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.