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.

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.

Background Language is a crucial function that is preserved in healthy ageing. Broca’s and Wernicke’s area are known to be parts of the language network associated with speech production and comprehension, respectively. Pathological alterations that are identified in Alzheimer’s disease (AD) can be assessed using resting‐state fMRI. In particular, levels of oxygen in blood flow is measured as a proxy marker of brain activity. Functional connectivity with the Broca’s and Wernicke’s areas may be potential biomarkers of early brain changes associated with AD‐related genes, such as APOE and BDNF. Therefore, the objective of this study was to investigate age‐related differences in functional connectivity in the language networks (Broca’s and Wernicke’s area) associated with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons (n = 76). Method Data was pre‐processed using FSL. First level MELODIC (motion correction, brain extraction, and high‐pass filtering (100)) was applied for each dataset using Independent Components Analysis (ICA). Seed‐based correlation analysis was performed to investigate functional connectivity between the regions of interest and the rest of the brain. Result There were no significant differences in functional connectivity between the seed regions and other regions for APOE or BDNF (adjusted for age), but in a model with APOE + BDNF, age was positively correlated with functional connectivity between left Broca’s area and left frontal gyrus p = .003, as well between Wernicke’s area and right putamen and right supramarginal gyrus p = 0.02. Significant interactions indicating stronger functional connectivity in Met/ε3 than Met/ε4, p = 0.007, in Met/ε3 than in Val/ε3, p < .0001, and in Val/ε3 than Val/ε4 carriers, p < .0001, between the language networks and various brain regions, such as pre‐ & postcentral gyrus, parahippocampal gyrus, and precuneus. Conclusion These finding suggest that the degree to which the language network is interconnected may be associated with genetic interactions in the absence of clinical signs of disease. Disconnections within the functional language network may contribute to the loss of speech and comprehension in Alzheimer’s disease.