L-dopa modulates motor cortex excitability in Alzheimer's disease patients

In Alzheimer's disease (AD), transcranial magnetic stimulation (TMS) studies have shown abnormalities of motor cortical excitability, such as a decreased intra-cortical inhibition (ICI) and changes in resting motor threshold (rMT). We studied the effects of L-dopa on rMT and ICI in a cohort of moderate AD patients after paired-pulse TMS. Results were compared with a control group of healthy subjects. As expected, AD patients showed a significant reduction in ICI and a lower rMT. L-dopa administration (soluble form, melevodopa 200 mg) promptly reversed the ICI impairment up to normalization. This effect was specific, since it was not mimicked in control subjects. These results indicate a possible role of dopamine in modulating AD cortical excitability, thus suggesting an interaction between dopaminergic ascending pathways and endogenous intracortical transmitters. In addition, considering that L-dopa showed a pharmacological profile similar to the one of cholinomimetics, L-dopa might represent a reliable tool to study new therapeutic perspective and strategies for AD.