IN-VIVO QUANTIFICATION OF CEREBRAL MUSCARINIC RECEPTORS IN NORMAL HUMAN AGING USING POSITRON EMISSION TOMOGRAPHY AND [C-11] TROPANYL BENZILATE

Regional cerebral muscarinic cholinergic receptor binding was quantifi ed in normal young and elderly subjects employing the muscarinic antag onist radioligand [C-11]tropanyl benzilate (TRB). Binding was determin ed by kinetic analyses of positron emission tomographic (PET) determin ations of cerebral activity in conjunction with radial arterial blood sampling following intravenous radiotracer injection. A significant, b ut minor (8%), loss of frontal cortical receptors relative to whole br ain average receptor density was found with advancing age. Parametric estimates of binding suggest small reductions in cerebral cortex bindi ng as well as increases in brain stem and cerebellar binding underlyin g the observed pattern difference. However, these latter changes did n ot achieve statistical significance. We conclude that cerebral muscari nic receptor availability, as depicted by antagonist binding, does not undergo a major decline during normal aging of the adult human brain. The cerebral cortical cholinergic dysfunction in elderly subjects, su ggested by prior clinical evidence, is not attributable to major loss of total muscarinic cholinoceptive capacity.