Brain network analysis in Alzheimer’s disease and mild cognitive impairment using high-density diffuse optical tomography

Dementia is associated with altered resting- state connectivity, measures of which could aid in its early detection and monitoring. High- density diffuse optical tomography (HD- DOT) is well suited to detect these alterations at scale due to its numerous practical advantages, but it has not yet been applied to dementia. In this study, we investigated resting- state functional connectivity across the prefrontal cortex in individuals with mild cognitive impairment (MCI, n = 22), Alzheimer’s disease (AD, n = 21), and in healthy controls (n = 22). A graph theoretical approach was taken to characterise both global and local patterns of prefrontal connectivity over a 5- minute resting period. We found that individuals with MCI exhibited denser and stronger networks with shorter path lengths, which normalised in AD, accompanied by a redistribution of network hubs that were less stable. These results perhaps reflect the recruitment of additional connections in the early stages of pathology to maintain short- term network stability, which is ultimately associated with less efficient and more fragmented network organisation in later stages. Following the demonstration of HD- DOT’s capacity to detect differences between healthy ageing and AD- type cognitive impairment, this work opens up new possibilities for the use of optical imaging in the study of this clinical population and HD- DOT’s potential for scalable clinical use.