Possible biochemical basis of memory disorder in Alzheimer disease.

Damage to the hippocampal formation, whether focal or diffuse, leads to severe impairment of short-term memory. The most common presenting symptom of Alzheimer disease is loss of short-term memory, and histologically the hippocampus is characteristically affected. Choline acetyltransferase, which is involved in the synthesis of acetylcholine, is depleted in the hippocampus in the disorder. Anticholinergic drugs administered to normal subjects can simulate some aspects of the memory defect seen in Alzheimer disease. It is postulated that damage to a cholinergic neuronal pathway running to or from the hippocampus underlies the memory disorder. This suggestion implies that it may be possible to improve memory in patients with Alzheimer disease by pharmacological means.