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 duringWMtasks. RESULTS: Both groups displayed increased brain activation in response to increases inWMloads. 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).
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