In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism.
Memory and attention are cognitive functions that depend heavily on the cholinergic system. Local activity of acetylcholine esterase (AChE) is an indicator of its integrity. Using a recently developed tracer for positron emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A), we measured regional AChE activity in 4 non-demented subjects, 4 patients with dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body type (SDLT), and compared the findings with measurements of blood flow (CBF) and glucose metabolism (CMRGlc). Initial tracer extraction was closely related to CBF. AChE activity was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas. AChE activity in SDLT was in the lower range of values in DAT. Our results indicate that, compared to non-demented controls, there is a global reduction of cortical AChE activity in dementia.


BACKGROUND
Dementia, cholinergic system, acetylcholine esterase, positron emission tomography, cerebral blood flow, cerebral glucose metabolism.
Herholz
K
K
Max-Planck Institut für neurologische Forschung und Neurologische Universitätsklinik, Koln, Federal Republic of Germany.
Bauer
B
B
Wienhard
K
K
Kracht
L
L
Mielke
R
R
Lenz
M O
MO
Strotmann
T
T
Heiss
W D
WD
D000085:Acetates / Q000493:pharmacokinetics; D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010880:Piperidines / Q000493:pharmacokinetics; D012016:Reference Values; D012044:Regression Analysis; D013788:Thalamus / Q000378:metabolism; D014055:Tomography, Emission-Computed
D000085:Acetates; D002250:Carbon Radioisotopes; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; D000110:Acetylcholinesterase; D005947:Glucose