Cholinergic system function and cognition in mild cognitive impairment.
Evidence for cholinergic dysfunction in very early stages of neurodegeneration like mild cognitive impairment (MCI) is inconclusive. Previous positron emission tomography (PET) studies based on small samples investigated if it is related to memory impairment. We examined whether cortical acetylcholine esterase (AChE) activity is reduced at this stage and correlated with cognitive function. N-[(11)C]-methyl-4-piperidyl acetate ([11C]MP4A), a positron emission tomography tracer for measuring cerebral AChE activity in vivo, was applied in 21 controls and 17 MCI patients. Parametric images of AChE activity were analyzed using standard atlas regions. Principal components analysis (PCA) of regional values of AChE activity and correlation analysis with neuropsychological test results was performed. Cortical AChE activity showed a significant decline in MCI patients compared with controls which was most pronounced in temporal regions. They formed the main part of a principal component that was related significantly to verbal and nonverbal memory, language comprehension and executive function. Cholinergic dysfunction is an early hallmark even before onset of dementia at the clinical stage of MCI. Its impact especially on temporal neocortex is associated with impaired neuropsychological function.
Max Planck Institute for Neurological Research, Cologne, Germany.
Cathleen
C
Haense
Elke
E
Kalbe
Karl
K
Herholz
Christoph
C
Hohmann
Bernd
B
Neumaier
Roman
R
Krais
Wolf-Dieter
WD
Heiss
D000110:Acetylcholinesterase / Q000502:physiology; D000368:Aged; D000679:Amygdala / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D059329:Cholinergic Neurons / Q000473:pathology*; D003071:Cognition / Q000502:physiology; D060825:Cognitive Dysfunction / Q000201:enzymology / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging
D000110:Acetylcholinesterase