Background: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). Methods: We used transcranial magnetic stimulation to measure the active cortical motor threshold (ACMT) in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could have a direct effect on the excitability of the motor cortex. Results: An increase of the ACMT was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the threshold did not differ significantly from normal subjects. Conclusions: The results suggest an early functional impairment of cholinergic neurotransmission in AD, which is associated to early changes in the excitability of the motor system.

Background: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). Patients and Methods: We measured the silent period (SP) induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. Results: An increase in the duration of the SP was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the duration did not differ significantly from that of normal subjects. The results of our study show a fragmentation and an enlargement of the SP in the presence of multiple late excitatory potentials (LEPs) in early untreated AD patients. These LEPs were also modulated by donepezil. Conclusions: The results suggest an early functional impairment of cholinergic neurotransmission in AD. The disturbance in acetylcholine output in early AD leads to a decrease in excitability of the motor system.