{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T08:06:40Z","timestamp":1768637200179,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>It is unclear whether inflammation, that is, high interleukin\u20106 (IL\u20106) levels, and genetic risk, that is, apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 allele, have a compounding effect on cognitive decline (CD).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We analyzed a subset of participants from the longitudinal cohort study, Chicago Health and Aging Project, comprising 1120 biracial community\u2010dwelling older adults (60% Black and 62% women), and mean follow\u2010up\u00a0=\u00a06.4 years. We ran adjusted mixed\u2010effects models on2 longitudinal CD.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In <jats:italic>APOE<\/jats:italic> \u03b54 carriers, higher serum IL\u20106 was not associated with the rate of CD (\u03b2\u00a0=\u00a0\u20130.0091 [standard deviation (SD)\u00a0=\u00a00.0165, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.5800]). Conversely, in non\u2010\u03b54 carriers, compared to the lower tertile, those with the upper tertile of serum IL\u20106 levels experienced significantly accelerated CD (\u03b2\u00a0=\u00a0\u20130.0257 [SD\u00a0=\u00a00.0084, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0023]).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Even without the largest genetic risk factor for late\u2010onset Alzheimer's disease\/Alzheimer's disease and related dementias (AD\/ADRD), elevated serum IL\u20106 still accelerate the rate of CD in non\u2010<jats:italic>APOE<\/jats:italic> \u03b54 carriers. Hence, interventions ameliorating inflammation may prevent AD\/ADRD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Interleukin\u20106 (IL\u20106) and the apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 allele have been separately associated with an increased risk for cognitive decline, but their interaction remains unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In \u03b54 carriers, IL\u20106 was not associated with cognitive decline. However, even without the biggest genetic risk factor for Alzheimer's disease (AD), that is, <jats:italic>APOE<\/jats:italic> \u03b54, elevated serum IL\u20106 still could confer accelerated rate of cognitive decline, with a detrimental effect half of that imposed by <jats:italic>APOE<\/jats:italic> \u03b54 alone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We found no racial differences in these associations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings contribute complementary evidence on non\u2013<jats:italic>APOE<\/jats:italic> \u03b54\u2010dependent and non\u2010AD biological pathways through which cognitive decline can still be accelerated in non\u2010<jats:italic>APOE<\/jats:italic> \u03b54 carriers and highlight a specific subgroup of older adults who are at a higher risk of AD and thus may benefit from anti\u2010inflammatory interventions.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70002","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T07:06:17Z","timestamp":1729494377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prospective associations of interleukin\u20106 and <i>APOE<\/i> allele with cognitive decline in biracial community\u2010dwelling older adults: The Chicago Health and Aging Project (CHAP)"],"prefix":"10.1002","volume":"16","author":[{"given":"Ted K. S.","family":"Ng","sequence":"first","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Beck","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaja","family":"Desai","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klodian","family":"Dhana","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Research Center Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis A.","family":"Evans","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumar B.","family":"Rajan","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA"},{"name":"Rush Alzheimer's Disease Research Center Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00571510"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23634"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2003.09.011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1037\/hea0000331"},{"issue":"2","key":"e_1_2_9_6_1","first-page":"1","article-title":"Interleukin\u20106 and chronic inflammation","volume":"8","author":"Gabay C","year":"2006","journal-title":"Arthritis Res Ther"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(96)00107-8"},{"key":"e_1_2_9_8_1","first-page":"1","article-title":"APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease","author":"Fortea J","year":"2024","journal-title":"Nat Med"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70325-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306923200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00754"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12362"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12589"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.06.3063"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.2.185"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2021.105339"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000665"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.3.371"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2003-5501"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25874"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)43176-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25228"},{"key":"e_1_2_9_23_1","unstructured":"IL\u20106 Assays.Quanterix. Published October 3 2023. Accessed March 18 2024.https:\/\/www.quanterix.com\/simoa\u2010assay\u2010kits\/il\u20106\/"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000083989.44027.05"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001774"},{"key":"e_1_2_9_26_1","unstructured":"R Core TeamR R: A language and environment for statistical computing. Published online 2013."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp198"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000263217.36439.da"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.08.012"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls187"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.13165"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.553998"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.4238"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000073620.42047.D7"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00313"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0298-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2004.07.240"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.01.035"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.064154"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0696-y"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2021.114191"}],"container-title":["Alzheimer's &amp; Dementia: Diagnosis, Assessment &amp; Disease Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dad2.70002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T18:45:14Z","timestamp":1760381114000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/dad2.70002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/dad2.70002"],"URL":"https:\/\/doi.org\/10.1002\/dad2.70002","archive":["Portico"],"relation":{},"ISSN":["2352-8729","2352-8729"],"issn-type":[{"value":"2352-8729","type":"print"},{"value":"2352-8729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70002"}}