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Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neurodegenerative diseases (NDDs) including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective cohort analysis using a large propensity-score-matched population (\n                      <jats:italic>n<\/jats:italic>\n                      = 190,308; 95,154 treated vs. 95,154 untreated) to evaluate associations between long-term AIT exposure and incidence of major NDDs. Disease-specific and combined outcomes were assessed across drug classes (NSAIDs, corticosteroids, immunomodulators), sex, age, and therapy duration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AIT exposure was associated with a significantly lower risk of developing any NDD (RR = 0.47, 95% CI 0.43\u20130.48,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.0001) and was equally effective in both sexes. Risk reduction was observed for each age-associated disease: AD (RR = 0.40), non-AD dementia (RR = 0.51), PD (RR = 0.43), MS (RR = 0.25), and ALS (RR = 0.48). Among drug classes, immunomodulators conferred the greatest reduction (RR = 0.19), followed by corticosteroids (RR = 0.41) and NSAIDs (RR = 0.42). Duration analyses revealed a graded benefit, with RR declining from 0.94 ( &amp;lt; 1 year) to 0.25 ( &amp;gt; 6 years). Risk reduction was greatest in older participants (75\u201379 years).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Chronic use of anti-inflammatory or immunomodulatory therapies was associated with significantly reduced incidence of multiple neurodegenerative diseases in both sexes. The strongest effects were observed with immunomodulator use and prolonged therapy duration, suggesting that sustained modulation of systemic inflammation confers broad neuroprotective effects in both sexes. These findings highlight the potential of targeting immune-inflammatory pathways for neurodegenerative disease prevention and can inform prospective mechanistic and interventional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1818660","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:43:39Z","timestamp":1779083019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-inflammatory and immunomodulatory therapies are associated with reduced risk of age-associated neurodegenerative diseases: impact of sex and treatment duration"],"prefix":"10.3389","volume":"18","author":[{"given":"Helena","family":"Cortes-Flores","sequence":"first","affiliation":[{"name":"Center for Innovation in Brain Science, University of Arizona","place":["Tucson, AZ, United States"]},{"name":"Department of Pharmacology, University of Arizona College of Medicine","place":["Tucson, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Torrandell-Haro","sequence":"additional","affiliation":[{"name":"Center for Innovation in Brain Science, University of Arizona","place":["Tucson, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta Diaz","family":"Brinton","sequence":"additional","affiliation":[{"name":"Center for Innovation in Brain Science, University of Arizona","place":["Tucson, AZ, United States"]},{"name":"Department of Pharmacology, University of Arizona College of Medicine","place":["Tucson, AZ, United States"]},{"name":"Department of Neurology, University of Arizona College of Medicine","place":["Tucson, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jalz.2008.09.004","article-title":"Alzheimer\u2019s disease anti-inflammatory prevention trial: Design, methods, and baseline results.","volume":"5","author":"Meinert","year":"2009","journal-title":"Alzheimers Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e4620","DOI":"10.7759\/cureus.4620","article-title":"Recommendations for anti-inflammatory treatments in alzheimer\u2019s disease: A comprehensive review of the literature.","volume":"11","author":"Ali","year":"2019","journal-title":"Cureus"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/alz.13809","article-title":"2024 Alzheimer\u2019s disease facts and figures.","volume":"20","year":"2024","journal-title":"Alzheimers Dement."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e70514","DOI":"10.1002\/alz.70514","article-title":"Cytokines and immune biomarkers in neurodegeneration and cognitive function: A systematic review among individuals of African ancestry.","volume":"21","author":"Antwi","year":"2025","journal-title":"Alzheimers Dement."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.3390\/ph15091077","article-title":"Current advancement of immunomodulatory drugs as potential pharmacotherapies for autoimmunity based neurological diseases.","volume":"15","author":"Ashraf","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nri.2016.123","article-title":"Cytokine networks in neuroinflammation.","volume":"17","author":"Becher","year":"2017","journal-title":"Nat. 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