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Sex-specific entorhinal cortex functional connectivity in cognitively normal older adults with amyloid-β pathology1Neurologu, Chengdu Second People's Hospital, Chengdu, China, 2Neurolog, The Third Affiliated Hospital of Anhui Medical University, Hefei, China
Synopsis
Keywords: Alzheimer's Disease, Alzheimer's Disease
Motivation: The sex-specific brain alteration in cognitively normal older adults with amyloid-β pathology was unclear.
Goal(s): This study aimed to investigate the impact of sex and APOE genotype on the functional connectivity of the entorhinal cortex (ERC) in cognitively normal older adults with amyloid-β pathology.
Approach: Using a large sample from the A4 study, the authors performed a comprehensive analysis comparing demographic information, cognitive performance, volumetric MRI data, and ERC functional connectivity.
Results: Results revealed sex-specific differences in ERC connectivity, with males showing higher connectivity in the sensorimotor network and females exhibiting higher connectivity in the default mode, executive control, and reward networks.
Impact: This study sheds light on the influence of sex and APOE genotype on the functional connectivity of the entorhinal cortex in cognitively normal older adults with amyloid-β pathology.
Aims
Sex and APOE genotype have been shown to influence the risk and progression of Alzheimer's disease (AD). The entorhinal cortex (ERC) is a brain region that plays a crucial role in memory and navigation 1 and is among the initial regions to exhibit pathological changes in AD 2. However, the impact of these factors on the functional connectivity of the ERC in cognitively normal older adults with amyloid-β (Aβ+) pathology remains unclear.Methods
A total of 1,022 cognitively normal older adults with Aβ+ (603 females, and 586 APOE ε4+) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were included in this study. The 2x2 (gender, 2 APOE genotypes) analysis of covariance was performed to compare the demographic information, cognitive performance, and volumetric MRI data among these groups. Voxel-wise comparisons of bilateral ERC functional connectivity (ERC-FC) were conducted, and partial correlation analyses were used to explore the associations between cognitive performance and ERC-FC strength.Results
We found that the APOE genotype influenced ERC functional connectivity mainly in the sensorimotor network (SMN). Males exhibited higher ERC-FC in the salience network (SN), while females displayed higher ERC-FC in the default mode network (DMN), executive control network (ECN), and reward network. The interplay of sex and APOE genotype on ERC-FC was observed in the SMN and cerebellar lobe. The ERC-FC was associated with executive function and memory performance in individuals with CUOA-Aβ+.Conclusion
Our findings provide evidence of sex-specific ERC functional connectivity compensation mechanism in cognitively normal older adults with Aβ+ pathology. This study may contribute to a better understanding of the mechanisms underlying the early stages of Alzheimer's disease and may help develop personalized interventions in preclinical AD.Acknowledgements
The A4 study is a secondary prevention trial in preclinical AD, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals.References
1. Fyhn M, Molden S, Witter MP, Moser EI, Moser M-B. Spatial representation in the entorhinal cortex. Science. 2004;305(5688):1258-64.
2. de Leon MJ, DeSanti S, Zinkowski R, Mehta PD, Pratico D, Segal S, et al. MRI and CSF studies in the early diagnosis of Alzheimer's disease. J Intern Med. 2004;256(3):205-23.
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