Treatment of Alzheimer’s disease across the spectrum of severity

Alzheimer’s disease (AD) is the most common cause of dementia affecting nearly 18 million people around the world and 4.5 million in the US. It is a progressive neurodegenerative condition that is estimated to dramatically increase in prevalence as the elderly population continues to grow. As the cognitive and neuropsychiatric signs and symptoms of AD progresses in severity over time, affected individuals become increasingly dependent on others for assistance in performing all activities of daily living. The burden of caring for someone affected by the disorder is great and has substantial impact on a family’s emotional, social and financial well-being. In the US, the currently approved medications for the treatment of mild to moderate stages of AD are the cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest efficacy in terms of symptomatic improvement and stabilization for periods generally ranging from 6 to 12 months. There are additional data that have emerged, which suggest longer-term benefits. For the moderate to severe stages of AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in widespread use and has shown modest benefit as monotherapy and in combination with ChEIs. The cost effectiveness of the currently available therapeutic agents for AD has undergone great scrutiny and remains controversial, especially outside the US. Neuropsychiatric symptoms such as agitation and psychosis are common in AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)-approved agents for the treatment of these symptoms, although atypical antipsychotics have shown some efficacy and have been widely used. However, the use of these agents has recently warranted special caution due to reports of associated adverse effects such as weight gain, hyperlipidemia, glucose intolerance, cerebrovascular events, and an increased risk for death. Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.     

老年人颅脑外伤后缺血性脑卒中发作特点及治疗

目的探讨老年人颅脑外伤后缺血性脑卒中发作特点及个性化治疗方案。方法针对7例颅脑外伤后急性期出现缺血性脑血管病症状的老年患者，通过脑血管造影检查分析其发病原因并根据不同的脑血管特点决定治疗方案。结果大多数患者（6／7）受伤前已存在不同程度的颅内外血管狭窄、血管壁溃疡以及附壁血栓形成等改变，提示脑缺血发作主要与这些病变为基础的脑血流下降、血栓脱落等因素密切相关。而外伤后脑灌注降低、脑血管痉挛是脑缺血发作的诱发因素。结论老年人外伤后的缺血性脑卒中发作主要与原有的脑血管基础疾病有关，预防和治疗老年人外伤后缺血性脑卒中发作，应基于这些病变特征并选择个体化治疗方案。     

A national stroke quality register: 12 years experience from a participating hospital

Registration of all hospitalized stroke patients is practiced in Sweden in order to assess care quality. Data in this register, Riks-Stroke (RS), may be biased due to incomplete registration. The purpose of this paper was to report changes in stroke outcome in relation to fluctuations in registration. Patients registered in RS at a hospital during the period 1994–2005 were analyzed. Case fatality at 28 days, living conditions, and activities of daily living (ADL) performance at 3 months were correlated to the number of patients registered and follow-up frequency. A total of 4994 stroke cases were registered during the period. A high annual registration rate was significantly correlated to a high case fatality ratio. A low annual follow-up rate was associated with a low proportion of patients living in their own home without any need of help. Quality parameters are sensible for selection bias, which make them difficult to compare over time and between hospitals. We suggest that by weighing outcome data against stroke severity, safer conclusions may be drawn. Additionally, hospitals considering setting up quality registers should make every effort to attain complete case ascertainment at all times, including patients managed outside the hospital, in order to avoid selection bias.     

依达拉奉防治缺血性脑损伤研究的新进展

近年来,依达拉奉脑保护作用的研究取得了很大进展,尤以对缺血性脑卒中和新生儿缺血缺氧性脑病的防治研究最为深入,而联合治疗策略也得到了广泛的重视.本文就近5年这些热点研究的新进展进行综述.     

急性缺血性卒中大血管闭塞性质的判断与取栓方式和材料的选择

血管内机械取栓是治疗大血管闭塞性急性缺血性卒中的有效治疗方法。应结合病史、发
病形式及影像学检查等综合判断病变性质；依据病变性质并参考手术路径，个性化选择支架取栓、
抽吸取栓、球囊/支架血管成形术、动脉溶栓任一种或多种方法联合取栓；并依据手术方式选择手
术材料，以快速高效地完成手术。     

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. METHODS: Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.     

急性缺血性卒中患者发生院内消化道出血的危险因素分析

目的 分析急性缺血性卒中患者（acute ischemic stroke，AIS）住院期间消化道出血（gastrointestinal
bleeding，GIB）的发生率、发生时间及危险因素。
方法 本研究纳入首都医科大学附属北京天坛医院急性卒中院内并发症队列（inhospital medical
complication after acute stroke，iMCAS）研究中AIS患者。收集患者临床信息，根据住院期间是否发生
GIB分为GIB组和无GIB组，采用多因素Logistic回归模型，分析AIS患者发生GIB相关危险因素。
结果 共纳入1129例AIS患者，平均年龄58.7±12.5岁，女性230例（20.4%）。47例住院期间发生GIB，
发生率为4.2%，卒中发作至GIB确诊时间为5（3～13）d。合并肝硬化（OR 10.06，95%CI 2.44～41.38）、
高入院NIHSS评分（OR 1.13，95%CI 1.08～1.19）、高白细胞计数（OR 1.25，95%CI 1.13～1.38）、住院时
间长（OR 1.05，95%CI 1.01～1.10）是AIS患者发生消化道出血的独立危险因素。
结论 本单中心研究数据提示合并肝硬化、高入院NI HSS评分、高白细胞计数、住院时间长是AI S患
者住院期间发生GIB的独立危险因素。     

老年认知功能障碍与脑结构CT测量的相关性研究

目的探讨脑萎缩与老年认知功能障碍之间的相关性。方法对开滦集团公司1063名离退休职工进行健康查体,用简易精神状态量表(MMSE)评定认知功能,按分界值将本次研究对象分为认知功能障碍组和认知功能正常组,同时用CT线性测量脑的相关部位以诊断脑萎缩情况,并对各型脑萎缩与认知功能的相关系数及提示老年认知功能障碍的敏感度、特异度、准确度进行分析。结果1063名观察对象中符合入选标准并资料完整者共计511名,其中108名有认知功能障碍,髓质脑萎缩55名、皮质萎缩5名、混合型萎缩30名;认知功能正常者403名,髓质脑萎缩214名、皮质萎缩13名、混合型萎缩62名。认知功能障碍组脑萎缩的发病率高于认知功能正常组,差异具有统计学意义(P<0.005);2组间颞叶海马钩回间距(26.86mm±3.73mmvs25.95mm±3.80mm)及海马钩回间距/大脑左右径的比值(0.21±0.02vs0.20±0.02)差异具有统计学意义(P<0.05);海马钩回间距、皮质脑萎缩、混合型脑萎缩与认知功能障碍呈负相关(分别为r=-0.094,P=0.034,r=-0.156,P≈0.000,r=-0.147,P≈0.000),以海马钩回间距20mm提示老年认知功能障碍的敏感度最高(98.14%),混合型脑萎缩的特异度(84.86%)、准确度最高(72.80%)。结论CT测量相关脑结构,判断脑萎缩类型可以为老年认知功能障碍的诊断提供有价值的信息。