Aricept scientific update |
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Expert Opin Pharmacother. 2007 May;8(7):1011-23.
Seltzer B.
V.A. Boston Healthcare System, Department of Neurology, Harvard Medical School, Geriatric Research Center, Boston, MA 02130, USA.
Donepezil: an update.
An update on Donepezil Donepezil hydrochloride is the most widely prescribed drug for Alzheimer's disease (AD). The main mechanism of
action through which it influences cognition and function is presumed to be the inhibition of acetylcholinesterase
enzyme in the brain; however, donepezil may also impact the pathophysiology of AD at several other points.
Officially approved for mild-to-moderate and severe AD, donepezil has also been shown to be effective in
early-stage AD, vascular dementia, Parkinson's disease dementia/Lewy body disease and cognitive symptoms associated
with multiple sclerosis. In addition, one study suggested that donepezil may delay the onset of AD in subjects with
mild cognitive impairment, a prodrome to AD. The pharmacokinetics, pharmacodynamics, safety/tolerability profile
and drug interaction properties of donepezil make it an easy and safe agent to use. However, in general, the
efficacy of donepezil is limited, and ongoing studies are investigating other agents that may ultimately overtake
its present position as the mainstay of anti-AD therapy.
Epilepsia. 2007 May 1;
Hamberger MJ, Palmese CA, Scarmeas N, Weintraub D, Choi H, Hirsch LJ.
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
A Randomized, Double-Blind, Placebo-Controlled Trial of Donepezil to Improve Memory in Epilepsy.
How to improve Memory in Epilepsy: A Randomized, Double-Blind, Placebo-Controlled Trial using Donepezil. Purpose: To determine whether an acetylcholinesterase inhibitor, such as donepezil, would improve memory or other
cognitive/psychological functions in epilepsy patients with subjective memory complaints. Methods: Twenty-three
epilepsy patients with subjective memory difficulty were randomized to either 3 months of donepezil (10 mg/day) or
3 months of placebo treatment, and then crossed over to the other treatment arm. Patients and physicians were
blinded to treatment phase throughout data acquisition. Assessment of memory and other cognitive functions,
subjective memory, mood, and self-rated quality of life (QOL) and social functioning was performed at baseline and
following completion of both treatment phases. Seizure frequency and severity as well as treatment emergent adverse
effects were also monitored. Results: Donepezil treatment was not associated with improvement in memory or other
cognitive functions, mood, social functioning or QOL. Comparable increases in self-rated memory functioning
relative to baseline were evident during donepezil and placebo phases. Donepezil treatment was not associated with
increased seizure frequency or severity. Similar to group results, analysis of change within individual patients as
a function of treatment phase also showed neither significant benefit nor detriment associated with donepezil.
Conclusion: This study found no benefit on memory or other cognitive/psychological functions in a heterogeneous
group of epilepsy patients with subjective memory difficulty. Further investigation would be required to determine
whether individual patients, or those with particular epilepsy syndromes, might benefit from donepezil or other
acetylcholinesterase inhibitors, or if a higher dosage might be effective.
Dement Geriatr Cogn Disord. 2007 May 10;24(1):28-35
Saumier D, Murtha S, Bergman H, Phillips N, Whitehead V, Chertkow H.
Bloomfield Centre for Research in Aging and Lady Davis Institute, McGill University, Montreal, Que., Canada.
Cognitive Predictors of Donepezil Therapy Response in Alzheimer Disease.
Alzheimer Disease: Cognitive Predictors of Donepezil Therapy Response. Objectives: To examine whether the presence of domain-specific cognitive impairments would predict a response to
donepezil medication in patients with mild-to-moderate Alzheimer disease (AD). Methods: The protocol was an
open-label study of 30 AD subjects (mean age 74 years; education 11 years; Mini-Mental State Exam (MMSE) 23 of 30)
beginning a 6-month course of treatment with donepezil. Global response to treatment was determined using a
combination algorithm based on changes over 6 months in the ADAS-cog, MMSE and CIBIC. In addition, a set of
neuropsychological and experimental cognitive tests designed to test five domains of cognition were administered
before beginning therapy in order to determine which domain of testing would be predictive to response to
treatment. The tests examined attention, short-term and working memory, learning and memory, visuo-spatial motor
skills, and lexical-semantic knowledge. Results: Eighteen of the thirty subjects were rated as having responded
(stable or improved scores on the combination algorithm) to the therapy. Responders were significantly less
impaired prior to treatment on the following tests: the Clock Drawing Test, a Visual-Spatial Motor Tracking Test,
and the Boston Picture Naming Test. No significant initial group differences were noted on the other
neuropsychological or experimental cognitive measures. Conclusion: The tests that most reliably predicted response
to donepezil in AD subjects were in the domains of visual-spatial motor abilities and lexical-semantic functioning.
Int Psychogeriatr. 2006 Sep 28;:1-12
Matsuda O.
Department of Clinical Psychology, Faculty of Educational Psychology, Tokyo Gakugei University, Japan.
Cognitive stimulation therapy for Alzheimer's disease: the effect of cognitive stimulation therapy on the progression of mild Alzheimer's disease in patients treated with donepezil.
Alzheimer's disease: Cognitive stimulation therapy and its outcome on the progression of mild Alzheimer's disease in patients treated with donepezil. Background: There is general consensus regarding the benefit of acetylcholinesterase inhibitors (e.g. donepezil) in Alzheimer's disease (AD). However, the combined effect of acetylcholinesterase and cognitive stimulation therapy (CST) is still controversial.Objective: This study examines their combined effect on the progression of cognitive decline in AD by comparing the cognitive performance of 17 AD patients treated with CST and donepezil (combined treatment group) and 13 AD patients treated with donepezil alone (control group).Methods: Patients in the combined treatment group received 5 mg of donepezil per day and about 20 one-hour CST sessions for one year, whereas the control group received only 5 mg of donepezil per day. The first eight sessions were carried out once a week, and subsequent sessions were generally once every two weeks. The patients were evaluated for changes in cognitive ability by administering the Mini-mental State Examination (MMSE) before the start of CST (baseline) and about one year later (follow-up).Results: A repeated-measure analysis of variance revealed a significant group x time interaction. The MMSE score decreased significantly in the control group, but did not change significantly in the combined treatment group. Three patients in the control group declined by four points on the MMSE, compared to none in the combined treatment group. Effect size (ES) in the control group was relatively large and negative, while the ES in the combined treatment group was close to zero.Conclusions: The results suggest the possibility that donepezil plus CST slowed the rate of cognitive decline more than the administration of donepezil alone.
Ann Pharmacother. 2005 Mar;39(3):563-6. Epub 2005 Feb 08.
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.
Dramatic improvement in down syndrome-associated cognitive impairment with donepezil.
Down syndrome: theatrical improvement and associated cognitive impairment with donepezil. 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.
J Neurol Neurosurg Psychiatry. 2005 Mar;76(3):315-9.
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.
Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease.
Effects of donepezil treatment in Alzheimer's disease and the degree of inhibition in cortical acetylcholinesterase activity. 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.
Aricept description...
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Drug category:Anti-Alzheimer's, Anti-Dementia Agents
 Aricept scientific update
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