Investigational treatment for vascular cognitive impairment

Cognitive impairment of any severity associated with cerebrovascular damage is defined as vascular cognitive impairment as proposed by O'Brien. This is a heterogeneous syndrome with many subtypes, the most prevalent being vascular cognitive impairment without dementia. Neuropathological studies confirm that cerebrovascular disease and Alzheimer's disease frequently coexist. Diagnosis depends on criteria for dementia and vascular pathologies. Brain imaging is an important diagnostic tool. Although there is no approved intervention specifically for vascular cognitive impairment, general treatments (such as antiplatelet and antihypertensives) aimed at the prevention and management of stroke are used. Evidence from randomised, placebo-controlled studies of cholinesterase inhibitors for vascular dementia suggests that there may be beneficial effects for cognitive function, and clinical global impression is more favourable for the cholinesterase inhibitors compared with placebo. The effect of memantine also seems to be modest and similar to the effect that is demonstrated in patients with Alzheimer's disease. The accumulated evidence is not as comprehensive as that which exists for Alzheimer's disease. The cholinesterase inhibitors and memantine have not been extensively studied in vascular cognitive impairment without dementia. For the purposes of this review, the authors focus on interventions that have been evaluated by randomised controlled trials.     

非痴呆性血管性认知功能障碍患者记忆功能研究

目的探讨非痴呆性血管性认知功能障碍（VCIND）患者记忆功能特点。方法选取VCIND患者21例（VCIMD组）、脑血管病无认知障碍（CVD）患者15例（CVD组）、对照组22例。入选对象均测查记忆力、注意力、语言能力,且采用改良的诊断标准进行诊断。结果VCIND组患者85．7％（18／21）有记忆功能减退的主诉,明显多于CVD组[26．4％（4／15）]和对照组[36．4％（8／22）]（P〈0．05）。简易智力状态检查：对照组（28．0±1．3）分,CVD组（28．5±lO）分,VCIND组（26。4±1．8）分;阿尔茨海默病评价量表一认知分表：对照组（5．1±2．6）分,CVD组（5．7±2．2）分,VCIND组（11．5±4．4）分;语言流畅性测验：对照组（16．0±2．6）分,CVD组（17．3±1．2）分,VCIND组（12．8±3．0）分。单词回忆：对照组（3．0±1．2）分,CVD组（3．1±1．2）分,VCIND组（5．3±2．0）分。VCIND组总体认知功能、记忆功能、语言功能较CVD组和对照组均明显衰退（均P〈0．05）。结论绝大多数VCIND患者存在近记忆力损害,词语记忆困难突出,且大多数以记忆力下降为首发症状。     

The status of ongoing trials for mild cognitive impairment

Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer’s disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.     

Prospects for prevention and treatment of vascular cognitive impairment

With the aging population and rising prevalence of vascular disease in developed and developing countries, increasing numbers of individuals are at risk of cognitive impairment. Despite the potential of the therapeutics that are currently under investigation, none have yet fulfilled their promise for the prevention and treatment of dementia. The term vascular cognitive impairment (VCI) describes individuals with significant cognitive impairment arising from vascular disease. Risk factors predisposing to stroke correlate with brain changes, cognitive loss and Alzheimer's disease pathology. The volume of the infarcts and white matter changes, silent lacunar infarcts, and global and regional brain atrophy may be imaged non-invasively, targeted as surrogates of the dementia processes and considered parameters to be targeted for interventional strategies. As the greatest chance to prevent cognitive impairment and its progression is by intervening in the early stages or prior to any change, the development of preventative therapeutics is an important strategy. Non-invasive magnetic resonance imaging techniques may help to identify a subgroup of patients in whom infarct prevention, via risk factor control, may be of paramount importance. As the pathophysiology of dementia becomes more fully understood by coupling neuropsychological with neuroimaging, genetic and pathological features, there is the potential for the establishment of diagnostic criteria of the early phase of VCI and the testing of novel interventional strategies.     

The status of ongoing trials for mild cognitive impairment

Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer's disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.     

血管性认知障碍的关键蛋白研究进展

血管性认知障碍是指由各种脑血管疾病引起的认知损害,范围包括从轻度认知损害到血管性痴呆。它通常会影响大脑的高级功能,特别是在执行功能和记忆方面。近年来随着血管性认知障碍发病率的逐步上升,针对血管性认知障碍发病机制的通路研究也在不断深入。本文对血管性认知障碍的关键靶蛋白进行综述,为血管性认知障碍的治疗和用药提供参考。     

Neuropsychological assessment of cognitive function in chronic alcohol-dependent patients and patients with Alzheimer's disease

BACKGROUND: Heavy and chronic alcohol dependence and Alzheimer's disease may share some neuropsychological characteristics. PATIENTS AND METHODS: The pattern of neuropsychological characteristics of 33 alcohol-dependent patients who reported memory disturbances were evaluated and compared to the neuropsychological performance of 38 patients with mild-stage Alzheimer's disease and 73 healthy subjects, serving as controls. Alcohol-dependent patients were examined with tools concerning the pattern of alcohol abuse and problems related to alcohol consumption. All groups completed a full battery of neuropsychological tests for the assessment of cognitive functions, such as different kinds of memory, attention, executive function etc. RESULTS: Alcohol-dependent patients fared worse compared to the control subjects in every test used. The comparison of alcohol-dependent patients versus patients with Alzheimer's disease showed that the latter are much more burdened, as far as cognition is concerned, in all aspects of memory. CONCLUSION: Alcohol-dependent patients, even if they are not demented, have mild cognitive impairment in all domains of cognition (memory and frontal functions) in comparison with controls which performed within the norms. Verbal fluency, working memory and frontal functions were impaired at the same degree in alcohol-dependent patients and in patients with Alzheimer's disease. Memory problems were more pronounced in Alzheimer's disease patients.     

