Age-Related Effect of APOE Genotype on Brain Functional Connectivity during Episodic Memory Encoding (P03.084)

Abstract

Objective: To determine the effect of APOE genotype on task-related connectivity in a sample of healthy individuals with ages spanning adulthood. Background The apolipoprotein E (APOE) e4 allele confers the highest genetic risk for Alzheimer9s disease. Recently, we discovered that healthy individuals carrying this genotype do not show the age-related decrease in medial temporal lobe (MTL) activation with memory tasks found in non carriers (Nichols et al., 2010), raising the speculation that functional connectivity with aging may also differ among APOE genotypes. Design/Methods: Right-handed healthy Caucasian volunteers (n=188) were genotyped and underwent 3T BOLD fMRI during visual scene encoding. β images were analyzed using a psychophysiological interaction (PPI) analysis implemented in SPM5. PPI with the entire brain was obtained from seed regions in the DLPFC, anterior and posterior hippocampi, and parahippocampal gyri of both hemispheres. Only p Results: The three APOE genotype groups studied (e2/3, n=27; e3/3, n=117 and e3/4, n=44) did not differ statistically in age (34±13, 31.6±11, and 32.4±12 years) sex (62, 59, and 59 percent women) or performance. PPI connectivity of the left DLPFC with the left posterior parahippocampus and of the right anterior hippocampus with the right DLPFC increased with aging in the e4 carriers, but not in the other two genotypes. The opposite relationship (fronto-MTL PPI connectivity tending to decrease with aging in the e4 carriers as compared to the other two genotypes) was not found even at a trend level in fronto-temporal networks. Conclusions: Our findings support the hypothesis that e4 carriers have increased fronto-MTL PPI connectivity with aging and are in agreement with studies showing greater resting MTL connectivity in old e4 carriers (Westlye et al., 2011; Filippini et al., 2009). Increased PPI connectivity in the context of adequate task performance may reflect compensation for a less efficient neural substrate in aging e4 carriers. Supported by: Intramural Research Program of the National Institutes of Health. Disclosure: Dr. Masdeu has received personal compensation in an editorial capacity for the Journal of Neuroimaging. Dr. Mattay has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Kohn has nothing to disclose. Dr. Muse has nothing to disclose. Dr. Kolachana has nothing to disclose. Dr. Nichols has nothing to disclose. Dr. Weinberger has nothing to disclose. Dr. Berman has nothing to disclose.