J Neurol Neurosurg Psychiatry.
2005 Mar;76(3):315-9. Degree of inhibition of cortical acetylcholinesterase
activity and cognitive effects by donepezil treatment in Alzheimer's
disease.
Bohnen NI, Kaufer DI, Hendrickson R, Ivanco LS, Lopresti BJ, Koeppe
RA, Meltzer CC, Constantine G, Davis JG, Mathis CA, Dekosky ST,
Moore RY.
University of Pittsburgh, Liliane S Kaufmann Building, Suite 811,
3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
OBJECTIVES: To determine in vivo cortical acetylcholinesterase (AChE)
activity and cognitive effects in subjects with mild Alzheimer's
disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.
METHODS: Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate
([(11)C]PMP) AChE positron emission tomography (PET) assessments
before and after donepezil therapy. RESULTS: Analysis of the PET
data revealed mean (temporal, parietal, and frontal) cortical donepezil
induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001).
Enzyme inhibition was most robust in the anterior cingulate cortex
(24.2% (6.9%), t = -14.1; p<0.0001). Donepezil induced cortical
inhibition of AChE activity correlated with changes in the Stroop
Color Word interference scores (R(2) = 0.59, p<0.01), but not
with primary memory test scores. Analysis of the Stroop test data
indicated that subjects with AChE inhibition greater than the median
value (>22.2%) had improved scores on the Stroop Color Word Test
compared with subjects with less inhibition who had stable to worsening
scores (t = -2.7; p<0.05). CONCLUSIONS: Donepezil induced inhibition
of cortical AChE enzyme activity is modest in patients with mild
AD. The degree of cortical enzyme inhibition correlates with changes
in executive and attentional functions.
Ann Pharmacother. 2005 Mar;39(3):563-6.
Epub 2005 Feb 08. Dramatic improvement in down syndrome-associated
cognitive impairment with donepezil.
Kondoh T, Amamoto N, Doi T, Hamada H, Ogawa Y, Nakashima M, Sasaki
H, Aikawa K, Tanaka T, Aoki M, Harada J, Moriuchi H.
Department of Pediatrics, Nagasaki University Hospital, Nagasaki,
Japan.
OBJECTIVE: To report 2 cases of patients with Down syndrome and
severe cognitive impairment who gained dramatic improvements in
quality of life (QOL) upon donepezil treatment. CASE SUMMARIES:
Case 1. A 38-year-old woman with Down syndrome, diagnosed with
secondary progressive dementia when her mental state had deteriorated
rapidly after graduation from junior high school, started donepezil
treatment. The loading dose was 3 mg/day and was increased to
5 mg/day for maintenance. One month after the dose was increased,
adverse effects such as soft stool and urinary incontinence appeared.
These adverse effects disappeared when the dose was decreased
again to 3 mg/day. Her QOL improved dramatically with this minimal
dose. She recovered verbal and written communication skills that
she had lost for the past 21 years. Case 2. A 22-year-old man
with Down syndrome, who had been diagnosed as having severe mental
retardation, was put on donepezil therapy. Both loading and maintenance
doses were 3 mg/day. His QOL had also dramatically improved, with
some recovery in verbal communication. Transient agitation/violence
and transient muscle weakness appeared during the first few months
of treatment. DISCUSSION: Patients with Down syndrome may be more
sensitive to donepezil therapy than others and may benefit from
this medicine, although they may also have adverse effects more
frequently. CONCLUSIONS: Donepezil may be a useful medicine for
some patients with Down syndrome with severe cognitive impairment
or mental retardation if the adverse effects are manageable.
