Experimental hypertension induced vascular dementia: pharmacological, biochemical and behavioral recuperation by angiotensin receptor blocker and acetylcholinesterase inhibitor

Involvement of vascular pathology has been suggested in hypertension as well as vascular dementia (VaD), which also have a very high degree of co-occurrence in ageing population. We have recently reported that experimental diabetes as well as hyperhomocystenemia induces VaD. In the present research work, for the first time we are reporting the genesis of VaD by deoxycorticosterone acetate (DOCA)-salt induced experimental hypertension. Furthermore, we have also investigated the beneficial effect of telmisartan, an angiotensin II type 1 receptor blocker (ARB) and donepezil, an acetylcholinesterase inhibitor (AChEI), on DOCA-salt hypertension induced VaD in rats. DOCA-salt hypertensive rats performed poorly on Morris water maze, reflecting impairment in their learning and memory. Furthermore, DOCA-salt treatment has shown a significant impairment of vascular endothelial function (DOCA attenuated acetylcholine induced endothelium dependent relaxation), with a significant reduction in serum nitrite/nitrate levels, along with increased aortic, serum and brain oxidative stress levels (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and brain acetylcholinesterase activity. Treatments of telmisartan as well as donepezil significantly attenuated DOCA-salt hypertension induced learning and memory deficits, endothelial dysfunction, and changes in various biochemical parameters. It may be concluded that DOCA-salt hypertension induces VaD in rats. ARBs and AChEIs may be considered as potential pharmacological agents for the management of hypertension induced VaD.     

盐酸多奈哌齐配合综合康复治疗对颅脑外伤后记忆障碍的疗效观察

目的 探讨盐酸多奈哌齐配合综合康复训练治疗颅脑外伤(TBI)后记忆障碍的疗效和安全性.方法 广东省工伤康复医院神经康复科自2008年5月至2010年10月收住院行康复治疗的TBI康复期患者76例,其中给予综合康复治疗38例(对照组),综合康复治疗的基础上加用盐酸多奈哌齐治疗38例(治疗组),疗程3个月,治疗前后采用韦氏记忆量表(WMS)评价疗效并观察不良反应的发生.结果 与治疗前相比,对照组治疗后长时记忆中顺数、短时记忆中图片回忆和再认、瞬时记忆(背数)、WMS量表总分升高,差异均有统计学意义(P＜0.05);与治疗前比较,治疗组治疗后长时记忆(顺数、倒数、积累)、短时记忆中图片回忆、再认、逻辑记忆、瞬时记忆(背数)、WMS量表总分均升高,差异均有统计学意义(P＜0.05);与对照组治疗后比较,治疗组治疗后长时记忆中积累、短时记忆中逻辑记忆、WMS量表总分升高,差异有统计学意义(P＜0.05).盐酸多奈哌齐治疗过程中未见明显不良反应.结论 盐酸多奈哌齐配合综合康复治疗对TBI后记忆障碍较单纯采用综合康复治疗疗效更好.     

美金刚联合多奈哌齐对阿尔茨海默病患者认知功能及神经递质的影响

目的 探讨美金刚联合多奈哌齐对阿尔茨海默病(AD)患者认知功能及神经递质的影响.方法 选取北京航天总医院收治的AD患者100例,随机分为试验组(n=50)、对照组(n=50),对照组予以多奈哌齐治疗,试验组在此基础上予以盐酸美金刚治疗,比较2组临床疗效、AD评定量表的认知分量表(ADAS-Cog)评分、神经精神科问卷(...     

Cerebral ischemia combined with beta-amyloid impairs spatial memory in the eight-arm radial maze task in rats

beta-Amyloid (Abeta), a major component of senile plaques in Alzheimer's disease, has been implicated in neuronal cell death, a characteristic feature of this condition. In our previous experiments using primary cultures of hippocampal neurons, Abeta treatment induced neuronal cell death, displaying morphological characteristics of apoptosis that was significantly enhanced by hypoxia. Based on these results, we developed a simple in vivo rat model of Alzheimer's disease using cerebral ischemia, instead of hypoxia, combined with continuous intracerebroventricular administration of Abeta. The combination of cerebral ischemia and Abeta administration, but not either treatment alone, significantly impaired spatial memory in an eight-arm radial maze. A microdialysis study showed that spontaneous release of acetylcholine (ACh) from the dorsal hippocampus had a tendency to decrease in response to Abeta treatment alone or the combination of ischemia and Abeta. High K(+)-evoked increase in ACh release had a tendency to be inhibited by either ischemia or Abeta treatment alone and was significantly inhibited by the combination of both. Moreover, combination of ischemia and Abeta induced apoptosis of pyramidal neurons in the CA1 region of the hippocampus. Donepezil, a drug currently in clinical use for Alzheimer's disease, improved the impairment of spatial memory induced by cerebral ischemia combined with Abeta. These findings suggest that ischemia is an important factor facilitating the symptoms of Alzheimer's disease, and this model may be useful for developing new drugs for the treatment of Alzheimer's disease.     

