DIFFERENTIAL CHOLINERGIC REGULATION IN ALZHEIMERS PATIENTS COMPARED TO CONTROLS FOLLOWING CHRONIC BLOCKADE WITH SCOPOLAMINE - A SPECT STUDY

The effects of low-dose chronic scopolamine on measures of cerebral pe rfusion and muscarinic receptors were tested in eight Alzheimer's dise ase (AD) subjects and eight elderly controls. Single photon emission c omputed tomography (SPECT) scans using technetium-labelled hexamethypr opylene amine oxide (Tc-99m-HMPAO) to measure cerebral perfusion befor e and after chronic scopolamine revealed a significant 12% increase in the normal controls (P < 0.01) while the AD subjects showed no signif icant change. In contrast, the controls showed decreased muscarinic bi nding as evidence by I-123-quinuclidinyl-4-iodobenzilate (I-123-QNB) l abelling after chronic drug (-10%, P < 0.01) whereas the AD subjects s howed increased I-123-QNB labelling (+ 8%, P < 0.05). The difference b etween AD and control subjects was even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing to a double dissociation in the SPECT results. These data cannot be explained by group differen ces in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade.