TACRINE HYDROCHLORIDE IS A REVERSIBLE CHOLINESTERASE INHIBITOR. ALTHOUGH WIDESPREAD DEGENERATION OF MULTIPLE CNS NEURONAL SYSTEMS EVENTUALLY OCCURS, EARLY PATHOLOGICAL CHANGES IN ALZHEIMER'S DISEASE INVOLVE, IN A RELATIVELY SELECTIVE MANNER, CHOLINERGIC NEURONAL PATHWAYS THAT PROJECT FROM THE BASAL FOREBRAIN TO THE CEREBRAL CORTEX AND HIPPOCAMPUS. THE RESULTING DEFICIENCY OF CORTICAL ACETYLCHOLINE IS BELIEVED TO ACCOUNT FOR SOME OF THE CLINICAL MANIFESTATIONS OF MILD TO MODERATE DEMENTIA. TACRINE, AN ORALLY BIOAVAILABLE, CENTRALLY ACTIVE, REVERSIBLE CHOLINESTERASE INHIBITOR, PRESUMABLY ACTS BY ELEVATING ACETYLCHOLINE CONCENTRATIONS IN THE CEREBRAL CORTEX BY SLOWING THE DEGRADATION OF ACETYLCHOLINE RELEASED BY STILL INTACT CHOLINERGIC NEURONS. IF THIS THEORETICAL MECHANISM OF ACTION IS CORRECT, TACRINE'S EFFECTS MAY LESSEN AS THE DISEASE PROCESS ADVANCES AND FEWER CHOLINERGIC NEURONS REMAIN FUNCTIONALLY INTACT. THERE IS NO EVIDENCE THAT TACRINE ALTERS THE COURSE OF THE UNDERLYING DEMENTING PROCESS.