APOE Effects on Default Mode Network in Chinese Cognitive Normal Elderly: Relationship with Clinical Cognitive Performance

Haiqing Song, Haixia Long, Xiumei Zuo, Chunshui Yu, Bing Liu, Zhiqun Wang, Qi Wang, Fen Wang, Ying Han, Jianping Jia, Haiqing Song, Haixia Long, Xiumei Zuo, Chunshui Yu, Bing Liu, Zhiqun Wang, Qi Wang, Fen Wang, Ying Han, Jianping Jia

Abstract

Background: Functional connectivity in default mode network (DMN) may be changed in Alzheimer's disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD.

Methods: Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers.

Results: Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region.

Conclusion: APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Significantly different DMN functional connectivity…
Fig 1. Significantly different DMN functional connectivity between APOE ε4ε3 and ε3ε3.
Brain model for the changed functional connectivity: the red line represented the increased functional connectivity in ε4ε3 carriers, and blue line represented the decreased one.
Fig 2. Changed functional connectivity was associated…
Fig 2. Changed functional connectivity was associated with cognitive performances.
A. The increased LPHC-R.Sup.F functional connectivity was positively correlated with the changes of delay recall from baseline to follow-up. B. The increased LPHC-vMPFC functional connectivity had a positive correlation with MMSE at baseline, and C. a negative correlation with long-delayed recognition at follow-up.
Fig 3. Whole brain functional connectivity by…
Fig 3. Whole brain functional connectivity by taking LPHC as a seed region.
Significantly increased functional connectivity presented in medial prefrontal cortex (cluster size = 20, p = 0.005) in APOE ε4 carriers were presented from different directions.

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