<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

Abstract

Aim: To test the association between cognitive performance and APOE genotype, and to assess potential modifications of this association by sociodemographic and neuroanatomical factors in a sample of 74 healthy elders. Methods: Firstly, we explored the isolated role of the APOE ɛ4 genotype (i.e., APOE4) in different neuropsychological tests, and then the effects of its interaction with sociodemographic (i.e., age, gender, and educational level) and neuroanatomical (i.e., hippocampal volumes) variables. Subsequently, we performed the same analyses after dividing the sample into two subgroups according to their Mini-Mental State Examination scores (control-high group ≥29 and control-low group < 29). Results: In the whole group, APOE4 carriers exhibited a significantly poorer execution in several cognitive domains including global cognitive functioning, episodic memory, verbal fluency, and naming. This effect was more noticeable in older and less educated subjects. The separated analyses revealed that APOE4 carriers in the control-low group exhibited lower scores in global cognitive functioning and episodic memory, while no effects were observed in the control-high group. Neither gender nor hippocampal volumes showed a significant interaction effect with APOE genotype. Conclusions: Current results point out that APOE4 genotype influences healthy aged cognition, although factors such age or educational attainment seem to modulate its effects.

Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum

“…More recently, Foster and coworkers [11] reported that, when the statistical methods removed the effects due to the inclusion of MCIs (considering them as prodromal AD cases), the significant influence of APOE4 vanished. A recent investigation by our group also reinforced the preclinical/prodromal assumption [12]. Inspired by Foster et al's study [11], we evaluated APOE4's effects on cognitive performance in a sample of healthy aged controls and observed that APOE4 carriers exhibited a significantly poorer performance on several cognitive domains, but such effect was explained by the group with a higher risk of presenting cognitive deterioration.…”

Gray Matter Densities in Limbic Areas and APOE4 Independently Predict Cognitive Decline in Normal Brain Aging

“…Cognitive variations in healthy elders within the normal range may be determined by demographic factors, basal cognition, and APOE genotyping that were not systematically taken into account in multivariate models. In fact, male gender, low level of education, and mainly the presence of APOE4 allele have been associated with worst cognitive trajectories in non-demented elders (Bretsky et al, 2003; Honea R. et al, 2009; Honea R. A. et al, 2009; Zehnder et al, 2009; Haller et al, 2017; Li et al, 2017; Lin et al, 2017) but negative or ambiguous data have also been reported (Van Gerven et al, 2012; López et al, 2017; Min, 2018). In the present study, higher MMSE scores are associated with higher risk of cognitive decline in this series.…”

Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV

“…The results of this study need to be interpreted in the light of several limitations. The results of several investigations into the genetic contributions to HAND suggest that the harmful effects of ApoE ε4 on cognitive function may be likely to be expressed at a later age (Valcour et al 2004;Pomara et al 2008;Panos et al 2013;Mukerji et al 2016;López et al 2017). Such a temporally mediated effect could explain some of the divergent literature findings regarding the role of ApoE in HAND.…”