Preserved cholinergic forebrain integrity reduces structural connectome vulnerability in mild cognitive impairment

Abstract Neurodegeneration leads to redistribution of processing, which is reflected in a reorganisation of the structural connectome. This might affect its vulnerability to structural damage. Cortical acetylcholine allows favourable adaptation to pathology within the memory circuit. However, it remains unclear if it acts on a broader scale, affecting reconfiguration of whole-brain networks. To investigate the role of the cholinergic basal forebrain (CBFB) in strategic lesions, twenty patients with mild cognitive impairment (MCI) and twenty elderly controls underwent magnetic resonance imaging. Whole-brain tractograms were represented as network graphs. Lesions of individual nodes were simulated by removing a node and its connections from the graph. The impact of simulated lesions was quantified as the proportional change in global efficiency. Relationships between subregions CBFB volumes, global efficiency of intact connectomes and impacts of individual simulated lesions of network nodes were assessed. In MCI but not controls, larger CBFB volumes were associated with efficient network topology and reduced impact of hippocampal, thalamic and entorhinal lesions, indicating a protective effect against the global impact of simulated strategic lesions. This suggests that the cholinergic system shapes the configuration of the connectome, thereby reducing the impact of localised damage in MCI.