Genetic evidence that the causal association of educational attainment with reduced risk of Alzheimer's disease is driven by intelligence

Alzheimer's disease (AD) is predicted to affect 132 million people by 2050. Targeting modifiable lifestyle risk factors that are associated with an increased risk of AD could prevent a large proportion of dementia cases, allowing people to reach the end of their life dementia free. However, evidence obtained from the observational studies does not take into account how risk factors are correlated with one another, and whether they causally contribute to increased AD risk. In this study, we determine whether the relationship between previously speculated AD risk factors and AD susceptibility is consistent with causality using large-scale genetic data. We focus on educational attainment (EA), intelligence and household income which have been previously shown to be causally associated with AD. Using GWAS-by-subtraction and Multivariable Mendelian Randomization we show that of these, only the cognitive component of EA (intelligence) is independently causally associated with AD. This work has ramifications for the modifiability of lifestyle risk factors for AD. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

Alzheimer's disease (AD) is projected to affect 132 million people by 2050. This study investigates whether previously speculated AD risk factors are causally associated with AD susceptibility using large-scale genetic data. The findings suggest that only the cognitive component of educational attainment (intelligence) is independently causally linked to AD.