Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET).

Muscarinic cholinergic M1 and M2 receptors in young and aged adult male volunteers were studied using [N-11C-methyl]-benztropine, a specific muscarinic cholinergic receptor ligand, and high resolution positron emission tomography (PET). A regionally specific pattern of decreased binding was observed in aged volunteers. Using two separate methods of data analysis, thalamic, hippocampal and cerebellar regions showed no decreases in the apparent specific binding of [N-11C-methyl]-benztropine while frontal, parietal, temporal and occipital cortices as well as the corpus striatum showed age related changes in binding that declined (in 82 yrs old subject) to about 50% of the value obtained from the youngest volunteer (19 yrs). These data suggest that regions high in muscarinic receptor density, the corpus striatum and the cortical mantle, show a greater rate of decline than those areas that have a relatively low number of muscarinic receptors. Furthermore, this study demonstrates the usefulness of PET and [N-11C-methyl]-benztropine for assessing age related regional changes in muscarinic cholinergic receptor binding in the living human brain.