Session Title: Alzheimer's Disease (AD) including Non-Cognitive Aspects
Presentation Date: Friday, March 14 – Saturday, March 15, 2009
DOPAMINE MODULATES ACETYLCHOLINE CORTICAL EXCITABILITYI IN ALZHEIMER'S PATIENTS
A. Martorana, F. Mori, H. Kusayanagi, F. Monteleone, Z. Esposito, G. Sancesario, G. Bernardi, G. Koch
Clinica Neurologica, Neuroscience, Rome, Italy
Objective: In AD patients dysfunction of cholinergic neurons is considered a typical hallmark, leading to rationale for the pharmacologic treatment in use based on drugs that enhance acetylcholine neurotransmission. Our recent work demonstrated that in AD patients the administration of L-Dopa determined consistent modification of cortical excitability similar to that demonstrated using cholinomimetics. In that work we hypothesized that the effects of L-Dopa could be explained either through a direct effect of dopamine on GABA interneurones of the cortex or through a direct effect on cholinergic neurons of the Meynert's basal nucleus.
Materials and methods: To do this we used a technique that was demonstrated to give information about the function of cholinergic circuits in human cerebral cortex. This test is based on coupling TMS with peripheral nerve stimulation. This effect is termed short latency afferent inhibition (SAI) of the motor cortex is produced by interactions within the cerebral cortex. Since this effect is abolished or reduced using cholinomimetics, it is considered a non invasive way to test cholinergic activity in the cerebral cortex (Di Lazzaro et al., 2002). In Alzheimer's disease patients SAI is reduced, and is modified by cholinergic drugs. In this work we tested the whether L-Dopa administration can modify SAI test in control and AD patients.
Results: Our results indicate that L-Dopa modifies cortical excitability in AD patients influencing SAI tes in Ad patients.
Conclusions: Dopamine can influence both acetylcholine release and cortical excitability in AD patients through different mechanisms that need to be further investigated.