Episodic memory of APOE ε4 carriers is correlated with fractional anisotropy, but not cortical thickness, in the medial temporal lobe

The ε4 allele of apolipoprotein E (apoE, protein; APOE, gene) is the most important genetic risk factor for the development of Alzheimer's disease (AD). Cortical structures in the medial temporal lobe (MTL) are important for memory function and are affected early in AD. Both gray matter (GM) and white matter (WM) structures in the MTL have been reported to display AD related changes in healthy APOE ε4 carriers, but the effects are relatively small and somewhat deviating. Still, there is a lack of studies directly linking structural measures with performance on psychometric tests in ε4+ individuals. We hypothesized that intact WM integrity in the MTL facilitates episodic memory, and predicted a higher correlation between WM integrity and memory performance in APOE ε4 carriers due to a possible limiting effect of WM microstructure. In the present study of 92 healthy (MMSE>27) participants we acquired T1 3D and DTI images from a 1.5T MRI scanner, and tested the participants with California Verbal Learning Test II (CVLT-II). The study had two main aims: 1) to relate verbal memory performance to entorhinal WM (EWM) integrity in APOE ε4 carriers and non-carriers, and 2) to investigate APOE ε4 effects on EWM and EC thickness. We observed a strong, positive correlation between FA in the EWM and memory performance, which was driven solely by APOE ε4 carriers. These effects were significant while controlling for age, sex, EWM volume and EC thickness. Although EC thickness was significantly reduced in ε4 carriers, we did not find a relationship between EC thickness and memory performance. Thus, increased susceptibility of the WM structures underpinning the entorhinal-hippocampal network, offers a plausible explanation for the earlier onset of cognitive decline previously reported in APOE ε4 carriers.