{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T13:05:34Z","timestamp":1775480734888,"version":"3.50.1"},"reference-count":41,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/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":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Natural Science Foundation of Sichuan Province","award":["2025ZNSFSC0589"],"award-info":[{"award-number":["2025ZNSFSC0589"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82171456"],"award-info":[{"award-number":["82171456"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Health Commission of Sichuan Province Medical Science and Technology Program","award":["24QNMP024, 24WSXT075"],"award-info":[{"award-number":["24QNMP024, 24WSXT075"]}]},{"name":"Medical Research Project of Sichuan Medical Association","award":["S2024048"],"award-info":[{"award-number":["S2024048"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While statin use is linked to cognitive impairment, causal relationships with specific dementia subtypes remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate causal effects of statin medication, genetically mimicked statin effects, and plasma lipids on various cognitive impairments using Mendelian randomization (MR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Utilizing summary genome-wide association studies data, we identified genetic variants associated with statin medication, cholesterol-dependent\/independent statin effects, and dementia subtypes, such as Alzheimer's disease (AD), dementia in Alzheimer's disease (ADD), late-onset Alzheimer's disease, dementia with Lewy body (DLB), dementia with Lewy body in\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>+<\/jats:sup>\n                      carriers, frontotemporal dementia, Parkinson's disease dementia, and vascular dementia. Univariable MR assessed causality, primarily via inverse variance weighting (IVW). Mediation effects were evaluated using the coefficient product method. Sensitivity analyses ensured robustness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IVW-MR indicated statin medication significantly reduced AD risk but increased ADD and DLB risk. Elevated total cholesterol (TC) increased dementia, ADD, and DLB, while higher low density lipoprotein cholesterol decreased AD risk. Specific\n                      <jats:italic toggle=\"yes\">DHCR24<\/jats:italic>\n                      variants reduced DLB risk, while\n                      <jats:italic toggle=\"yes\">HMGCS1<\/jats:italic>\n                      variants increased it.\n                      <jats:italic toggle=\"yes\">RAC1<\/jats:italic>\n                      variants lowered AD risk, whereas\n                      <jats:italic toggle=\"yes\">RHOC<\/jats:italic>\n                      mitigated ADD risk. Critically, TC mediated 93.91% (95% CI\u2009=\u200968.27%\u223c119.55%) of statins\u2019 effect on dementia, 84.37% (95% CI\u2009=\u200962.21%\u223c106.52%) on ADD, and 61.94% (95% CI\u2009=\u200943.47%\u223c80.42%) on DLB. The genetically mimicked effect of statins does not show a mediating role.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Statin medication, plasma lipids, and their genetic proxies exhibit causal links to cognitive impairment. Crucially, TC mediates statin-associated risks for cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25424823261440863","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T12:27:19Z","timestamp":1775478439000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the role of statin interventions on cognitive function by Mendelian randomization study"],"prefix":"10.1177","volume":"10","author":[{"given":"Yan","family":"He","sequence":"first","affiliation":[{"name":"The Second People's hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Yang","sequence":"additional","affiliation":[{"name":"The Second People's Hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Pan","sequence":"additional","affiliation":[{"name":"The Second People's Hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second People's Hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"The Second People's hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-3441","authenticated-orcid":false,"given":"Jiagui","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second People's Hospital of Yibin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/frdem.2023.1346281"},{"key":"e_1_3_3_3_2","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019","volume":"7","author":"GBD 2019 Dementia Forecasting Collaborators","year":"2022","unstructured":"GBD 2019 Dementia Forecasting Collaborators. 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