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.
Martorana
Alessandro
A
Dipartimento di Neuroscienze, Clinica Neurologica, Università di Roma, "Tor Vergata", via Montpellier, 1, 00133 Rome, Italy, martorana@med.uniroma2.it
Stefani
Alessandro
A
Palmieri
Maria Giuseppina
MG
Esposito
Zaira
Z
Bernardi
Giorgio
G
Sancesario
Giuseppe
G
Pierantozzi
Mariangela
M
D000109:Acetylcholine / Q000378:metabolism; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D018678:Cholinergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018697:Nootropic Agents / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation
D018678:Cholinergic Agents; D015259:Dopamine Agents; D018697:Nootropic Agents; D007980:Levodopa; C035420:levodopa methyl ester; D000109:Acetylcholine; D004298:Dopamine