Cortical excitability in very mild Alzheimer’s disease: a long-term follow-up study

Abstract

Measurement of motor cortex excitability using paired-pulse transcranial magnetic stimulation (pTMS) has been proposed for the early diagnosis of Alzheimer's disease (AD) and could also be useful for monitoring treatment response and disease progression. However, studies conducted at the pre-dementia stage of AD are scarce, very few long-term data are available, and correlations between cortical excitability and cognitive performance have not been addressed. Eleven patients with mild cognitive impairment (MCI) that converted to AD-related dementia and 12 elderly control subjects were selected for this study. Cognitive assessments and pTMS were conducted at baseline in the two groups and also after 4 and 21 months of treatment with donepezil in the AD group. Non-parametric statistics were used to compare cortical excitability between the two study groups at baseline and to analyse disease course in the AD group. Correlation analysis was performed to investigate associations between cortical excitability and cognitive performance. Short-latency intracortical inhibition (SICI) and intracortical facilitation were reduced in AD patients. However, there was high inter-individual variability, and statistical significance was only attained at a 2-ms interstimulus interval (ISI). A trend towards recovery of 2-ms SICI was observed after treatment with donepezil. Baseline cortical excitability at 300 ms was associated with better cognitive performance in AD patients. Although the present results do not support a role for pTMS in the early diagnosis of late-onset AD, a potential role in prediction of treatment response and understanding of disease mechanisms emerged.

Reduced interhemispheric inhibition in mild cognitive impairment

“…No consistent result has been reported concerning the ICF. They concluded that SICI and ICF were not good tools for the diagnosis of early-stage AD (Olazarán et al 2010). In our patients, both SICI and ICF were normal; though SICI had a tendency to be reduced in MCI, SICI might be mildly reduced in MCI.…”

“…Some previous papers reported a reduction in SICI in early-onset AD (Pierantozzi et al 2004) and MCI converted to AD (Olazarán et al 2010) even though there was high interindividual variability. No consistent result has been reported concerning the ICF.…”

Intra- and inter-cortical motor excitability in Alzheimer’s disease

“…Furthermore, an impairment of the SICI has previously been found in AD patients (Di Lazzaro et al 2004;Pierantozzi et al 2004;Nardone et al 2006;Liepert et al 2001), possibly reflecting a dysregulation of the intracortical GABAergic inhibitory circuitries in AD patients (Nardone et al 2006). These effects could be modulated by acetylcholinesterase inhibitors (AchEI) (Pierantozzi et al 2004;Liepert et al 2001;Korchounov et al 2005;Olazaran et al 2010) and L-dopa (Martorana et al 2008). Mean MEP amplitude changes ((CS ?…”

Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial

“…Treatment-related changes in functional connectivity within frontal networks were significantly correlated with the increase in ABAS-II functional academic skills. Using non-invasive TMS, [17][18][19] we showed that EGCG and cognitive training normalised intracortical facilitation. We speculate that these effects could also contribute to the improved cognitive abilities in individuals treated with EGCG and cognitive training, since cognitive deficits in Down's syndrome have been proposed to result from an imbalance, with an excess of synaptic inhibition in the hippocampus and increased excitation in the cerebral cortex.…”