The effects of ApoE epsilon4 alleles on cognitive function and resting-state functional MRI in patients with amnestic mild cognitive impairment: a prospective cohort study
10.3760/cma.j.issn.1005-1201.2020.01.003
- VernacularTitle: ApoE-ε4等位基因对遗忘型轻度认知障碍患者认知功能及静息态功能MRI影响的前瞻性队列研究
- Author:
Xiaoni WANG
1
;
Yu SUN
1
;
Guanqun CHEN
1
;
Can SHENG
1
;
Xuanyu LI
1
;
Yuxia LI
1
;
Wenying DU
1
;
Xiaoqi WANG
1
;
Mingrui XIA
2
;
Ying HAN
3
Author Information
1. Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
2. State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Normai University, Beijing 100875, China
3. Department of Neurology, Xuanwu Hospital of Capital Medical University, Center of Alzheimer Disease, Beijing Institute for Brain Disorders, National Clinical Research Center for Geriatric Disorders, National Clinical Research Center for Geriatric Disorders (Xuanwu Hospital)-Alliance for Preclinical Alzheimer Disease in China, Beijing 100053, China
- Publication Type:Journal Article
- Keywords:
Alzheimer disease;
Cognition disorders;
Apolipoprotein E3;
Magnetic resonance imaging;
Neural networks (computer)
- From:
Chinese Journal of Radiology
2020;54(1):10-16
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study.
Methods:An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect.
Results:(1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ2=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm3, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm3, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC (F=10.833, P=0.002)as well as the left mPFC (F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory (r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers (r=-0.198, P=0.417) and the integration effect was significant (F=8.632, P=0.006).
Conclusions:The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.
