RESUMO
Resting-state functional magnetic resonance imaging measures pathological alterations in neurodegenerative diseases, including Alzheimer's disease. Disruption in functional connectivity may be a potential biomarker of ageing and early brain changes associated with AD-related genes, such as APOE and BDNF. The objective of this study was to identify group differences in resting-state networks between individuals with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons. Dual regression following Independent Components Analysis were performed to examine differences associated with these polymorphisms. APOE ε3 homozygotes showed stronger functional connectivity than APOE ε4 carriers. Males showed stronger functional connectivity between the Default Mode Network (DMN) and grey matter premotor cortex, while females showed stronger functional connectivity between the executive network and lateral occipital cortex and parahippocampal gyrus. Additionally, we found that with increasing cognitive reserve, functional connectivity increased within the Dorsal Attention Network (DAN), but decreased within the DMN. Interaction effects indicated stronger functional connectivity in Met/ε3 carriers than in Met/ε4 and Val/ε4 within both the DMN and DAN. APOE/BDNF interactions may therefore influence the integrity of functional brain connections in older adults, and may underlie a vulnerable phenotype for subsequent Alzheimer's-type dementia.
Assuntos
Apolipoproteína E3/genética , Apolipoproteína E4/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Encéfalo/fisiologia , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Magnetic resonance imaging (MRI) offers significant insight into the complex organization of neural networks within the human brain. Using resting-state functional MRI data, topological maps can be created to visualize changes in brain activity, as well as to represent and assess the structural and functional connections between different brain regions. Crucially, Alzheimer's disease (AD) is associated with progressive loss in this connectivity, which is particularly evident within the default mode network. In this paper, we review the recent literature on how factors that are associated with risk of dementia may influence the organization of the brain network structures. In particular, we focus on cognitive reserve and the common genetic polymorphisms of APOE and BDNF Val66Met.