脑灵汤治疗糖尿病认知障碍的临床疗效观察

【目的】观察脑灵汤治疗2型糖尿病(T2DM)认知障碍的临床疗效,并探讨其可能的作用机制。【方法】将74例2型糖尿病认知障碍患者随机分成治疗组和对照组,每组各37例。2组患者均给予常规糖尿病治疗,在此基础上,对照组患者给予盐酸多奈哌齐口服治疗,治疗组患者在对照组基础上加用脑灵汤治疗,疗程为6个月。观察2组患者治疗前后简易精神状态检查量表(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分、糖化血红蛋白(HbAlc)、空腹血糖(FBG)、早餐后2 h血糖(2hPBG)、体质量指数(BMI)及血糖波动指标[血糖波动幅度最大值(LAGE)、餐后血糖波动值(PPGE)、平均血糖波动幅度(MAGE)、日间血糖平均绝对差(MODD)]的变化情况,并评价2组患者的临床疗效及安全性。【结果】(1)治疗6个月后,治疗组的总有效率为94.59%(35/37),对照组为70.27%(26/37),治疗组的疗效明显优于对照组,差异有统计学意义(P<0.01)。(2)治疗后,2组患者MMSE评分均较治疗前提高(P<0.01),且治疗组对MMSE评分的提高作用优于对照组(P<0.01)。(3)治疗后,2组患者MoCA各项评分及总分均较治疗前提高(P<0.01),且治疗组对MoCA中的注意力、语言、延迟回忆评分及总分的提高作用明显优于对照组(P<0.01)。(4)治疗后,2组患者BMI、HbAlc、FBG、2hPBG、LAGE、早餐PPGE、MAGE、MODD水平均较治疗前降低(P<0.05),且治疗组对HbAlc、LAGE、早餐PPGE、MAGE、MODD水平的降低作用优于对照组(P<0.05)。(5)治疗过程中,2组患者均未出现明显不适症状,且患者的血、尿、大便常规和肝肾功能、心电图等安全性指标均未见异常改变。【结论】脑灵汤联合盐酸多奈哌齐治疗2型糖尿病认知障碍患者疗效确切,既可改善患者的临床症状和认知功能,又可改善患者的血糖波动指标。     

Quantitative analysis of the effects of donepezil on regional cerebral blood flow in Alzheimer’s disease by using an automated program, 3DSRT

INTRODUCTION: Donepezil, an acetylcholinesterase inhibitor, has been reported to have an effect that improves cerebral blood flow (CBF) alongside its primary effect on memory function. The aim of this study was to investigate the effects of long-term, low-dose donepezil therapy on blood perfusion in Alzheimer's disease (AD) by using a fully automated regional CBF quantification program named 3DSRT. MATERIALS AND METHODS: Fifteen subjects with mild to moderate AD according to NINCDS/ADRDA criteria underwent 99mTc-ethylcysteinate dimer (ECD) brain perfusion single photon emission computed tomography (SPECT) twice with an interval of 55.1 +/- 11.0 weeks. The dose of donepezil was fixed at 5 mg/day following the induction period (3 mg/day) of 2 weeks. Clinical efficacy of donepezil was assessed by using the Mini-Mental State Examination (MMSE). The results of SPECT imaging under exactly identical conditions were analyzed by 3DSRT, which enables us to perform a very objective assessment. RESULTS: Despite a decrease of the MMSE score from 20.9 +/- 4.7 to 18.7 +/- 5.7, CBF was increased in almost all cerebral areas except the left temporal segment. The increase was statistically significant in the left callosomarginal, right central, and bilateral pericallosal and lenticular nucleus segments. CONCLUSION: Thus far, no direct cerebrovascular effects have been reported for donepezil. We hypothesize that these CBF-promoting effects of donepezil might be related to increased neuronal activity and enhanced connection of neurons.     

盐酸多奈哌齐联合重复经颅磁刺激治疗老年痴呆的效果及对患者认知功能的影响

目的 探讨盐酸多奈哌齐联合重复经颅磁刺激(rTMS)治疗老年痴呆的效果及对患者认知功能的影响.方法 选取2017年6月至2019年6月我院收治的老年痴呆患者86例,采用随机数字法分为观察组和对照组,每组43例,两组患者均给予常规治疗及盐酸多奈哌齐片治疗.在此基础上,观察组患者给予rTMS治疗,对照组患者给予rTMS伪治...     

