التفاصيل البيبلوغرافية
| العنوان: |
Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment |
| المؤلفون: |
Sokolow, Sophie, Li, Xiaohui, Chen, Lucia, Taylor, Kent D, Rotter, Jerome I, Rissman, Robert A, Aisen, Paul S, Apostolova, Liana G |
| المساهمون: |
Arosio, Beatrice |
| المصدر: |
Journal of Alzheimer's Disease, vol Preprint, iss Preprint |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Brain Disorders, Dementia, Aging, Clinical Research, Genetics, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Neurosciences, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, 80 and over, Apolipoprotein E4, Butyrylcholinesterase, Cholinesterase Inhibitors, Cognitive Dysfunction, Disease Progression, Donepezil, Female, Gene Frequency, Genotype, Humans, Indans, Longitudinal Studies, Male, Mental Status Schedule |
| جغرافية الموضوع: |
1 - 9 |
| الوصف: |
BackgroundDonepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results.ObjectivesTo determine whether BChE-K genotype predicts response to donepezil in MCI.MethodsWe examined the association between BChE-K genotype and changes in cognitive function using the data collected during the ADCS vitamin E/donepezil clinical trial in MCI.ResultsWe found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial. We found faster MMSE decline and CDR-SB rise in BChE-K homozygous individuals treated with donepezil compared to the untreated. We observed similar interactions between BChE-K genotype and steeper changes in MMSE and CDR-SB scores in APOE4 carriers treated with donepezil compared to controls.ConclusionBChE-K polymorphisms are associated with deleterious changes in cognitive decline in MCI patients treated with donepezil for 3 years. This indicates that BChE-K genotyping should be performed to help identify subsets of subjects at risk for donepezil therapy, like those carrying APOE4. BChE-K and APOE4 carriers should not be prescribed off-label donepezil therapy for MCI management. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt7xj4s3v5; https://escholarship.org/uc/item/7xj4s3v5Test |
| الإتاحة: |
https://escholarship.org/uc/item/7xj4s3v5Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.FFC6DE59 |
| قاعدة البيانات: |
BASE |
