Hippocampal connectivity and memory decline in cognitively intact APOE ε4 carriers

INTRODUCTIONResting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment. METHODSCognitively normal apolipoprotein E (APOE) epsilon 4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers. RESULTSSteepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE epsilon 4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings. DISCUSSIONFindings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE epsilon 4 carriers before symptoms of mild cognitive impairment are present. HighlightsGraph theory connectivity detects preclinical hippocampal changes in APOE epsilon 4 carriers.The AD disconnection hypothesis was supported in unimpaired APOE epsilon 4 carriers.Hippocampal dysfunction starts asymmetrically on the left.

Automated summary

Resting-state fMRI graph theory can detect subtle functional connectivity changes affecting memory before impairment. This study compared the relationship between left/right hippocampal connectivity and memory trajectory in cognitively normal APOE ε4 carriers/noncarriers. The results showed that steep decline in verbal memory was correlated with decreased connectivity in the left hippocampus among APOE ε4 carriers, while there were no significant correlations in noncarriers. Verbal memory decline was also correlated with left hippocampal volume loss for both carriers and noncarriers.