Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study

Emma L Anderson; Laura D Howe; Kaitlin H Wade; Yoav Ben-Shlomo; W David Hill; Ian J Deary; Eleanor C Sanderson; Jie Zheng; Roxanna Korologou-Linden; Evie Stergiakouli; George Davey Smith; Neil M Davies; Gibran Hemani

doi:10.1093/ije/dyz280

Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study

Int J Epidemiol. 2020 Aug 1;49(4):1163-1172. doi: 10.1093/ije/dyz280.

Authors

Emma L Anderson^{1

2}, Laura D Howe^{1

2}, Kaitlin H Wade^{1

2}, Yoav Ben-Shlomo², W David Hill³, Ian J Deary³, Eleanor C Sanderson^{1

2}, Jie Zheng^{1

2}, Roxanna Korologou-Linden^{1

2}, Evie Stergiakouli^{1

2

4}, George Davey Smith^{1

2}, Neil M Davies^{1

2}, Gibran Hemani^{1

2}

Affiliations

¹ Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
² Population Health Sciences, Bristol Medical School, University of Bristol, UK.
³ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁴ School of Oral and Dental Sciences, University of Bristol, Bristol, UK.

Abstract

Objectives: To examine whether educational attainment and intelligence have causal effects on risk of Alzheimer's disease (AD), independently of each other.

Design: Two-sample univariable and multivariable Mendelian randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on AD risk.

Participants: 17 008 AD cases and 37 154 controls from the International Genomics of Alzheimer's Project (IGAP) consortium.

Main outcome measure: Odds ratio (OR) of AD per standardized deviation increase in years of schooling (SD = 3.6 years) and intelligence (SD = 15 points on intelligence test).

Results: There was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions [OR for intelligence on education = 0.51 SD units, 95% confidence interval (CI): 0.49, 0.54; OR for education on intelligence = 0.57 SD units, 95% CI: 0.48, 0.66]. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23-49%) and 35% (95% CI: 25-43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account (OR = 1.15, 95% CI: 0.68-1.93), but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis (OR = 0.69, 95% CI: 0.44-0.88).

Conclusions: There is robust evidence for an independent, causal effect of intelligence in lowering AD risk. The causal effect of educational attainment on AD risk is likely to be mediated by intelligence.

Keywords: Alzheimer’s disease; Education; Mendelian randomization; dementia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / epidemiology
Alzheimer Disease* / genetics
Educational Status
Humans
Intelligence
Mendelian Randomization Analysis
Odds Ratio

Abstract

Publication types

MeSH terms

Grants and funding