%0 Journal Article
%A Fernández Lucas, Alberto Amable
%A Vaquero Zamora, Lucía
%A Bajo Bretón, Ricardo
%A Zuluaga Arias, María del Pilar
%T Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum
%D 2022
%@ 2509-2715
%U https://hdl.handle.net/20.500.14352/71324
%X Whether the deleterious efects of APOE4 are restricted to the Alzheimer’s disease (AD) spectrum or cause cognitive impairment irrespectively of the development of AD is still a matter of debate, and the focus of this study. Our analyses included APOE4 genotype, neuropsychological variables, amyloid-βeta (Aβ) and Tau markers, FDG-PET values, and hippocampal volumetry data derived from the healthy controls sample of the ADNI database. We formed 4 groups of equal size (n=30) based on APOE4 carriage and amyloid-PET status. Baseline and followup (i.e., 48  months post-baseline) results indicated that Aβ-positivity was the most important factor to explain poorer cognitive performance, while APOE4 only exerted a signifcant efect in Aβ-positive subjects. Additionally, multiple regression analyses evidenced that, within the Aβ-positive sample, hippocampal volumetry explained most of the variability in cognitive performance for APOE4 carriers. These fndings represent a strong support for the so-called preclinical/prodromal hypothesis, which states that the reported diferences in cognitive performance between healthy carriers and non-carriers are mainly due to the APOE4’s capability to increase the risk of AD. Moreover, our results reinforce the notion that a synergistic interaction of Aβ and APOE4 elicits a neurodegenerative process in the hippocampus that might be the main cause of impaired cognitive performance.
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