Differential cholinergic regulation in Alzheimer's patients compared to controls following chronic blockade with...

The effects of low-dose chronic scopolamine on measures of cerebral perfusion and muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and eight elderly controls. Single photon emission computed tomography (SPECT) scans using technetium-labelled hexamethypropylene amine oxide (99mTc-HMPAO) to measure cerebral perfusion before and after chronic scopolamine revealed a significant 12% increase in the normal controls (P < 0.01) while the AD subjects showed no significant change. In contrast, the controls showed decreased muscarinic binding as evidenced by 123I-quinuclidinyl-4-iodobenzilate (123I-QNB) labelling after chronic drug (-10%, P < 0.01) whereas the AD subjects showed increased 123I-QNB labelling (+8%, P < 0.05). The difference between 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 differences in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade.