Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: A positron emission tomography study

We measured brain acetylcholinesterase activity in 30 patients with Alzheim er's disease (AD) and 14 age-matched controls by positron emission tomograp hy (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD pat ients had repeat PET scans. The k(3) values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the met abolite corrected arterial input function. Twenty-eight of the 30 AD patien ts (14 each in the early and late onset subgroups) were retained in the stu dy so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k(3) values were significan tly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k(3) values were significantly reduced only in th e temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of c ortical k(3) values in the second PET scans, with a mean interval of 2 year s, suggesting a progressive loss of the ascending cholinergic system from t he nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k(3) values and Mini-Mental St ate Examination scores, supporting the cholinergic hypothesis in AD.