Specificity of brain activation patterns in people at genetic risk for Alzheimer disease.

Previous studies with positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI) have indicated differences in neural metabolism and activity between carriers of the APOE epsilon4 allele and those who are not at risk for Alzheimer disease (AD). Persons without dementia carrying the epsilon4 allele showed greater magnitude and extent of brain activation than noncarriers in regions required for memory, suggesting they performed additional cognitive work to accomplish the same task. To determine whether the fMRI differences were specific to a memory task or generalizable to any difficult cognitive task, the authors performed fMRI and compared images from 25 subjects with and without the APOE epsilon4 allele. In the most difficult conditions, all subjects showed increased MR signal in the prefrontal cortex, indicating increased cognitive effort. However, the two genetic groups showed no differences in activation patterns even at the most difficult task level, suggesting that additional cognitive effort in persons at genetic risk for AD is specific to episodic encoding and is not merely a reflection of task difficulty.