ASSOCIATION BETWEEN SHORT LATENCY AFFERENT INHIBITION AND STRUCTURE OF THE CHOLINERGIC SYSTEM IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

Abstract

Alzheimer's disease is a neurodegenerative disorder that involves degeneration of the cholinergic system in the basal forebrain (e.g. Grothe et al., 2010; Grothe, Heinsen, & Teipel, 2012; Kása, Rakonczay, & Gulya, 1997). Transcranial magnetic stimulation (TMS) protocols, like short latency afferent inhibition (SAI) of the motor cortex, can serve as a useful tool to depict cholinergic degeneration, as SAI is significantly reduced in AD (Di Lazzaro et al., 2002) as well as in patients with amnestic MCI (Nardone et al., 2012), which are at higher risk of developing AD. So far, no study has examined the association between SAI and the volume of the cholinergic system, nor has found an association between SAI and global cognitive abilities, although negative correlations were found between SAI and delayed verbal recall (Nardone et al., 2012). So far, 18 healthy controls and 10 patients with MCI underwent a global cognitive assessment (Montreal Cognitive Assessment battery, MoCA; Nasreddine et al., 2005) as well as magnetic resonance imaging (MRI) and TMS using the SAI protocol described by Tokimura (2000). Grey matter volumes of the basal forebrain cholinergic system (BFCS; CH 1-4) were extracted using SPM 12 (FIL Methods Group, University College London, UK). Partial correlations between SAI and cholinergic system variables were computed by removing the effects of hippocampus volume to test the specificity of identified correlations. Mean SAI and structural cholinergic system variables were reduced in patients with MCI compared to healthy controls. SAI was negatively correlated with volume of the BFCS in healthy controls and patients with MCI. There was a negative correlation between SAI and total MoCA scores in healthy controls. Conversely, a positive correlation was found between MoCA total score and BFCS in patients with MCI. The reduced SAI-values and the reduced volumes of the cholinergic system provide evidence of cholinergic dysfunction among patients with MCI. Findings indicate that volumetry of the cholinergic system is independent from hippocampus atrophy and related to functional markers of the cholinergic system such as SAI.