# Effect sizes of APOE e4 on the same general cognitive ability test taken by the same people from age 11 to age 90: The Lothian Birth Cohorts 1921 and 1936

## TL;DR

This study shows that the APOE e4 gene variant has little effect on cognitive ability in youth but becomes more harmful with age, especially in older adults.

## Contribution

The study reveals a linear increase in the negative effect of APOE e4 on cognition from age 11 to 90.

## Key findings

- APOE e4 effect size was near zero at age 11 and 70 but reached beta = 0.30 at age 90.
- Adjusting for medical conditions had minimal impact on APOE e4 effect sizes.
- Removing participants with dementia reduced effect sizes by a third to a half.

## Abstract

Variation in the gene for apolipoprotein E (APOE) is one of the few variables that is associated with individual differences in age-related cognitive decline in humans. Therefore, it is important to understand the conditions that affect the strength of its effect. Here we examine how the effect size of APOE variation (possession of one or more e4 alleles) on a test of general cognitive ability changes with age from 11 to 90 years. The data are from the Lothian Birth Cohorts of 1936 and 1921 who took the same cognitive test (the Moray House Test) at, respectively, 11, 70, 73, 79, and 11, 79, 87, 90. The standardised absolute effect of APOE e4 on general cognitive ability was about zero at ages 11 (beta < 0.05) and 70 (beta ≤ 0.025) and increased linearly to beta = 0.30 (p < 0.001) at age 90. The effect sizes were minimally affected by adjusting for medical conditions (hypertension, diabetes, cardiovascular disease, stroke). However, the results were less robust to removing those participants who had developed dementia; effect sizes were reduced by about a third to a half, and were largely non-significant. The results suggest that the negative effect of APOE e4 on cognitive functioning becomes greater with age; this urges more work to understand the mechanisms by which e4 status renders the older person’s brain increasingly vulnerable to cognitive decline and dementia.