Examining the non-linear effects of education on Alzheimer's and non-Alzheimer's disease: Sex-stratified analysis of 17,671 older persons

Abstract

Background: Higher educational attainment is strongly associated with a reduced risk of neurocognitive disorders (NCDs). However, the literature is not yet clear on (1) the minimum years of compulsory education that would sufficiently mitigate the risk of NCDs, and (2) whether educational attainment has differential effects across sexes. To bridge these gaps, this study sought to model potential non-linear relationship between years of education and NCD risk, across men and women.

Methods: The study recruited 17,671 participants from Alzheimer's Disease Centres across United States, aged≥50 years and had normal cognition at baseline. Participants were followed up almost annually, and underwent standardized assessments to diagnose various aetiologies of NCDs. Cox proportional hazard regression was conducted to examine the relationship between years of education and NCD risk, stratified by sexes. Years of education were modelled using restricted cubic spline.

Results: Lesser years of education were associated with higher NCD risk in both sexes (specifically, when <12 years of education; HR 1.80-3.48), yet with key differences across sexes. In women, a linear relationship was observed whereby increasing years of education reduced NCD risk correspondingly; but in men, the relationship was non-linear whereby adding years of education beyond 12 years did not reduce NCD risk further. Men of lower educational attainment were at risk of both Alzheimer's Disease (AD; HR up to 3.45) and non-AD (HR up to 2.57), while women of lower educational attainment were only at risk of AD (HR up to 2.11).

Conclusions: Educational attainment alters NCD risk differently across sexes, emphasizing the relevance of sex-specific research to better understand the moderating role of sex on NCD risk. The findings also highlight the need to reconsider public policies related to equitable access to education, as well as traditional assumptions on the minimum years of compulsory education.

Keywords: Alzheimer's disease; Education attainment; Minimum education; Neurocognitive disorder.