Apolipoprotein E ε4 accelerates the longitudinal cerebral atrophy in open access series of imaging studies-3 elders without dementia at enrollment

IntroductionEarly studies have reported that APOE is strongly associated with brain atrophy and cognitive decline among healthy elders and Alzheimer's disease (AD). However, previous research has not directly outlined the modulation of APOE on the trajectory of cerebral atrophy with aging during the conversion from cognitive normal (CN) to dementia (CN2D). MethodsThis study tried to elucidate this issue from a voxel-wise whole-brain perspective based on 416 qualified participants from a longitudinal OASIS-3 neuroimaging cohort. A voxel-wise linear mixed-effects model was applied for detecting cerebrum regions whose nonlinear atrophic trajectories were driven by AD conversion and to elucidate the effect of APOE variants on the cerebral atrophic trajectories during the process. ResultsWe found that CN2D participants had faster quadratically accelerated atrophy in bilateral hippocampi than persistent CN. Moreover, APOE epsilon 4 carriers had faster-accelerated atrophy in the left hippocampus than epsilon 4 noncarriers in both CN2D and persistent CN, and CN2D epsilon 4 carriers an noncarriers presented a faster atrophic speed than CN epsilon 4 carriers. These findings could be replicated in a sub-sample with a tough match in demographic information. DiscussionOur findings filled the gap that APOE epsilon 4 accelerates hippocampal atrophy and the conversion from normal cognition to dementia.

Automated summary

This study investigated the modulation of APOE on cerebral atrophy and its role in the conversion from cognitive normal (CN) to dementia using a voxel-wise whole-brain perspective. The results revealed that APOE epsilon 4 carriers showed faster-accelerated atrophy in the left hippocampus compared to noncarriers, and both CN2D epsilon 4 carriers and noncarriers exhibited a faster atrophic speed than CN epsilon 4 carriers. These findings were replicated in a sub-sample with strict demographic matching.