Kucikova, L. orcid.org/0000-0002-0769-9542, Zeng, J., Muñoz-Neira, C. et al. (6 more authors) (2023) Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals. Journal of Neurology, 270. pp. 4949-4958. ISSN 0340-5354
Abstract
Background
Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition.
Methods
We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task.
Results
The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions.
Conclusions
Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Alzheimer’s disease; Cognition; Functional connectivity; Functional neuroimaging; Large-scale networks; Risk factors |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Funding Information: | Funder Grant number Alzheimer’s Research UK ARUK-SRF2017B-1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Sep 2023 08:50 |
Last Modified: | 27 Sep 2023 08:52 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1007/s00415-023-11809-9 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:203646 |