{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:23:06Z","timestamp":1793125386799,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":61,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Systemic inflammation and innate immune activation have been implicated in dementia; however, prior studies were limited by small sample sizes. We conducted this study to evaluate the association between peripheral immune markers and the future risk of mild cognitive impairment (MCI) and dementia, their ability to differentiate between dementia causes, and their correlation with disease severity and pathological biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>On September 8, 2025, we searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible articles included cohort and case\u2013control studies assessing the association between neutrophil\u2010to\u2010lymphocyte ratio (NLR), platelet\u2010to\u2010lymphocyte ratio (PLR), or systemic inflammatory index (SII) and the risk of developing MCI or dementia, as well as their association with disease severity and pathological biomarkers. Outcomes were the risk of MCI and dementia (Alzheimer's disease, vascular dementia, and Parkinson's disease dementia), dementia severity assessed by the Mini\u2010Mental State Examination, and cerebrospinal fluid or pathological markers including amyloid beta (A\u03b2)42, A\u03b240, and tau. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled as effect estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Our analysis included 947,020 participants from 23 studies. NLR and SII, but not PLR, were associated with increased risk of dementia (NLR: HR\u00a0=\u00a01.24, 95% CI: 1.15\u22121.34; SII: HR\u00a0=\u00a01.08, 95% CI: 1.03\u22121.13) and MCI (NLR: HR\u00a0=\u00a02.78, 95% CI: 1.57\u20134.90; SII: HR\u00a0=\u00a01.28, 95% CI: 1.04\u20131.56). No differential associations were observed across dementia causes. NLR and SII were correlated with worse dementia (NLR:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.22,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.033; SII:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.17,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.041) and MCI severity (NLR:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.30,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.010; SII:\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.23,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.025). NLR, but not SII, was associated with A\u03b242, A\u03b240, and tau.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>NLR and SII may provide valuable insights when advanced biomarker testing is limited by technological or financial barriers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70270","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:55:16Z","timestamp":1780307716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Peripheral immune markers in dementia: A systematic review and meta\u2010analysis of risk, severity, and pathological correlates"],"prefix":"10.1002","volume":"12","author":[{"given":"Ahmad A.","family":"Toubasi","sequence":"first","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical 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