In vivo probe of central cholinergic systems

Age-related cognitive impairments and dementia of Alzheimer type have been linked to alterations in the cholinergic system. In the present study, evoked potentials and neuropsychological testing were obtained in healthy subjects during neuropharmacological manipulations including: scopolamine (anticholinergic), scopolamine plus physostigmine (anticholinesterase), scopolamine plus methylphenidate (adrenergic), and placebo. Scopolamine prolonged P3 latency and reduced spectral power of long latency evoked potentials without significantly altering earlier components. Physostigmine partially reversed these effects, but methylphenidate did not. Motor speed was slowed by scopolamine, but not by scopolamine plus methylphenidate. Cholinergic systems appear to be involved in generation or modulation of the P3 potential, possibly secondary to the cholinergic role in selective attention. Similar techniques may be useful as in vivo probes of central cholinergic function and thus as research and diagnostic aids in aging and disease.