Subtle alterations in cerebrovascular reactivity in mild cognitive impairment detected by graph theoretical analysis and not by the standard approach

There is growing support that cerebrovascular reactivity (CVR) in response to a vasodilatory challenge, also defined as the cerebrovascular reserve, is reduced in Alzheimer's disease dementia. However, this is less clear in patients with mild cognitive impairment (MCI). The current standard analysis may not reflect subtle abnormalities in CVR. In this study, we aimed to investigate vasodilatory-induced changes in the topology of the cerebral blood flow correlation (CBF(corr)) network to study possible network-related CVR abnormalities in MCI. For this purpose, four CBF(corr) networks were constructed: two using CBF SPECT data at baseline and under the vasodilatory challenge of acetazolamide (ACZ), obtained from a group of 26 MCI patients; and two equivalent networks from a group of 26 matched cognitively normal controls. The mean strength of association (SA) and clustering coefficient (C) were used to evaluate ACZ-induced changes on the topology of CBF(corr) networks. We found that cognitively normal adults and MCI patients show different patterns of C and SA changes. The observed differences included the medial prefrontal cortices and inferior parietal lobe, which represent areas involved in MCI's cognitive dysfunction. In contrast, no substantial differences were detected by standard CVR analysis. These results suggest that graph theoretical analysis of ACZ-induced changes in the topology of the CBF(corr) networks allows the identification of subtle network-related CVR alterations in MCI, which couldn't be detected by the standard approach.