMC medicine"},{"issue":"5","key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"e489","DOI":"10.1212\/WNL.0000000000207458","article-title":"Association of baseline metabolomic profiles with incident stroke and dementia and with imaging markers of cerebral small vessel disease","volume":"101","author":"Harshfield EL","year":"2023","journal-title":"Neurology"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71893","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71893","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:16:49Z","timestamp":1790781409000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/alz.71893"],"URL":"https:\/\/doi.org\/10.1002\/alz.71893","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"assertion":[{"value":"2026-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71893"}}