{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T22:29:21Z","timestamp":1793572161412,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50NS108675"],"award-info":[{"award-number":["P50NS108675"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Evidence for inflammation in synucleinopathies has been building. An extensive number of studies have documented inflammatory changes in Parkinson\u2019s disease (PD), but much less is known about DLB. Post-mortem DLB brains show T-cell infiltration, and flow cytometry and cytokine\/chemokine measures in DLB subjects have suggested the presence of inflammatory responses in DLB. However, there is limited understanding if immune cell changes are present at the earliest stages of DLB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited a small, exploratory cohort of nine subjects with Mild Cognitive Impairment\u2014Lewy Bodies (MCI-LB) as part of the broader Alabama Udall cohort study, which is focused on the role of inflammation in early PD. The MCI-LB cohort was compared to subjects with <jats:italic>de novo<\/jats:italic> PD (<jats:italic>n<\/jats:italic>\u202f=\u202f64) and healthy controls (<jats:italic>n<\/jats:italic>\u202f=\u202f70) from the larger Alabama Udall cohort. Subjects underwent clinical assessments, including Movement Disorder Society-United Parkinson\u2019s Disease rating scale (MDS-UPDRS), and comprehensive cognitive assessment. Blood was obtained for flow cytometry and cytokine\/chemokine analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Demographics and medical history were comparable between groups. Significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, and MDS-UPDRS scores were observed between the groups. MCI-LB subjects had poorer cognitive composite scores compared to PD participants. MCI-LB subjects demonstrated a robust 60% reduction in mature neutrophils compared to healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data show changes in innate immune cells in MCI-LB compared to healthy controls in this small exploratory study. A larger cohort study is needed to validate these findings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1640614","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T04:13:51Z","timestamp":1756181631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammatory changes in early dementia with Lewy bodies"],"prefix":"10.3389","volume":"16","author":[{"given":"Talene 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test","author":"Hooper","year":"1983"},{"key":"ref23","volume-title":"The Boston naming test","author":"Kaplan","year":"1983"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/arclin\/11.4.329","article-title":"Benton controlled Oral word association test: reliability and updated norms","volume":"11","author":"Ruff","year":"1996","journal-title":"Arch Clin Neuropsychol"},{"key":"ref25","volume-title":"Delis-Kaplin executive function system (D-KEFS): Examiner's manual","author":"Delis","year":"2001"},{"key":"ref26","volume-title":"A compendium of neuropsychological tests: Administration, norms and commentary","author":"Spreen","year":"1998"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1093\/biomet\/75.4.800","article-title":"A sharper Bonferroni procedure for multiple tests of significance","volume":"75","author":"Hochberg","year":"1988","journal-title":"Biometrika"},{"key":"ref28","volume-title":"R: A language and environment 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