{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:54:31Z","timestamp":1791266071920,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program of Hangzhou Science and Technology Bureau","award":["20241203A17"],"award-info":[{"award-number":["20241203A17"]}]},{"name":"Zhejiang Province Leading Geese Plan","award":["2024C03099"],"award-info":[{"award-number":["2024C03099"]}]},{"name":"Major Projects of Hangzhou Health Science and Technology","award":["Z20220024"],"award-info":[{"award-number":["Z20220024"]}]}],"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>Previous studies on the association between statin use and the risk of Alzheimer\u2019s disease (AD) have yielded inconsistent results. This study, based on the large-scale UK Biobank cohort, evaluates the relationship between statin use and the risk of new-onset AD, survival in patients with AD, and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 502,401 participants with a median follow-up of 9.24\u202fyears. The association between statin use and the risk of AD was analyzed using Cox proportional hazards models, logistic regression, and propensity score matching. The robustness of the results was assessed through internal validation using training and validation groups, as well as subgroup analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 975 new cases of AD were recorded. Multivariate Cox regression analysis showed that statin use was associated with a reduced risk of AD (HR\u202f=\u202f0.72, 95% CI: 0.52\u20130.98;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05), and the results remained consistent after propensity score matching (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Among individuals aged \u226565\u202fyears, statin users demonstrated better cognitive performance than non-users. Concomitant use of antihypertensive or antidiabetic medications did not significantly alter the protective effect of statins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Statin use was associated with a modestly lower risk of AD and slower cognitive decline. These findings highlight the importance of enhanced clinical awareness in identifying AD patients and those at risk of adverse outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1961033","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:47Z","timestamp":1791264107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of statin use with reduced risk of Alzheimer\u2019s disease: findings in UK Biobank"],"prefix":"10.3389","volume":"18","author":[{"given":"Hui","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"School of Pharmacy, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"School of Pharmacy, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"He","sequence":"additional","affiliation":[{"name":"School of Public Health Management, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"School of Pharmacy, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Laboratory of Medicine, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Zhejiang Key Laboratory of Zero Magnetic Medicine, Affiliated Hangzhou First People\u2019s Hospital, School of Medicine, Westlake University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1002\/alz.12707","article-title":"Hypertension and Alzheimer's disease pathology at autopsy: a systematic review","volume":"18","author":"Abdulrahman","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41569-018-0098-5","article-title":"Safety and efficacy of statin therapy","volume":"15","author":"Adhyaru","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1001\/jama.286.1.64","article-title":"Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation\/CRP evaluation (PRINCE): a randomized trial and cohort study","volume":"286","author":"Albert","year":"2001","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"6187","DOI":"10.1038\/s41598-020-63035-2","article-title":"The cognitive effects of statins are modified by age","volume":"10","author":"Alsehli","year":"2020","journal-title":"Sci. Rep."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1097\/01.JGP.0000310778.20870.ae","article-title":"Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis","volume":"16","author":"Anstey","year":"2008","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1212\/01.wnl.0000288181.00826.63","article-title":"Statins, incident Alzheimer disease, change in cognitive function, and neuropathology","volume":"70","author":"Arvanitakis","year":"2008","journal-title":"Neurology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1001\/jama.2021.4001","article-title":"Association between age at diabetes onset and subsequent risk of dementia","volume":"325","author":"Barbiellini Amidei","year":"2021","journal-title":"JAMA"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrendo.2015.194","article-title":"The diabetogenic action of statins - mechanisms and clinical implications","volume":"12","author":"Betteridge","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3389\/fphys.2020.00598","article-title":"Involvement of lipids in Alzheimer's disease pathology and potential therapies","volume":"11","author":"Chew","year":"2020","journal-title":"Front. Physiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e70280","DOI":"10.1002\/prp2.70280","article-title":"The use of statins in Parkinson's and Alzheimer's disease: a 2021-2025 state-of-the-art review of clinical and preclinical evidence","volume":"14","author":"Chiatto","year":"2026","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"349","DOI":"10.17219\/acem\/131216","article-title":"Cerebral small vessel disease: a review","volume":"30","author":"Chojdak-\u0141ukasiewicz","year":"2021","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43044-023-00327-8","article-title":"Pleotropic effects of statins: the dilemma of wider utilization of statin","volume":"75","author":"Choudhary","year":"2023","journal-title":"Egypt. Heart J."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1007\/s11011-017-0015-3","article-title":"Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions","volume":"32","author":"Czuba","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e12156","DOI":"10.1002\/trc2.12156","article-title":"Sex and APOE genotype differences related to statin use in the aging population","volume":"7","author":"Dagliati","year":"2021","journal-title":"Alzheimers Dement. (N Y)"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S1474-4422(19)30393-X","article-title":"Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies","volume":"19","author":"Ding","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0231627","DOI":"10.1371\/journal.pone.0231627","article-title":"Reliability and validity of the UK biobank cognitive tests","volume":"15","author":"Fawns-Ritchie","year":"2020","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"100389","DOI":"10.1016\/j.cccb.2025.100389","article-title":"Statin treatment for cerebral small vessel disease: a systematic review and meta-analysis of randomized controlled trials","volume":"9","author":"Fresnais","year":"2025","journal-title":"Cereb. Circ. Cogn. Behav."