title: Dopaminergic modulation of cortical plasticity in Alzheimer's disease patients.
abstract: In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are impaired. In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to be preserved. Dopaminergic transmission has been hypothesized as a new player in ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether administration of the dopamine agonist rotigotine (RTG) could modulate cortical plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols of repetitive transcranial stimulation applied over the primary motor cortex. Thirty mild AD patients were tested in three different groups before and after 4 weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent inhibition (SAI) protocol was performed to indirectly assess central cholinergic activity. A group of age-matched healthy controls was recruited for baseline comparisons. Results showed that at baseline, AD patients were characterized by impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels of LTP-like cortical plasticity were increased and normalized after RTG administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical plasticity was not modulated in any condition. Cholinergic activity was increased by both RTG and RVT. Our findings reveal that dopamine agonists may restore the altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing novel implications for therapies based on dopaminergic stimulation.
authors.affiliation: 1] Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy [2] Department of Neuroscience, Tor Vergata University, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Koch
authors.affiliation: 1] Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy [2] Department of Neuroscience, Tor Vergata University, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Lorenzo
authors.affiliation: Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonnì
authors.affiliation: Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Viola
authors.initials: V
authors.lastname: Giacobbe
authors.affiliation: Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.affiliation: 1] Non Invasive Brain Stimulation Unit, Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy [2] Department of Neuroscience, Tor Vergata University, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Neuroscience, Tor Vergata University, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D048448:Phenylcarbamates / Q000494:pharmacology; D000068836:Rivastigmine; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D002800:Cholinesterase Inhibitors; D018491:Dopamine Agonists; D048448:Phenylcarbamates; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D000068836:Rivastigmine