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Abstract:
Recent use of acetyl cholinesterase inhibitors in Alzheimer's
Disease provides a valid probe to investigate the neurochemical
nature of cognitive systems. We carried out an extensive battery of
neuropsycholog ical tests and reaction time-based cognitive tests
of attentional and lexical processing in AD, before and after
treatment with two such drugs, Donepezil (Aricept), and
Metrifonate. Donepezil treatment was unblinded ( n = 17) and
Metrifonate treatment was double blind (n=6). Evaluation prior to
therapy and after six months of therapy demonstrated clinical
improvement consisting of increased "attentiveness" in 5/6
Metrifonate and 10/17 Donepezil subjects. Neuropsychological
testing failed to reveal statistically significant improvement in
general measures (Folstein Mini-mental test), measures of short
term memory, or other standard neuropsychological tests. In
contrast, reaction time-based measures of focussed and divided
attention (Stroop task, and visual search of a target amongst
varying number of distractors) demonstrated a robust improvement in
the case of both medications. This suggests (compatable with
previous work on Tacrine) that cholinergic medications have their
effect on attentional systems rather than directly on memory. It
further suggests that the clinical report of increased
"attentiveness" may in fact be a correlate of increased attention
on reaction time based tests. Short term memory, in contrast,
appears resistant to manipulation by cholinergic agents.
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