115. D2 agonist administration restores altered cortical plasticity in Alzheimer’s disease patients

Abstract

LTP (Long-Term-Depression)-like cortical plasticity in Alzheimer disease (AD) patients is impaired. The dopamine involvement in controlling cortical plasticity in AD is still debated. We aimed at investigating whether administration of a D2 agonist could modulate cortical plasticity in AD, as measured by theta burst stimulation (TBS) protocols applied over primary motor cortex. Three groups of mild AD patients were tested before and after four weeks of treatment with rotigotine, rivastigmine or placebo. Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS (cTBS). Central cholinergic activity was evaluated by means of short latency afferent inhibition (SLAI) protocol. Neuropsychological evaluations were performed to assess cognitive functions. At baseline AD patients showed the previously described pattern of impaired LTP-like cortical plasticity. After four weeks of D2 agonist administration we observed a remarkable change in the LTP-like plasticity. Cholinergic activity was increased by both rotigotine and rivastigmine groups. Neuropsychological testing showed an improvement in the MMSE and in executive functions. Our findings highlight a role for dopamine in AD pathophysiology suggesting that a dysfunction of D2-like receptors is involved in mechanisms of altered cortical plasticity and providing implications for new therapies based on dopaminergic stimulation.