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Neurology. 2005 Feb 8;64(3):501-8.

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

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University of California San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.



To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults.


Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions.


Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated.


The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.

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