Potential epigenetic pathways linking high mental work demands to dementia risk

Abstract

AbstractBackgroundMental demands at work are associated with dementia risk. Recent rodent studies with enriched environments suggest that epigenetic alterations moderate such an effect. Aim of the study was to investigate in whether high mental demands at work – as a form of enriched environment – are associated with epigenetic alterations on the GRIN 2B and DNMT 3B and whether this that could explain dementia risk.MethodA case‐control sample (n = 289) was randomly selected from the longitudinal population‐based AgeCoDe study of individuals age 75+. Associations between mental demands at work of the participants’ entire occupational history and methylation of GRIN 2B and DNMT 3B sites and dementia were analyzed using generalized linear regression and logistic regression models adjusted for age, gender, education, depression, diabetes, and smoking.ResultResults suggested associations between the mental work demands ‘Language & Knowledge’ and ‘Information processing’ and the methylation of six GRIN 2B sites and nine DNMT 3B sites. Results indicate that dementia risk is associated with high levels in the mental work demand ‘Language & Knowledge’ together with high methylation of the sites GRIN 2B cg05885720 (OR 0.38, p = 0.011), DNMT 3B cg13681935 (OR 0.26, p = 0.001), DNMT 3B cg13636640 (OR 0.39, p = 0.013), DNMT 3B cg22605822 (OR 0.46, p = 0.049), and a low methylation of DNMT 3B cg09835408 (OR 0.38, p = 0.017). Dementia risk was also associated with high levels in the mental work demand ‘Information Processing’ together with high methylation of the sites GRIN 2B cg05885720 (OR 0.37, p = 0.012), GRIN 2B cg14409083 (OR 0.33, p = 0.006), GRIN 2B cg03777288 (OR 0.39, p = 0.020), DNMT 3B cg22605822 (OR 0.35, p = 0.012), DNMT 3B cg13636640 (OR 0.43, p = 0.029), DNMT 3B cg08240466 (OR 0.39, p = 0.017) and low methylation of DNMT 3B cg09835408 (OR 0.36, p = 0.013).ConclusionIf what the findings suggest is true, then the protective effect of high mental demands at work against dementia is dependent on epigenetic alterations. However, our study is a first attempt to identify potential effect sizes between mental demands at work and DNA methylation on dementia risk long after retirement. Further studies with larger sample sizes need to be designed to gain a better understanding of the underlying associations.