醒脑益智汤联合盐酸多奈哌齐治疗老年性痴呆临床研究

目的:观察醒脑益智汤联合盐酸多奈哌齐治疗老年性痴呆的疗效。方法:将老年性痴呆患者83例,按随机数字表法分为观察组43例与对照组40例,2组入院后均临床给予相关常规治疗,在此基础上,对照组给予盐酸多奈哌齐治疗,观察组在对照组基础上加用醒脑益智汤治疗,连续治疗3个月后评估2组临床疗效、中医证候评分、认知功能、精神行为及生活自理能力。结果:观察组治疗后总有效率(95.35%)高于对照组(67.50%)(P<0.05);2组治疗前中医证候积分及简易智能状态检查(MMSE)、神经精神问卷(NPI)、功能独立性评定量表(FIM)评分相比无显著性差异(P>0.05);2组治疗后中医证候积分明显降低,观察组低于对照组(P<0.05);2组MMSE、FIM评分明显升高,观察组高于对照组(P<0.05),2组治疗后NPI评分明显降低,观察组低于对照组(P<0.05)。结论:醒脑益智汤联合盐酸多奈哌齐治疗老年性痴呆患者疗效确切,可有效缓解患者临床症状和精神行为症状,有助于恢复患者认知功能和生活自理能力。     

计算机辅助认知训练联合多奈哌齐治疗卒中后认知障碍

目的研究计算机辅助认知训练联合多奈哌齐治疗卒中后认知障碍的临床疗效。方法筛选脑卒中后轻中度血管性认知障碍的患者83例,随机分为2组。其中,对照组42例予脑卒中规范治疗并口服盐酸多奈哌齐5 mg,qd;观察组41例在上述治疗基础上应用计算机辅助认知训练,40 min/d,每周5 d。治疗前及6周后应用蒙特利尔认知测验(MoCA)评价总体认知功能;数字广度测验评估注意力及工作记忆;连线测验评估执行功能;动物流畅性测验评估语言功能;改良Barthel指数(MBI)评估患者日常生活活动能力。结果治疗6周后,观察组和对照组在MoCA评分、数字广度测验正背及倒背、连线测验B-连线测验A、言语流畅性测验、日常生活能力评分均明显改善,差异有统计学意义(P<0.01)。其中,观察组在MoCA、数字广度测验正背及倒背、言语流畅性测验、日常生活能力评分方面较对照组明显提高,差异有统计学意义(P<0.05)。结论计算机辅助认知训练联合多奈哌齐治疗卒中后认知障碍,能显著改善患者整体认知功能、注意力、工作记忆、言语能力、日常生活能力,提高患者的生活质量。     

大明汤联合多奈哌齐治疗轻中度老年性痴呆患者的临床疗效

目的:观察大明汤联合多奈哌齐对老年性痴呆患者(AD)生活能力和认知功能的影响。方法:选取2013年1月至2017年1月广州中医药大学第三附属医院收治的AD患者60例为研究对象,按随机数字表分为对照组和观察组,每组30例。对照组给予盐酸多奈哌齐治疗;观察组在对照组基础上给予大明汤治疗,每剂煎药200 m L,分早晚2次口服,每日1剂。3个月为1个疗程,共治疗2个疗程,比较2组患者治疗前、治疗3个月、治疗6个月的简易精神状态检查(MMSE)、日常生活自理能力量表(ADL)、痴呆程度量表(CDR)以及认知功能评定量表(ADAS-cog)评分,比较治疗前后2组患者的血清同型半胱氨酸(Hcy)、尿酸(UA)水平及临床疗效。结果:治疗3个月、治疗后6个月后; 2组患者MMSE显著升高,差异有统计学意义(P 0. 05),CDR、ADL、ADAS-cog显著降低,差异有统计学意义(P 0. 05);观察组治疗后6个月的MMSE明显高于对照组,差异有统计学意义(P 0. 05),CDR、ADL、ADAS-cog明显低于对照组,差异有统计学意义(P 0. 05);观察组Hcy、UA水平显著低于对照组,差异有统计学意义(P 0. 05);观察组总有效率为77. 14%,明显高于对照组的48. 57%,差异有统计学意义(χ2=6. 668,P 0. 05),观察组患者的生活能力、认知能力改善好于对照组。结论:大明汤联合多奈哌齐对治疗轻中度AD的疗效显著。