The relative contributions of ecstasy and cannabis to cognitive impairment

RATIONALE: (+/-)-3,4-methylenedioxymethamphet-amine (MDMA; 'ecstasy'), a commonly used recreational drug, has typically been found to be related to poor cognitive function in humans. However, cannabis consumption may not have been adequately controlled for in these studies. OBJECTIVE: The present study was designed to further elucidate the relation between MDMA and cannabis in cognitive impairment. METHODS: Subjects who had used neither MDMA nor cannabis (controls; n=31), cannabis but not MDMA (cannabis users; n=18) and both MDMA and cannabis (MDMA/cannabis users; n=11) were compared on a battery of neuropsychological tests. RESULTS: The cannabis and MDMA/cannabis groups did not differ on any of the tests, whereas the combined cannabis and MDMA/cannabis groups performed more poorly than controls on tests of memory, learning, word fluency, speed of processing and manual dexterity. Further, apart from speed of processing where higher MDMA consumption predicted slower processing, covariate analysis revealed that the deficits were more closely related to cannabis than MDMA usage. CONCLUSION: The results suggest that cannabis is an important confound in studies of MDMA-related cognitive impairment, and that previously reported cognitive impairment in MDMA users may have been caused by coincident cannabis use.     

血管性认知功能障碍治疗研究进展

血管性认知功能障碍（VCI）是认知功能障碍的一个重要类型,由脑血管疾病的危险因素和／或血管性脑损害所导致的,从轻度认知功能障碍到痴呆的一大类综合征,是目前唯一可预防的痴呆类型。该文就 VCI 的药物和非药物治疗的现状及其进展作一综述。     

Alzheimer's disease and age-related memory decline (preclinical)

An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.     

卒中后认知功能损害的演变及治疗进展

脑卒中是我国中老人群最主要的死亡原因之一.卒中可导致神经功能缺损、行为、情感障碍外,认知功能损害很常见.认知功能损害是卒中复发的重要危险因子,使血管性痴呆发生的风险增高并影响病人的康复.研究卒中后认知功能损害的特征,以及病程中的演变轨迹及其相关影响因素,给予针对性干预及治疗,以减少及延缓认知损害的发生.该文对卒中后认知功能损害的演变及治疗进展进行综述.     

血管性认知功能障碍及其早期识别与干预的研究进展

血管性认知功能障碍（vascular cognitive impairment, VCI）是指由脑血管病及其危险因素引起的以不同程度认知功能损害为特点的一组临床综合征。在发展至血管性痴呆之前,早期诊断、早期干预可以预防和延缓VCI的发展,甚至逆转患者的认知功能损害。本文就VCI的概念、发病机制、生物学标志物及其预防和治疗等方面的研究进展作一综述。     

短暂性脑缺血发作后早期认知功能损害的研究进展

短暂性脑缺血发作可引起24h内可逆性的神经局灶损害,还可导致认知功能的损害,并可以延续到24h以后,反复的脑缺血发作可能对认知功能产生累积性的损害。近年来人们开始关注短暂性脑缺血所引起的认知损害问题,本文综述这一方面的研究进展。     

丁苯肽联合尼莫地平治疗血管性认知功能障碍疗效观察

目的 探讨丁苯肽联合尼莫地平治疗血管性认知功能障碍的临床效果.方法 160例血管性认知障碍患者,根据治疗方法分为对照组和观察组各80例,对照组单纯应用尼莫地平治疗,观察组丁苯肽联合尼莫地平治疗,分析比较两组治疗效果,并评估认知功能.结果 观察组显效率为58.75％ （47/80）,高于对照组的45.00％（36/80）（P=0.03）;观察组治疗后MoCA评分为（24.83 ±9.48）分,高于对照组的（21.64±9.52）分（P=0.04）.观察组治疗后ADL评分（58.31±11.27）分,高于对照组的（53.28±10.32）分（P=0.04）;观察组治疗后定向力、视空间与执行功能、延迟回忆和注意力,均高于对照组治疗后（P=0.03,0.02,0.04,0.02）.结论 丁苯肽联合尼莫地平治疗血管性认知功能障碍临床效果较好.     

