Affiliation:
1. Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical
2. Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, 8 Australia
3. School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian China
4. Neurodegenerative Laboratory of Ministry of Education of the People’s Republic of China, Beijing, China
Abstract
Background: Extensive studies put forward the association between Alzheimer’s disease (AD) and psychiatric disorders; however, it remains unclear whether these associations are causal. Objective: We aimed to assess the potential causal relationship between major psychiatric disorders and AD. Methods: A bidirectional two-sample Mendelian randomization (MR) was applied to evaluate potential causality between five psychiatric disorders and AD by selecting the single-nucleotide polymorphisms from the genome-wide association studies as instrumental variables. Inverse-variance weighted (IVW) method was used as the main analyzing approach to estimate possible causal effects, alternative methods including MR-Egger, the MR pleiotropy residual sum and outlier, and leave-one-out analysis method were implemented as sensitivity analyzing approaches to ensure the robustness of results. Results: All forward and reverse MR analyses consistently suggested absent causal relations between psychiatric disorders and AD risk [forward IVW: ORADHD, 1.030, 95% CI, 0.908–1.168, p = 0.674; ORanxiety disorders, 0.904, 95% CI, 0.722–1.131, p = 0.377; ORASD, 0.973, 95% CI, 0.746–1.272, p = 0.846; ORBIP, 1.033, 95% CI, 0.925–1.153, p = 0.564; and ORschizophrenia, 1.039, 95% CI, 0.986–1.095, p = 0.156; reverse IVW: ORADHD, 0.993, 95% CI, 0.954–1.034, p = 0.746; ORanxiety disorders, 1.000, 95% CI, 0.999–1.000, p = 0.898; ORASD, 1.001, 95% CI, 0.962–1.042, p = 0.949; ORBIP, 0.997, 95% CI, 0.966–1.028, p = 0.831; and ORschizophrenia, 1.013, 95% CI, 0.978–1.051, p = 0.466]. Conclusion: There is no significant evidence supporting the causal association between the five major psychiatric disorders and AD.
Subject
Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience
Reference62 articles.
1. Alzheimer’s disease;Scheltens;Lancet,2016
2. Prince MJ , Wimo A , Guerchet MM , Ali GC , Wu Y-T , Prina M (2015) World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International, London.
3. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: The Cache County Study;Steinberg;Int J Geriatr Psychiatry,2008
4. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: The Cache County Dementia Progression Study;Peters;Am J Psychiatry,2015
5. Risk of dementia in adults with ADHD: A nationwide, population-based cohort study in Taiwan;Tzeng;J Atten Disord,2019