The Effect of Apolipoprotein E ɛ4 (APOE E4) on Visuospatial Working Memory in Healthy Elders and Amnestic Mild Cognitive Impairment Patients: An Event-related Potentials Study

Abstract

Introduction

Previous studies provided inconsistent evidences for the effect of apolipoprotein E ɛ4 (APOE ɛ4) status on the visuospatial working memory (VSWM). Our study was the first investigation with event-related potential (ERP) to explore the effect of APOE ɛ4 on VSWM in healthy elders and aMCI patients.

Objective

The aim was to investigate the effect of APOE ɛ4 on VSWM with event-related potential (ERP) study in healthy elders and aMCI patients.

Methods

Thirty-nine aMCI patients (27 APOE ɛ4 non-carriers and 12 APOE ɛ4 carriers) and 43 their matched control (25 APOE ɛ4 non-carriers and 18 APOE ɛ4 carriers) performed an N-back task, a VSWM paradigm that manipulated the number of items to be stored in memory.

Results

Our study detected reduced accuracy and delayed mean correct response time in aMCI patients than healthy elders. P300 was elicited by VSWM and its amplitude was lower in aMCI patients at the central-parietal and parietal electrodes than healthy controls. In healthy elders, P300 amplitude declined prior to task performance change in APOE ɛ4 carriers than non-carriers. Regarding aMCI patients, P300 amplitude result revealed exacerbated VSWM deficits in APOE ɛ4 carriers than APOE ɛ4 non-carriers. Additionally, standardized low-resolution brain electromagnetic tomography analysis (s-LORETA) result showed enhanced brain activation in right parahippocampal gyrus during P300 time range in APOE ɛ4 carriers than non-carriers in aMCI patients (Fig. 1, Tables 1 and 2).

Conclusions

It demonstrated that P300 amplitude might serve as a biomarker for recognizing aMCI patients and contribute to early detection of worse VSWM in APOE ɛ4 carriers than non-carriers.

Disclosure of interest

The author has not supplied his/her declaration of competing interest.

Fig. 1 The sLORETA images showing statistical differences between aMCI– APOE ɛ4− and aMCI– APOE ɛ4+ group (3D-view and slice-view) in the P300 time-range. The three slice-view images below located the maximal difference between aMCI– APOE ɛ4− and aMCI– APOE ɛ4+ group (MNI coordinates x, y, z = 10, −35, 0). Negative difference was in blue color with reference of aMCI– APOE ɛ4+ group Abbreviations: aMCI: amnestic mild cognitive impairement; APOE: apoliprotein E; MNI: Montreal Neurological Institute; sLoreta: standardized low-resolution brain electromagnetic tomography analysis.

Table 1 Behavioral data (accuracy and response time) for healthy controls and a MCI patients with different APOE ɛ4 status.

Data are presented as mean ± standard deviation (SD). aMCI: amnestic mild cognitive impairement; APOE: apoliprotein E; HC: healthy controls.

^aPost-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, HC-APOE ɛ4−vs. aMCI-APOE ɛ4−).

^bPost-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, HC-APOE ɛ4+vs. aMCI-APOE ɛ4+).

Table 2 ERP data (P300 amplitude) for healthy controls and aMCI patients with different APOE ɛ4 status.

Data are presented as mean ± standard deviation (SD); aMCI: amnestic mild cognitive impairement; APOE: apoliprotein E; HC: healthy controls.

^aPost-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, HC-APOE ɛ4− vs. HC-APOE ɛ4+).

^b Post-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, aMCI-APOE ɛ4− vs. aMCI-APOE ɛ4+).

^cPost-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, aMCI-APOE ɛ4− vs. HC-APOE ɛ4−).

^dPost-hoc tests by Bonferroni's analysis further revealed the source of ANCOVA difference (P < 0.05, aMCI-APOE ɛ4+ vs. HC-APOE ɛ4+).