Recognition memory is associated with altered resting-state functional connectivity in people at genetic risk for Alzheimer's disease

The apolipoprotein E epsilon 4 (ApoE epsilon 4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE epsilon 4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80years old), of which 20 carried the epsilon 4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE epsilon 4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, epsilon 4 carriers showed increased connectivity relative to epsilon 4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in epsilon 4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing