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Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: A positron emission tomography study
Author(s) -
Shinotoh Hitoshi,
Namba Hiroki,
Fukushi Kiyoshi,
Nagatsuka ShinIchiro,
Tanaka Noriko,
Aotsuka Akiyo,
Ota Tsuneyoshi,
Tanada Shuji,
Irie Toshiaki
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200008)48:2<194::aid-ana9>3.0.co;2-x
Subject(s) - acetylcholinesterase , nucleus basalis , neocortex , positron emission tomography , cholinergic , medicine , psychology , alzheimer's disease , statistical parametric mapping , amygdala , neuroscience , cardiology , cholinergic neuron , magnetic resonance imaging , disease , chemistry , radiology , biochemistry , enzyme
We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age‐matched controls by positron emission tomography (PET) and using a carbon 11–labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k 3 values were calculated as an index of acetylcholinesterase activity in a three‐compartment analysis using the metabolite corrected arterial input function. Twenty‐eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k 3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k 3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k 3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the 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 State Examination scores, supporting the cholinergic hypothesis in AD. Ann Neurol 2000;48:194–200