轻度认知功能障碍与阿尔茨海默病患者血管危险因素的研究

目的 探讨血管危险因素与轻度认知功能障碍（Mild cognitive impairment,MCI）及阿尔茨海默病（Alzheimer＇sdisease,AD）的关系,并进一步分析各因素与认知功能下降程度的相关性.方法 选择2012年6月至2014年6月于门诊及住院部诊断为MCI及AD的患者各35例,同期体检的性别、年龄、文化程度相匹配的健康老人35例为对照.所有研究对象均进行MMSE、ADAS-Cog量表评定,采集晨空腹血进行血脂、血糖检测,并分别记录性别、年龄、身高、体重、吸烟、饮酒等情况.采用最小显著性差异法（LSD）比较各组间血管危险因素的差异、Pearson＇s相关分析各因素与认知功能评分的相关性.结果 与对照组相比,MCI组、AD组体重指数、血胆固醇水平呈进行性下降,但仅AD组与对照组相比差异有统计学意义.收缩压水平MCI组、AD组与对照组相比均明显升高,MCI组与AD组比较差异亦有统计学意义.Pearson＇s分析可见各因素与认知功能下降程度之间呈线性相关.糖尿病、饮酒比率AD组与对照组相比亦明显升高.结论 血管危险因素在老年人认知功能下降过程中有重要的作用,并有可能指导AD早期诊断及治疗.     

Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants

Ginkgo biloba extract (EGb) from the world's oldest living tree has been reputed to ameliorate cognitive decline in the elderly and slow cognitive deterioration in patients with dementia of the Alzheimer's type. EGb remains as one of the most popular plant extracts to alleviate symptoms associated with a range of cognitive disorders such as Alzheimer's disease, vascular dementia and age-related amnesic conditions. EGb is known to contain a range of chemically active components that have antagonistic effects on platelet-activating factor, free-radical scavenging activity and direct effects on the cholinergic neurotransmitter system. Recently there has been much speculation, that EGb may act as a 'smart drug' or nootropic agent in the healthy young to improve intelligence. We conducted a 30-d randomized, double-blind, placebo-controlled clinical trial in which 61 participants were administered a battery of validated neuropsychological tests before and after treatment. Statistical analysis indicated significant improvements in speed of information processing working memory and executive processing attributable to the EGb.     

血管性认知功能损害的病理机制与预防

血管性认知损害（VCI）是一种异质性疾病,由脑血管病变或脑灌流受损引起,涵盖了从轻微认知损害到血管性痴呆（VaD）。本文综述VCI的病理机制及其预防研究进展。     

Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats.

In the present study, the effect of alpha lipoic acid, a potent free radical scavenger, was investigated against the intracerebroventricular streptozotocin model of cognitive impairment in rats, which is characterized by a progressive deterioration of memory, cerebral glucose and energy metabolism, and oxidative stress. Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (50, 100 and 200 mg/kg) orally for 21 days starting from day 1 of streptozotocin injection in separate groups. The learning and memory behavior was evaluated and the rats were sacrificed for estimation of oxidative stress. The intracerebroventricular streptozotocin rats treated with alpha lipoic acid (200 mg/kg, p.o.) showed significantly less cognitive impairment as compared to the vehicle treated rats. There was also an insignificant increase in oxidative stress in the alpha lipoic acid treated groups. The study demonstrated the effectiveness of alpha lipoic acid in preventing cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin and its potential in dementia associated with age and age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.     

Chronic treatment with tocotrienol, an isoform of vitamin E, prevents intracerebroventricular streptozotocin-induced cognitive impairment and oxidative-nitrosative stress in rats

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, which is associated with increased oxidative stress in the brain of rats. In the present study, we investigated the effect of both the isoforms of vitamin E, α-tocopherol and tocotrienol against ICV STZ-induced cognitive impairment and oxidative-nitrosative stress in rats. Adult male Wistar rats were injected with ICV STZ (3 mg/kg) bilaterally. The learning and memory behavior was assessed using Morris water maze and elevated plus maze. The rats were sacrificed on day 21 and parameters of oxidative stress, nitrite levels and acetylcholinesterase activity were measured in brain homogenate. α-Tocopherol as well as tocotrienol treated groups showed significantly less cognitive impairment in both the behavioral paradigms but the effect was more potent with tocotrienol. Both isoforms of vitamin E effectively attenuated the reduction in glutathione and catalase and reduced the malonaldehyde, nitrite as well as cholinesterase activity in the brains of ICV STZ rats in a dose dependent manner. The study demonstrates the effectiveness of vitamin E isoforms, of which tocotrienol being more potent in preventing the cognitive deficits caused by ICV STZ in rats and suggests its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.     

脑小血管病性认知障碍血液学标志物的研究进展

如今,血管性认知障碍（vessel cognitive impairment,VCI）已成为痴呆的第2大病因,其中脑小血管病（cerebral small vessel disease,CSVD）被公认为VCI最常见的病因。临床实践中,脑小血管病认知功能障碍（CSVCI）的诊断主要通过神经量表评估、神经影像学等检查,并排除其他疾病导致认知功能障碍后得出诊断。近年来,因血液学标志物检测技术愈加成熟。众多学者认为,血液学标志物检测是一种简便、实用的检测手段,为CSVCI的临床诊断提供重要的参考价值,以此早期对CSVCI进行干预。本文主要对近10年CSVCI血液学标志物的研究进展作一综述。