RT Journal
A1 Davis KL, Mohs RC, Marin D, et al
T1 CHolinergic markers in elderly patients
with early signs of alzheimer disease
JF JAMA
JO JAMA
YR 1999
FD April 21
VO 281
IS 15
SP 1401
OP 1406
DO 10.1001/jama.281.15.1401
UL http://dx.doi.org/10.1001/jama.281.15.1401
AB Context 
                  A central tenet of Alzheimer disease (AD) is the loss
of cortical cholinergic function and cholinergic markers in postmortem
brain specimens. Whether these profound deficits in cholinergic markers
found in end-stage patients are also found in patients with much
earlier disease is not known.Objective 
                  To determine whether cholinergic deficits in AD precede,
follow, or occur in synchrony with the earliest signs of cognitive
deterioration.Design, Setting, and Patients 
                  Postmortem study of nursing
home residents with Clinical Dementia Rating (CDR) Scale scores of 0.0
to 2.0 and 4.0 to 5.0 who underwent autopsy between 1986 and 1997,
comparing the activity of the cholinergic marker enzymes in the
cortices of 66 elderly subjects with no (CDR score=0.0;
n=18), questionable (CDR score=0.5;
n=11), mild (CDR score=1.0;
n=22), or moderate (CDR score=2.0;
n=15) dementia vs subjects with severe dementia (CDR
score=4.0-5.0; n=15).Main Outcome Measures 
                  Activity of the cholinergic marker enzymes
choline acetyltransferase and acetylcholinesterase in 9 neocortical
brain regions.Results 
                  The activity of choline acetyltransferase and
acetylcholinesterase in 9 neocortical brain regions did not differ
significantly in subjects with CDR scores of 0.0 to 2.0, but was
significantly lower in subjects with severe dementia (CDR
score=4.0-5.0). Choline acetyltransferase levels were
significantly correlated with severity of neuropathological lesions of
AD, as measured by density of neuritic plaques and neurofibrillary
tangles.Conclusions 
                  Although neocortical cholinergic deficits are
characteristic of severely demented AD patients, in this study,
cholinergic deficits were not apparent in individuals with mild AD and
were not present until relatively late in the course of the disease.
These results suggest that patients with more severe disease should be
a target for cholinergic treatment.