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Causation was further assessed using Mendelian randomization (MR).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR]\u00a0=\u00a02.37, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and major depressive disorder (MDD; HR\u00a0=\u00a01.63, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). MR confirmed a causal link between BD and AD (OR<jats:sub>IVW\u00a0<\/jats:sub>=\u00a01.098), as well as obsessive\u2010compulsive disorder (OCD) and AD (OR<jats:sub>IVW\u00a0<\/jats:sub>=\u00a01.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR]\u00a0=\u00a02.37, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), followed by those with major depressive disorder (MDD; HR\u00a0=\u00a01.63, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR\u00a0=\u00a02.36, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.056).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two\u2010sample Mendelian randomization (MR) confirmed a causal association between BD and AD (OR<jats:sub>IVW\u00a0<\/jats:sub>=\u00a01.098, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), as well as AD family history (proxy\u2010AD, OR<jats:sub>IVW\u00a0<\/jats:sub>=\u00a01.098, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive\u2010compulsive disorder (OCD) spectrum and AD (OR<jats:sub>IVW\u00a0<\/jats:sub>=\u00a01.050, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14049","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T14:47:15Z","timestamp":1718117235000},"page":"4841-4853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis"],"prefix":"10.1002","volume":"20","author":[{"given":"Yiliang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Central South University  Changsha China"},{"name":"Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South University  Changsha China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Xiangya Hospital Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Central South University  Changsha China"},{"name":"Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South University  Changsha China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Xiangya Hospital Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Central South University  Changsha China"},{"name":"Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South University  Changsha China"},{"name":"Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Xiangya Hospital Changsha China"},{"name":"Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)32205\u20104"},{"key":"e_1_2_8_3_1","unstructured":"ICD\u201011. 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