Shady Rahayel, Rémi Goupil, Dominique Suzanne Genest, Florence Lamarche, Mohsen Agharazii, Violette Ayral, Christina Tremblay, François Madore
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引用次数: 0
Abstract
Introduction: Chronic kidney disease (CKD) is associated with cognitive decline and changes in brain structure. However, their associations remain unclear, particularly the selective vulnerability characteristics that make some brain regions more vulnerable.
Methods: We investigated the baseline association between estimated glomerular filtration rates (eGFR) and cognitive function in 15,897 individuals from the CARTaGENE cohort. We performed vertex-based magnetic resonance imaging (MRI) analyses between eGFR and longitudinal cortical thickness in the 1397 participants who underwent brain MRI after 6 years. Imaging transcriptomics was used to characterize the gene expression and neurodegenerative features associated with this association.
Results: Lower eGFR correlated with reduced cognitive performance and brain structure. Brain regions associated with eGFR were enriched for mitochondrial and inflammatory-related genes. These associations occurred independently from age, sex, education, and body mass index (BMI), Framingham risk score, and white matter lesion volume.
Discussion: This study highlights the link between reduced eGFR, cognitive impairment, and brain structure, revealing some of the kidney-brain axis mechanisms.
Highlights: Lower eGFR is associated with reduced cognitive abilities.Structural brain changes are mediated by eGFR levels.Specific gene expression patterns correlate with lower eGFR and brain changes.Mitochondrial and inflammation-related genes were enriched in these patterns.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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