Reduction of choline acetyltransferase activity in primary visual cortex in mild to moderate Alzheimer's disease.
BACKGROUND
Cholinergic deficits in the primary visual cortex (PVC) may underlie some of the abnormalities in visual processing and global cognitive performance in Alzheimer's disease (AD).


OBJECTIVE
To correlate measures of general cognition (Mini-Mental State Examination and Global Cognitive Score) and visuospatial function with choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities, and nerve growth factor protein levels in the PVC.


METHODS
The ChAT and AChE enzyme assays and a nerve growth factor protein enzyme-linked immunoabsorbent assay were performed on PVC tissue samples from subjects clinically diagnosed as having mild cognitive impairment (MCI), AD, or no cognitive impairment (NCI).


METHODS
Nuns, priests and brothers enrolled in the Religious Order Study, with annual premortem records of neuropsychological testing.


RESULTS
Significant differences in ChAT activity, but not in AChE activity or nerve growth factor protein levels, were found among diagnostic groups (P = .049). The ChAT activity was lower in AD than in MCI or NCI (P<.01); MCI was not different from NCI. The PVC ChAT activity correlated with measures of overall cognitive function (Mini-Mental State Examination and Global Cognitive Score), but less so with a composite measure of visuospatial function.


CONCLUSIONS
The reduction in ChAT activity in the PVC of mild to moderate AD, but not in MCI, might serve to distinguish between clinical and preclinical forms of the disease. It appears that this change relates to generalized cognitive abnormalities but not specifically to visuospatial function.
Ikonomovic
Milos D
MD
Department of Neurology and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA 25213, USA.
Mufson
Elliott J
EJ
Wuu
Joanne
J
Bennett
David A
DA
DeKosky
Steven T
ST
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000523:psychology; D000704:Analysis of Variance; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D018709:Statistics, Nonparametric; D014793:Visual Cortex / Q000201:enzymology* / Q000473:pathology
D002795:Choline O-Acetyltransferase