Cholinergic circuitry functioning in patients with vascular cognitive impairment - No dementia

Background: An impairment of central cholinergic activity, as evaluated non-invasively by the shortlatency afferent inhibition (SAI) of motor responses evoked by transcranial magnetic stimulation (TMS), was observed in patients with Alzheimer’s disease (AD) and amnestic Mild Cognitive Impairment. Conversely, the involvement of central cholinergic neurotransmission in vascular dementia (VaD) is still under debate and data on Vascular Cognitive Impairment – No Dementia (VCI–ND) at risk for future VaD are lacking. Objective: To test for the first time SAI in patients with VCI–ND. Methods: Single-pulse TMS measures of cortical excitability and SAI were evaluated in 25 VCI–ND patients with subcortical ischemic lesions and 20 age-matched healthy controls. Functional status, neuropsychological tests evaluating frontal lobe abilities, and white matter lesions (WMLs) load were assessed. Results: A significant difference was found between patients and controls for the mean SAI, although this result did not resist after the Bonferroni correction. In the whole group of patients and controls, SAI showed a correlation with worse scores at the Montreal Cognitive Assessment (r = 0.376, p < 0.01). SAI also positively correlated with the total vascular burden (r = 0.345, p < 0.05) but not with the WML severity. Conclusions: Central cholinergic pathway does not seem to be involved in VCI–ND, and the current results differ from those reported in primary cholinergic forms of dementia, such as AD. SAI might represent a valuable additional tool in the differential diagnosis of the dementing processes and in identifying potential responders to cholinergic agents.