Trial reportJournal of neural transmission (Vienna, Austria : 1996)2006
Changes in the activity and protein levels of CSF acetylcholinesterases in relation to cognitive function of patients with mild Alzheimer's disease following chronic donepezil treatment.
Trial report in Journal of neural transmission (Vienna, Austria : 1996), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia.The Cochrane database of systematic reviews · 2021Pooled it
- First-in-man study to investigate safety, pharmacokinetics and exploratory pharmacodynamics of HTL0018318, a novel MBritish journal of clinical pharmacology · 2021Trial
- Peripheral vascular responses to acetylcholine as a predictive tool for response to cholinesterase inhibitors in Alzheimer's disease.BMC neurology · 2019Trial
- Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Trial
- Concentration of Donepezil in the Cerebrospinal Fluid of AD Patients: Evaluation of Dosage Sufficiency in Standard Treatment Strategy.Neurotoxicity research · 2017Trial
- Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.European journal of clinical pharmacology · 2015Trial
- Different cholinesterase inhibitor effects on CSF cholinesterases in Alzheimer patients.Current Alzheimer research · 2009Trial
- Changes in brain 11C-nicotine binding sites in patients with mild Alzheimer's disease following rivastigmine treatment as assessed by PET.Psychopharmacology · 2007Trial
- Longitudinal plasma proteomics: relation to incident Alzheimer's disease dementia and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Presence of key cholinergic enzymes in human spermatozoa and seminal fluid†.Biology of reproduction · 2024Article
- Drug Distribution in Brain and Cerebrospinal Fluids in Relation to ICPharmaceutical research · 2022Article
- The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-Molecules (Basel, Switzerland) · 2021Article
- Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer's Disease: Nexus of Cholinergic and Nerve Growth Factor Dysfunction.Current Alzheimer research · 2021Review
- Donepezil and Rivastigmine: Pharmacokinetic Profile and Brain-targeting After Intramuscular Administration in Rats.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Influence of a genetic variant of CHAT gene over the profile of plasma soluble ChAT in Alzheimer disease.Genetics and molecular biology · 2020Article
- Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.Frontiers in pharmacology · 2020Article
- Influence ofPharmacogenomics and personalized medicine · 2019Article
- CSF Cholinergic Index, a New Biomeasure of Treatment Effect in Patients With Alzheimer's Disease.Frontiers in molecular neuroscience · 2019Article
- Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System.Clinical pharmacokinetics · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo evaluate long-term changes in acetylcholinesterase (AChE) activity in CSF and blood following donepezil treatment in relation to the concentration of donepezil and cognition in AD patients.
methodsCSF or blood (or both) samples of a total of 104 patients with mild AD were used [MMSE score 23 +/- 0.4; age 75 +/- 1 years (mean +/- SEM); n=53 for CSF and n=51 for plasma/red blood cell (RBC) samples]. The patients were treated with 5 or 10 mg/day donepezil and clinically followed for 2 years. The CSF and RBC AChE activities were measured by the Ellman's direct colorimetric assay. Protein levels of two variants of AChE ("read-through" AChE-R and synaptic AChE-S) were determined by an ELISA-like method.
resultsThe plasma donepezil concentration was dose-dependent (between 30 and 60 ng/mL in the 5-mg and 10-mg group, respectively). The CSF donepezil concentration was 10 times lower than the plasma level and showed dose- and time-dependent kinetics. The RBC AChE inhibition was moderate (19-29%). CSF AChE-S inhibition was estimated to 30-40% in the 5-mg and 45-55% in the 10-mg group. Positive correlations were observed between the CSF AChE inhibition, an increased protein level of the AChE-R variant and MMSE examination. Patients with high AChE inhibition (>or=45%) showed a stabilized MMSE test result after up to two years, while a significant decline was observed in AD patients with lower AChE inhibition (<or=30%).
conclusionsAn increase in the protein level of the AChE-R variant corresponded to a high AChE inhibition in CSF and favored less cognitive deterioration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.