Effects of the apolipoprotein E ε4 allele on functional MRI during n-back working memory tasks in healthy middle-aged adults

Abstract

Background and purpose: APOE4 is the best-documented genetic risk factor for sporadic AD. Previous research showed that APOE4 is associated with increased risk of occurrence and earlier onset of AD in a gene dose-dependent manner. However, the specific role of APOE4 in processing of brain functions requires further investigation. Investigators have used fMRI to measure brain activity on the basis of the blood oxygen level-dependent contrast. This study investigates the effects of APOE4 on fMRI during n-back WM tasks in healthy middle-aged adults.

Materials and methods: From 110 participants, 81 individuals without objective or subjective cognitive impairment underwent APOE genotyping. Nine APOE4 carriers and 9 age- and sex-matched non-APOE4 controls were recruited for fMRI examinations during WM tasks.

Results: Both groups displayed increased brain activation in response to increases in WM loads. During low-WM-load tasks, the APOE4 carriers recruited significantly greater additional processing resources than the non-APOE4 carriers. During moderate- and high-WM-load tasks, the APOE4 carrier group displayed fewer increases in activation than the non-APOE4 carrier group.

Conclusions: APOE genetic polymorphisms may affect brain functioning in subjects without dementia. The patterns of brain activation during different levels of WM load suggest possible subclinical impairment of WM capacity in APOE4 carriers (ClinicalTrials.gov registration: NCT01287819).

Figures

Fig 1.

Activation maps of n-back task of APOE4 carriers and non-APOE4 carriers in a surface-rendered projection displayed on a standardized brain atlas (display threshold, P < .01; extent, 3 voxels). Increased activation in bilateral frontal and parietal regions is noted, consistent with activation of WM circuitry in both groups.

Fig 2.

Activation maps of 1-back > 0-back, 2-back > 1-back, and 3-back > 2-back conditions of APOE4 carriers and non-APOE4 carriers in a surface-rendered projection displayed on a standardized brain atlas (display threshold, P < .01; extent, 3 voxels). In both groups, an increase in brain activation occurred in response to each increase in WM load. The degree of increased brain activation was different in both groups. It was greatest in 2-back > 1-back conditions in non-APOE4 carriers, and greatest in 1-back > 0-back conditions in APOE4 carriers. A visual comparison of the between-group difference in 1-back > 0-back conditions shows less extent of activation in the noncarrier group. In 2-back 1-back and 3-back > 2-back conditions, less increase in activation is seen in the carrier group.