{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T17:34:27Z","timestamp":1768412067759,"version":"3.49.0"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010241"],"award-info":[{"award-number":["2023A1515010241"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychogeriatrics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Observational investigations have reported correlations between brain imaging\u2010derived phenotypes (IDPs) and dementia, as well as dysfunctions in brain resting\u2010state functional networks in dementia patients. However, the causal nature of these relationships remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Herein we applied bidirectional two\u2010sample Mendelian randomisation analysis to infer the causal relationships between 587 IDPs (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200933\u2009224) and 191 brain resting\u2010state functional networks (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934\u2009691) with dementia and its sub\u2010types (AD, PDD, FTD and DLB;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093024\u2013216\u2009771) using genetic variants\u2010single nucleotide polymorphism (SNPs) as instrumental variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The forward MR identified 14 IDP phenotypes that are causally related to the risk of dementia, including frontotemporal dementia (FTD) and Lewy body dementia (DLB). For example, a decrease in the thickness of the right rostral middle frontal cortex was strongly associated with an increased risk of dementia. The reverse MR analysis revealed significant associations between 153 IDP phenotypes and the risk of FTD and DLB and between 73 rs\u2010fMRI phenotypes and the risk of dementia and AD. For instance, a higher risk of DLB was associated with a decrease in FA in the right posterior thalamic radiation. Additionally, the risk of Alzheimer's disease dementia is causally associated with reduced connectivity in the default mode and salience networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We identified 14\n                      <jats:styled-content style=\"fixed-case\">IDPs<\/jats:styled-content>\n                      causally associated with dementia or its subtypes. We also identified potential causal effects of\n                      <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>\n                      on 153\n                      <jats:styled-content style=\"fixed-case\">IDPs<\/jats:styled-content>\n                      and dementia and\n                      <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                      on 73 rs\u2010\n                      <jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>\n                      phenotypes. Our findings provide insights into the aetiology of dementia and highlight structural brain changes and functional network impairments throughout the disease process. Furthermore, these results contribute to the identification of potential imaging\u2010based predictors and therapeutic targets for dementia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/psyg.70126","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:57:35Z","timestamp":1767679055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Causal Relationships Between Brain Imaging Phenotypes and Dementia and Its Subtypes: Comprehensive Analysis of Structural and Resting\u2010State Functional Imaging"],"prefix":"10.1111","volume":"26","author":[{"given":"Shu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhensheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital, Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingdun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology First People's Hospital of Foshan  Foshan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8663-5837","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12901"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160484"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocn.16444"},{"key":"e_1_2_12_6_1","article-title":"Epidemiology and Pathophysiology of Dementia\u2010Related Psychosis","volume":"81","author":"Aarsland D.","year":"2020","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-023-01441-w"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.5694\/mja2.51996"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02215-8"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-02939-3"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010231"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2021-326571"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-019-0695-y"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-024-01879-8"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2024.09.049"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2019"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq2591"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0579-23.2023"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00125-4"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2022.102471"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2002.1114"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102159"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49300-2"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq075"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01612-2"},{"key":"e_1_2_12_26_1","first-page":"384","article-title":"Dementia Prevention: The Mendelian Randomisation Perspective","volume":"95","author":"Anderson E. L.","year":"2024","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00826-4"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0571-7"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22856"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22068"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.02.024"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10609"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01039-6"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009238"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30367-6"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0164-2"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6522"},{"key":"e_1_2_12_41_1","first-page":"1961","article-title":"Assessing the Suitability of Summary Data for Two\u2010Sample Mendelian Randomization Analyses Using Mr\u2010Egger Regression: The Role of the I\n                  2 Statistic","volume":"45","author":"Bowden J.","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22488"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr198"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24296"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000250326.77323.01"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2023.10.009"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2015.00474"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2014.03.013"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.03.007"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22414"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000100"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112867"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00208"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00462-6"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl388"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e0f7cf"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.10.026"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac094"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318266fc51"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00758-3"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01422-x"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12760"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-015-4178-1"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00684-4"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.11.028"}],"container-title":["Psychogeriatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/psyg.70126","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/psyg.70126","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/psyg.70126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:21:33Z","timestamp":1768386093000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/psyg.70126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/psyg.70126"],"URL":"https:\/\/doi.org\/10.1111\/psyg.70126","archive":["Portico"],"relation":{},"ISSN":["1346-3500","1479-8301"],"issn-type":[{"value":"1346-3500","type":"print"},{"value":"1479-8301","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70126"}}