Working status and risk of Alzheimer's disease: A Mendelian randomization study

Abstract

Background: Alzheimer's disease (AD) has become a common illness affecting the elderly, adding to society's social and financial burden. We used two-sample Mendelian randomization (MR) in this study to determine the association between working status and AD. Methods:We performed a two-sample MR analysis. The genetic associations were derived from the UK Biobank (n = 263,615) and the International Genomics of Alzheimer's Project (n = 63,926). Inverse variance weighted (IVW), MR-Egger, and weighted median were used in the MR analysis. The funnel plot, Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used in sensitivity analyses.Further risk factor analyses were carried out to look into the potential mediators.Results: Jobs involve heavy manual or physical work (OR = 2.13, 95%CI 1.36-3.36; p = .0011), job involves mainly walking or standing (OR = 1.74, 95%CI 1.19-2.54; p = .004), and job involves shift work (OR = 2.78, 95%CI 1.14-6.80; p = .02) increased the risk of AD in the IVW analysis. There was no heterogeneity and no horizontal pleiotropy in the sensitivity analysis. Risk factor analysis suggested that each of the above association may be mediated by different risk factors. Conclusion:Our study adds to the evidence that the development of AD is associated with the working status (job involves heavy manual or physical work, job involves mainly walking or standing, and job involves shift work) by using extensive human genetic data.

Work‐related factors and risk of amyotrophic lateral sclerosis: A multivariable Mendelian randomization study

“…Work‐related factors have been recognized to influence the development of neurodegenerative diseases including dementia, Alzheimer's disease, and ALS. It has been shown that manual work is positively associated with the risk of developing Alzheimer's disease (Zhao et al., 2023 ). The risk of all‐cause dementia is increased in the shift‐working population (Liao et al., 2022 ).…”

“…MR methods are also known as natural RCTs because the process of assigning alleles from parent to offspring is similar to random grouping in RCT (Davies et al., 2018 ), and thus, MR methods can overcome some of the limitations in observational studies and minimize confounding factors and reverse causality (Davey Smith & Hemani, 2014 ). The effect of work‐related factors on some neurodegenerative diseases such as Alzheimer's disease has been demonstrated by MR (Zhao et al., 2023 ), but there is still a lack of MR studies of work‐related factors on ALS.…”

Small Molecular Fluorescent Probes for Alzheimer's Disease Associated Active Species

“…Despite the significant investments in neurological research, the exact molecular mechanism of AD pathogenesis is still not fully elucidated [4,5] . AD, therefore, would develop into a crucial threat to the public health and cause huge financial burden to the social welfare system, if we cannot innovate AD diagnostic and therapeutic paradigms in time [6,7] …”

“…[4,5] AD, therefore, would develop into a crucial threat to the public health and cause huge financial burden to the social welfare system, if we cannot innovate AD diagnostic and therapeutic paradigms in time. [6,7] Generally, the clinical manifestations of AD mainly include memory loss, language impairment, progressive mental decline, personality and behavior changes. [8] Currently, clinical examination and neuropsychological tests are still the general standard for definite diagnosis of AD.…”