APOE e4 is the largest genetic risk factor for the development of late-onset Alzheimer’s disease. In healthy older adults, research suggests that carrying a copy of this gene can lead to a poorer performance on a variety of cognitive tasks. However, the relationship between APOE e4 and spatial memory in mid-age is ambiguous. Using a precision memory task, some studies find a short-term memory advantage for mid-aged e4 carriers , whilst others report no differences in long term retention between genotype groups . Often these studies have small sample sizes and larger studies tend to lack e4/e4 carriers. Here we aim to conduct an appropriately powered study to investigate a dose-dependent effect of e4 on spatial long-term memory and precision in mid-age healthy adults.
Over 300 APOE genotyped individuals were recruited through the NIHR BioResource to take part in our online study. Participants have a genotype of e3/e3, e3/e4 or e4/e4 so that we can investigate the dose-dependent effect of e4 on task performance. Participants completed an object-location memory task consisting of 75 trials split into five blocks of 5 scenes each containing three objects. The data has now been collected; however, we are currently blind to APOE genotype status until BioResource provide us with this information.
Using mixture modelling, we will build two models of object-location memory performance. These summary measures will then be entered into a mixed-effects analysis to test the effect of APOE status, age, and sex on memory performance. Across two sets of analyses, APOE status will be modelled as both a categorically coded genotype (e3/e3 vs e3/e4 vs e4/e4), and as a linear predictor specifying the number of e4 allele (0 vs 1 vs 2). Inferences will be informed by both frequentist and Bayesian statistics.
These planned analyses are being pre-registered before the data are unblinded.