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1159\/000535422","article-title":"Cerebrovascular hemodynamics in cognitive impairment and dementia: a systematic review and Meta-analysis of transcranial Doppler studies","volume":"52","author":"Fresnais","year":"2023","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13195-017-0237-y","article-title":"Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease","volume":"9","author":"Geifman","year":"2017","journal-title":"Alzheimer's Res. Ther."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1007\/s00204-023-03492-6","article-title":"Understanding the molecular mechanisms of statin pleiotropic effects","volume":"97","author":"German","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref21","first-page":"1","article-title":"Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003-2012","volume":"177","author":"Gu","year":"2014","journal-title":"NCHS Data Brief"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/S1474-4422(08)70169-8","article-title":"Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors","volume":"7","author":"Kalaria","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.1600-0404.2006.00685.x","article-title":"Cholesterol as a risk factor for Alzheimer's disease - epidemiological evidence","volume":"185","author":"Kivipelto","year":"2006","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer's disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1111\/joim.13134","article-title":"Statin exposure and the risk of dementia in individuals with hypercholesterolaemia","volume":"288","author":"Lee","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the lancet standing commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.jsbmb.2019.03.003","article-title":"Alterations in cholesterol metabolism as a risk factor for developing Alzheimer's disease: potential novel targets for treatment","volume":"190","author":"Loera-Valencia","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e0154222","DOI":"10.1371\/journal.pone.0154222","article-title":"Cognitive test scores in UK biobank: data reduction in 480,416 participants and longitudinal stability in 20,346 participants","volume":"11","author":"Lyall","year":"2016","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.atherosclerosis.2019.11.020","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"290","author":"Mach","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s11883-025-01386-9","article-title":"Pleiotropic effects of statins: focus on inflammation, oxidative stress and immunomodulation (part I)","volume":"28","author":"Mahmoudi","year":"2026","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"Cd003160","DOI":"10.1002\/14651858.cd003160.pub3","article-title":"Statins for the prevention of dementia","volume":"2016","author":"McGuinness","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/ana.26670","article-title":"A comparison between early presentation of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease: evidence from routine primary care and UK biobank data","volume":"94","author":"Nedelec","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1093\/eurjpc\/zwab208","article-title":"Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies","volume":"29","author":"Olmastroni","year":"2022","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/s11606-014-3115-3","article-title":"Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials","volume":"30","author":"Ott","year":"2015","journal-title":"J. Gen. Intern. Med."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1001\/archneur.60.1.29","article-title":"Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism","volume":"60","author":"Papassotiropoulos","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13195-023-01360-0","article-title":"Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study","volume":"15","author":"Petek","year":"2023","journal-title":"Alzheimer's Res. Ther."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nrneurol.2015.35","article-title":"Statins, cognition, and dementia\u2014systematic review and methodological commentary","volume":"11","author":"Power","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1159\/000115847","article-title":"Plasma lipid levels in the elderly are not associated with the risk of mild cognitive impairment","volume":"25","author":"Reitz","year":"2008","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"101006","DOI":"10.1016\/j.lanwpc.2023.101006","article-title":"Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong","volume":"44","author":"Ren","year":"2024","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1002\/alz.13543","article-title":"Statin use moderates APOE'S and CRP'S associations with dementia and is associated with lesser dementia severity in \u03b54 carriers","volume":"20","author":"Royall","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"6460","DOI":"10.1073\/pnas.95.11.6460","article-title":"Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons","volume":"95","author":"Simons","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1600-0404.2006.00690.x","article-title":"Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's disease cholesterol-lowering treatment (ADCLT) trial","volume":"185","author":"Sparks","year":"2006","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.3390\/genes16121494","article-title":"APOE genotype and endothelial biomarkers: towards personalized cardiovascular screening","volume":"16","author":"Titolo","year":"2025","journal-title":"Genes (Basel)"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6518","DOI":"10.3390\/ijms24076518","article-title":"Inflammatory processes in Alzheimer's disease-pathomechanism, diagnosis and treatment: a review","volume":"24","author":"Twarowski","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"695","DOI":"10.4103\/1673-5374.391305","article-title":"Liver as a new target organ in Alzheimer's disease: insight from cholesterol metabolism and its role in amyloid-beta clearance","volume":"20","author":"Wu","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.cca.2016.02.024","article-title":"Imbalanced cholesterol metabolism in Alzheimer's disease","volume":"456","author":"Xue-Shan","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"101131","DOI":"10.1016\/j.yfrne.2024.101131","article-title":"Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis","volume":"73","author":"Youn","year":"2024","journal-title":"Front. Neuroendocrinol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"n604","DOI":"10.1136\/bmj.n604","article-title":"Associations of healthy lifestyle and socioeconomic status with mortality and incident cardiovascular disease: two prospective cohort studies","volume":"373","author":"Zhang","year":"2021","journal-title":"BMJ"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1016\/j.jacc.2021.04.075","article-title":"Effect of statin therapy on cognitive decline and incident dementia in older adults","volume":"77","author":"Zhou","year":"2021","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1961033\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:48Z","timestamp":1791264108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1961033\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":50,"alternative-id":["10.3389\/fnagi.2026.1961033"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1961033","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1961033"}}