Abstract
Whether the deleterious effects 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 follow-up (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 significant effect 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 findings represent a strong support for the so-called preclinical/prodromal hypothesis, which states that the reported differences 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.
Original language | English (US) |
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Pages (from-to) | 195-209 |
Number of pages | 15 |
Journal | GeroScience |
Volume | 44 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2022 |
Keywords
- Amyloid markers
- ApoE4
- Cognitive deterioration
- Cognitive phenotype
- Healthy aging
- Preclinical and prodromal Alzheimer’s disease
ASJC Scopus subject areas
- Aging
- veterinary (miscalleneous)
- Complementary and alternative medicine
- Geriatrics and Gerontology
- Cardiology and Cardiovascular Medicine