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Objective: Brain acetylcholinesterase activity was determined in healthy controls and in patients with mild cognitive impairment and early Alzheimer's disease.
Methods: A specific acetylcholinesterase tracer, [methyl-[C.sup.11]] N-methyl-piperidyl-4-acetate ([[C.sup.11]]MP4A), and a three dimensional PET system with magnetic resonance caregistration were used for imaging.
Results: There was a significant difference in the acetylcholinesterase activity in the hippacampus between the groups (p = 0.03), the mean (SD) acetylcholinesterase activity ([k.sub.3] values, [min.sup.-1]) being 0.114 (0.036) in controls, 0.098 (0.023) in mild cognitive impairment, and 0.085 (0.022) in Alzheimer's disease. The mini-mental state examination score showed no significant relation with acetylcholinesterase activity in any brain area in the combined mild cognitive impairment/Alzheimer group.
Conclusions: Hippocampal acetylcholinesterase activity is only slightly reduced in mild cognitive impairment and early Alzheimer's disease and so the value of in viva acetylcholinesterase measurements in detecting the early Alzheimer process is limited.
Cholinergic deficiency is the most severe and consistent biochemical change in Alzheimer's disease. This is seen as reduced levels of acetylcholine, choline acetyltransferase, and acetylcholinesterase, (1 2) reported in both necropsy brain samples and in cerebrospinal fluid. Only recently has it been possible to measure the acetyicholinesterase activity directly in the brain in viva.
With positron emission tomography (PET), cortical acetylcholinesterase activity has been evaluated by piperidyl derivatives such as N- [[C.sup.11]]methylpiperidyl-4-propionate ([[C.sup.11]]MP4P or [[C.sup.11]]PMP) (3) and N-[[C.sup.11]]methylpiperidyl-4-acetate ([[C.sup.11]]MP4A). (4-7) In these studies, the cortical cholinergic activity in Alzheimer's disease has been reported to decline by 16-45% compared with healthy controls.
Mild cognitive impairment is a transitional stage between normal aging and early Alzheimer's disease. (8 9) Individuals with mild cognitive impairment have memory impairment by definition, but their general cognitive function is normal and activities of daily living are intact. Volumetric magnetic resonance imaging (MRI) has shown that the entorhinal cortex and hippocampal volumes are reduced in mild cognitive impairment, (10) and that there is loss of entorhinal cortex neurones. (11) In PET studies, reduction of glucose metabolism in the hippocampal formation has been seen without any significant neocortical change. (12) Imaging results therefore indicate that at a structural and metabolic level the first pathological changes develop in the entorhinal and hippocampal areas. However, little is known about the cholinergic system in mild cognitive impairment.
We were interested to determine whether changes in the cholinergic system in the temporal regions could be detected in the early phases of the Alzheimer process. We therefore undertook [[C.sup.11]]MP4A PET studies in healthy controls and in patients with mild …