Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/164534
Title: Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer's disease continuum
Authors: Ng, Kok Pin
Qian, Xing
Ng, Kwun Kei
Ji, Fang
Rosa-Neto, Pedro
Gauthier, Serge
Kandiah, Nagaendran
Zhou, Helen Juan
Keywords: Science::Medicine
Issue Date: 2022
Source: Ng, K. P., Qian, X., Ng, K. K., Ji, F., Rosa-Neto, P., Gauthier, S., Kandiah, N. & Zhou, H. J. (2022). Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer's disease continuum. ELife, 11, e77745-. https://dx.doi.org/10.7554/eLife.77745
Project: MOHCNIG18may-0003 
Journal: eLife 
Abstract: Background: Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organisation and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship. Methods: Seven hundred and eight participants from the Alzheimer’s Disease Neuroimaging Initiative were studied. Individual-level structural and metabolic covariance scores in higher-level cognitive and hippocampal networks were derived from magnetic resonance imaging and [18F] fluorodeoxyglucose positron emission tomography using seed-based partial least square analyses. The non-linear associations between network scores and memory across cognitive stages in each pathology group were examined using sparse varying coefficient modelling. Results: We showed that the associations of memory with structural and metabolic networks in the hippocampal and default mode regions exhibited pathology-dependent differential trajectories across cognitive stages using sparse varying coefficient modelling. In amyloid pathology group, there was an early influence of hippocampal structural network deterioration on memory impairment in the preclinical stage, and a biphasic influence of the angular gyrus-seeded default mode metabolic network on memory in both preclinical and dementia stages. In non-amyloid pathology groups, in contrast, the trajectory of the hippocampus-memory association was opposite and weaker overall, while no metabolism covariance networks were related to memory. Key findings were replicated in a larger cohort of 1280 participants. Conclusions: Our findings highlight potential windows of early intervention targeting network breakdown at the preclinical AD stage.
URI: https://hdl.handle.net/10356/164534
ISSN: 2050-084X
DOI: 10.7554/eLife.77745
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National Neuroscience Institute
Duke-NUS Medical School
Rights: © Ng, Qian et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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