博士 / 高雄醫學大學 / 醫學研究所 / 99 / The prevalence and incidence of Alzheimer’s disease (AD) is
increasing with aging. Pathological hallmarks for AD are mainly senile plaque, neurofibrillary tangle, and neuronal loss eventually. Currently the treatment of AD is mainly focused on acetyl-cholinesterase inhibitors(AChE-I)However, not every AD patient will respond to the treatment of AChE-I. Therefore, we conducted a study to measure and analyze the plasma concentration of AChE-I: donepezil in relation to the clinically therapeutic response. We have found that higher plasma concentration of doenepzil did not provide better therapeutic response. AD patients with their higher initial sum of boxes for clinical dementia rating (CDR) were
not good respond to the treatment as well as the higher initial Mini-Mental Status Examination (MMSE) score. In general, 58-60% of our AD patients will respond to these treatments regardless of age,education, gender, and their apo-lipoprotein E genotypes (ApoE),although ApoE genotype is a putative genetic factor to AD. Beyond ApoE gene, given to Angiotensin converting enzyme (ACE) can degrade the beta-amyloid, ACE gene is a putative genetic factor to AD, but its 5 effect was varied with races. We have recruited 257 AD patients and 137 non-demented Taiwanese to examine the genetic association and the ACE plasma protein level in relation to the various ACE genotypes. Our study has shown ACE insertion homozygote was a protective factor to AD
(p=0.040, OR=0.584, 95%CI: 0.349-0.976), for its lower ACE plasma protein level (114.79±31.32 ng/mL, p=0.023) compared to other genotypes.
The early diagnosis of AD is related to the therapeutic response. In order to diagnose AD at its early stage, we have translated and validated the AD8 questionnaire developed by Washington University in St Louis. We have recruited 239 normal cognitive and AD subjects into analyses. Our results have shown that the cut-off values were both 2 in differentiating normal (CDR=0) from very mild dementia (CDR=0.5) with the sensitivity 95.9% and specificity 78.7% and in differentiating normal (CDR=0) from dementia (CDR≧0.5) with the sensitivity 97.6% and specificity 78.1%, respectively.
My study began at evaluating clinically therapeutic response of acetyl-cholinesterase inhibitors to AD, validating AD8 questionnaire to screen early AD in order to have better therpaetic response in AD patients 6 in their early stage, and examining the association of ACE gene and AD.
Current study results are not sufficient to answer the questions for the treatment of donepezil to AD, especially in the difference of plasm concnetration, if any, between single dose and multiple doses of donepezil in AD patients. We also have to clarify whether cytochrome P450 will effect the donepezil concentration, and the various cognitive
responses, if any, under current dosage of donepezil 5 mg and coming higher dosage, 10 mg or 23 mg in the future.
| Identifer | oai:union.ndltd.org:TW/099KMC05534026 |
| Date | January 2011 |
| Creators | Yuan-Han Yang, 楊淵韓 |
| Contributors | Jing-kuan Liu, 劉景寬 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 183 |
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