{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:26:30Z","timestamp":1793413590872,"version":"4.5.0"},"reference-count":35,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"unspecified","delay-in-days":114,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epidemiol Psychiatr Sci"],"published-print":{"date-parts":[[2020]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S2045796020000347_sec_a1\" sec-type=\"other\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In observational studies, type-2 diabetes is associated with increased risk of dementia; however, the causal nature of this association remains unanswered. In an unselected nationwide study of all Danes, we wanted to test whether type-2 diabetes is associated with dementia subtypes, and to test whether potential associations are of a causal nature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S2045796020000347_sec_a2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the current study of nationwide observational registry data in all Danes above the age of 65 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 784 434) combined with genetic consortia data on 213 370 individuals, we investigated the associations between type-2 diabetes and Alzheimer's disease, vascular dementia, unspecified dementia and all-cause dementia, and whether observational associations were of a causal nature by applying a two-sample Mendelian randomisation strategy. We addressed key biases inherent in Mendelian randomisation approaches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S2045796020000347_sec_a3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Important confounders (age, ethnicity, size of community, region, civil status and education level) were captured on all 784 434 individuals and adjusted for in the models. Multifactorial adjusted hazard ratios were 1.13 (1.06\u20131.21) for Alzheimer's disease, 1.98 (1.83\u20132.14) for vascular dementia, 1.53 (1.48\u20131.59) for unspecified dementia and 1.48 (1.44\u20131.53) for all-cause dementia in persons with type-2 diabetes\n                      <jats:italic>v<\/jats:italic>\n                      . without. Results were similar for men and women. The two-sample Mendelian randomisation estimate for the association between the genetic instrument and Alzheimer's disease was 1.04 (0.98\u20131.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias and weak instrument bias.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S2045796020000347_sec_a4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a nationwide study of all Danes above the age of 65 years, we show that type-2 diabetes is associated with major subtypes of dementia \u2013 with particularly strong associations for vascular dementia and unspecified dementia \u2013 the two types of dementia with the most obvious vascular pathologies. Although the present two-sample Mendelian randomisation approach using genetic consortia data suggests that type-2 diabetes is not a direct cause of Alzheimer's disease, we were unable to test the causal nature of type-2 diabetes for vascular dementia and unspecified dementia, because no publicly available genetic consortia data yet exist for these dementia endpoints. The causal nature of type-2 diabetes for dementia with vascular pathologies is pivotal questions to solve for future public health recommendations and therapeutic advice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s2045796020000347","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T03:59:28Z","timestamp":1587700768000},"source":"Crossref","is-referenced-by-count":67,"title":["Type-2 diabetes and risk of dementia: observational and Mendelian randomisation studies in 1 million individuals"],"prefix":"10.1017","volume":"29","author":[{"given":"Jesper Qvist","family":"Thomassen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne Schurmann","family":"Tolstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Benn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4084-5027","authenticated-orcid":false,"given":"Ruth","family":"Frikke-Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"S2045796020000347_ref35","volume-title":"Global report on diabetes","year":"2016"},{"key":"S2045796020000347_ref34","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161194"},{"key":"S2045796020000347_ref31","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"S2045796020000347_ref30","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1253"},{"key":"S2045796020000347_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67601-5"},{"key":"S2045796020000347_ref28","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12476"},{"key":"S2045796020000347_ref33","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy195"},{"key":"S2045796020000347_ref27","article-title":"World Alzheimer report 2014, Dementia and risk reduction","author":"Price","year":"2014","journal-title":"Alzheimer's Disease International"},{"key":"S2045796020000347_ref29","unstructured":"Rasmussen, KL (2016). Plasma levels of apolipoprotein E and risk of dementia and ischemic heart disease in the general population (PhD thesis). Faculty of Health and Medical Sciences, University of Copenhagen."},{"key":"S2045796020000347_ref25","first-page":"441","article-title":"The Danish Civil Registration System: a cohort of eight million persons","volume":"53","author":"Pedersen","year":"2006","journal-title":"Danish Medical Bulletin"},{"key":"S2045796020000347_ref24","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr178"},{"key":"S2045796020000347_ref23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001841"},{"key":"S2045796020000347_ref7","first-page":"1961","article-title":"Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic","volume":"45","author":"Bowden","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"S2045796020000347_ref6","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"S2045796020000347_ref13","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12087"},{"key":"S2045796020000347_ref18","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"S2045796020000347_ref26","first-page":"220","article-title":"Validity of dementia diagnoses in the Danish hospital registers","volume":"7","author":"Phung","year":"2011","journal-title":"Dementia and Geriatric Cognitive Disorders"},{"key":"S2045796020000347_ref9","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"S2045796020000347_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.12.006"},{"key":"S2045796020000347_ref5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j1648"},{"key":"S2045796020000347_ref3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000247053.45483.4e"},{"key":"S2045796020000347_ref8","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"S2045796020000347_ref19","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5375"},{"key":"S2045796020000347_ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-0011-z"},{"key":"S2045796020000347_ref15","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000222409.00878.37"},{"key":"S2045796020000347_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31363-6"},{"key":"S2045796020000347_ref16","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180644"},{"key":"S2045796020000347_ref2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu779"},{"key":"S2045796020000347_ref4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01922"},{"key":"S2045796020000347_ref11","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2337\/dc15-1588","article-title":"Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia","volume":"39","author":"Chatterjee","year":"2016","journal-title":"Diabetes Care"},{"key":"S2045796020000347_ref12","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-base platform supports systematic causal inference across the human phenome","volume":"7","author":"Gibran","year":"2018","journal-title":"eLife"},{"key":"S2045796020000347_ref14","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102"},{"key":"S2045796020000347_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)92972-7"},{"key":"S2045796020000347_ref21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001982"},{"key":"S2045796020000347_ref22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32152-9"}],"container-title":["Epidemiology and Psychiatric Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S2045796020000347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T01:45:36Z","timestamp":1666403136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S2045796020000347\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":35,"alternative-id":["S2045796020000347"],"URL":"https:\/\/doi.org\/10.1017\/s2045796020000347","relation":{},"ISSN":["2045-7960","2045-7979"],"issn-type":[{"value":"2045-7960","type":"print"},{"value":"2045-7979","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]},"article-number":"e118"}}