{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:45Z","timestamp":1789538685972,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuroinflammation is a key driver of Alzheimer\u2019s disease (AD). Although the neutrophil-to-lymphocyte ratio (NLR) is an easily accessible peripheral inflammatory marker, yet its longitudinal association with domain-specific cognitive decline and the underlying neuropathological mechanisms during the preclinical and early stages of AD remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 1,190 non-people living with dementia older adults from the AD Neuroimaging Initiative cohort were included, comprising 405 cognitively normal participants and 785 participants with mild cognitive impairment (MCI). Participants were stratified according to baseline NLR (\u2265 3versus\u202f&amp;lt;\u202f3). Linear mixed-effects models were used to examined the association between baseline NLR and longitudinal decline across multiple cognitive domains. Cox proportional hazards model assessed progression risk to MCI or AD. Mediation analyses evaluated whether cerebrospinal fluid (CSF) biomarkers, including amyloid-\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      (A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      ), total tau (t-tau), and phosphorylated tau (p-tau), statistically accounted for the association between NLR and cognitive decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During follow-up, a high baseline NLR (\u2265 3) was independently associated with accelerated decline in global cognition, memory, executive function, language, and visuospatial abilities (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05), as well as a 20% higher risk of clinical progression per 1-unit increase in NLR (hazard ratio\u202f=\u202f1.20, 95% confidence interval: 1.12\u20131.29,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001). Mediation analyses indicated that CSF t-tau and p-tau, but not A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      , partially explained the association between NLR and cognitive decline. The observed associations remained robust across sensitivity and subgroup analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Elevated NLR was significantly and independently associated with accelerated decline across multiple cognitive domains and an increased risk of clinical progression in older adults at risk for AD. The observed associations with tau pathology are consistent with a potential role for peripheral immune dysregulation in early disease trajectories; however, formal predictive modeling and external validation are required before clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1872617","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:42Z","timestamp":1789536702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil-to-lymphocyte ratio predicts early cognitive decline associated with tau pathology in Alzheimer\u2019s disease: a longitudinal study of the ADNI cohort"],"prefix":"10.3389","volume":"18","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Neurological Diseases of Guangxi Province, Guilin Medical University","place":["Guilin, China"]},{"name":"Key Laboratory of Environmental Exposomics and Entire Lifecycle Health of Guangxi Province, Guilin Medical University","place":["Guilin, China"]},{"name":"Key Laboratory of Brain and Cognition of Guangxi Province, Guilin Medical University","place":["Guilin, China"]},{"name":"Key Laboratory of Diabetic Systems Medicine of Guangxi Province, Guilin Medical University","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenle","family":"Jia","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Department, Shanxi Province Cancer Hospital\/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences\/Cancer Hospital Affiliated to Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1002\/jcsm.12442","article-title":"Association of Lifestyle Factors and Inflammation with Sarcopenic obesity: data from the Predimed-Plus trial","volume":"10","author":"Abete","year":"2019","journal-title":"J. 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