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Preserved cholinergic forebrain structure reduces the impact of strategic lesions to the connectome in mild cognitive impairment
Author(s) -
Berlot Rok,
Koritnik Blaž,
Pirtošek Zvezdan,
Ray Nicola
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043882
Subject(s) - connectome , thalamus , neuroscience , hippocampus , tractography , nucleus basalis , medicine , cholinergic , atrophy , psychology , diffusion mri , basal forebrain , pathology , magnetic resonance imaging , functional connectivity , radiology
Background Undetected neurodegeneration is present in many patients with stroke. Clinical consequences of stroke might be partly determined by pre‐existing changes in brain structure. Cortical acetylcholine allows favourable adaptation to pathological changes within the limbic system. However, it remains unclear if it acts more broadly, affecting the configuration of the structural connectome. To test this, we aimed to assess the relationship between nucleus basalis of Meynert (NBM) structure and vulnerability of the connectome to simulated strategic lesions in patients with mild cognitive impairment (MCI). Method Twenty patients with MCI and 20 healthy elderly controls underwent 3T structural and diffusion‐weighted MRI. 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 measured as the proportional change in global efficiency of the connectome. Relationships between NBM volume, global efficiency of intact connectomes and impacts of individual simulated lesions of network nodes were assessed, controlling for demographic variables and atrophy of individual nodes. Result Artificial removal of the thalamus and the hippocampus from the connectome had a lower impact on global efficiency in MCI compared to controls. In MCI, NBM volume was correlated with global efficiency of intact connectomes. Higher NBM volumes were associated with reduced impact of thalamic lesions and lesions of the entorhinal and posterior cingulate cortices. These relationships were not present in other cortical or subcortical nodes or in controls. Conclusion Reduced vulnerability to damage of the hippocampus and thalamus in MCI suggests that connections essential for efficient network structure “shift” away from these areas. In MCI, preserved NBM is associated with efficient network topology and has a protective effect against the global impact of simulated strategic lesions. By influencing the configuration of the connectome in MCI, the cholinergic system might have a protective effect against the impact of targeted damage. Structural connectome alterations in response to early neurodegeneration represent a potential mechanism for synergy between neurodegeneration and vascular lesions in post‐stroke cognitive impairment and mixed dementia.