Vascular Cognitive Impairment

Abstract: The term vascular cognitive impairment (VCI) is now employed to capture the spectrum of illness and disability arising from impaired cognitive function of vascular origin. As such, it supplants the more narrowly focussed terms "Vascular dementia (VaD)" and "multi-infarct dementia". It is meant to include both those whose cognitive impairment is different from that assumed by the usual criteria for dementia. Traditionally, dementia criteria have been modelled on AD, a disorder with more characteristic neuropathological and clinical disease expression than is seen in VaD, which can occur in many forms. VCI is common, and is associated with many adverse outcomes, including worse cognition, institutionalization, and death.
One form of VCI is coincident AD and VaD, a category which, although it has been comparatively neglected, may be amongst the most common forms of dementia. Another common form of VCI has a predilection for subcortical ischemic lesions, and for a clinical presentation which reflects frontal and subcortical involvement.
At present, there is no specific treatment for VCI, although several agents appear to offer the hope of both treatment and prevention. Further research on the clinical, pathological and mechanistic underpinnings of this important syndrome is needed. For a long time, VaD has been recognized as the second most common cause of dementia.^1,2) More recently, however, the concept of cognitive impairment in relation to cerebrovascular disease has been expanded. This paper will review the notion of "vascular cognitive impairment" (VCI) as it relates to clinical practice, and to our understanding of disease mechanisms in dementia and related disorders. It will propose that while the expanded concept has merit, within it are to be found distinct subgroups, including some of particular importance as targets for clinical trials of therapeutic and even preventive interventions.     

Spectrum of disease in vascular cognitive impairment.

The recognition that cognitive impairment of vascular origin is not limited to multi-infarct dementia has led to the development of several sets of new criteria for vascular dementia (VaD). We set out to define the spectrum of disease in patients presenting with vascular cognitive impairment (VCI). Of 412 patients consecutively seen at a memory clinic, 80 had VCI. These patients had vascular cognitive impairment not dementia (n = 19), VaD (n = 48), and mixed Alzheimer's disease-VaD (n = 13). Radiographic patterns were: white matter changes only (40%); multiple infarcts (30%); single strategic stroke (14%), and no identified lesion (16%). Of note, 19 (24%) of these patients meet none of the currently published criteria for VaD. To better understand and treat ischaemic causes of cognitive impairment, the concept of VaD should be expanded to include patients who do not meet traditional dementia criteria.     

血管性痴呆和血管性认知障碍的临床研究进展

血管性认知障碍和痴呆是认知障碍和痴呆领域以及脑血管病领域研究方面的交叉点。本文综述了血管性痴呆和认知障碍的定义、诊断标准和药物治疗进展。在诊断方面重点介绍了血管性痴呆各个亚型的临床特点。在治疗方面重点介绍了血管性痴呆和认知障碍的胆碱能递质代谢障碍以及胆碱酯酶抑制剂治疗的进展。     

Diagnosis and management of vascular cognitive impairment and dementia

Vascular dementias (VaDs) are the second most common cause of dementia. Cerebrovascular disease (CVD) and stroke relates to high risk of cognitive impairment, but also relate to Alzheimer's disease (AD): Vascular cognitive impairment (VCI) and dementias extend beyond the traditional multi-infarct dementia. Pathophysiology of VaD incorporates interactions between vascular etiologies (CVD and vascular risk-factors), changes in the brain (infarcts, white matter lesions, atrophy), host factors (age, education) and cognition. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current criteria have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Should new criteria be developed? Ideally in constructing new criteria the diagnostic elements should be tested with prospective studies with clinical-pathological correlation: replace dogma with data. Meanwhile focus on more homogenous subtypes of VaD, and on imaging criteria could be a solution. Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischaemic white matter lesions as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities "Binswanger's disease" and "the lacunar state". AD with VaD (mixed dementia) has been underestimated as a prevalent cause in the older population. In addition to simple co-existence, VaD and AD have closer interaction: several vascular risk factors and vascular brain changes relate to clinical manifestation of AD, and they share also common pathogenetic mechanisms. Vascular cognitive impairment (VCI) is a category aiming to replace the "Alzhemerized" dementia concept in the setting of CVD, and substitute it with a spectrum that includes subtle cognitive deficits of vascular origin, post-stroke dementia, and the complex group of the vascular dementias. As far there is no standard treatment for VaDs, and still little is known on the primary prevention (brain at risk for CVD) and secondary prevention (CVD brain at risk for VCI/VaD). There is no standard symptomatic treatment for VaD. Recently symptomatic cholinergic treatment has shown promise in AD with VaD, as well as probable VaD. Future focus should be directed to the distinct etiological and pathological factors: the vascular and the AD burden of the brain.     

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions.Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.     

Inter-rater reliability of the diagnosis of vascular cognitive impairment at a memory clinic

Consensus criteria for the diagnosis of vascular dementia (VaD) are gradually being replaced with data-based criteria. We report the inter-rater reliability of a new set of empirically-derived criteria for vascular cognitive impairment (VCI). Stratified sampling, with optimal allocation, was employed to randomly select 36 patients from the Queen Elizabeth II Health Science Centre's Memory Disability Clinic. Chart reviews were conducted independently by 4 physicians. Each physician classified the patients as having either: no cognitive impairment, VCI or Alzheimer's disease (AD). VCI was further classified both clinically (VCI without dementia, VaD or AD with a vascular component) and radiographically (infarcts, white matter changes, single strategic stroke). The intraclass correlation coefficient (ICC) for the diagnosis by physicians of VCI or otherwise was based on a repeated-measures analysis of variance with raters as the independent variable. A significant coefficient of reliability (average ICC = 0.88, 95% CI = 0.80-0.93) was obtained (H(o): rho 相似文献   

Vascular aspects of cognitive impairment and dementia

Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer''s disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors—hypertension and stroke—could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin–angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD.     

Treatment of vascular dementia--evidence from clinical trials with cholinesterase inhibitors

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. In addition, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment (VCI) and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitor agents used in AD. Controlled clinical trials with donepezil, galantamine and rivastigmine in VaD, as well as in patients with AD plus CVD, have demonstrated improvements in cognition, behavior and activities of daily living.     

Vascular cognitive impairment: current concepts and clinical developments

Vascular cognitive impairment (VCI) comprises a range of cognitive disorders related to cerebral vessel disease and has generally replaced the term multi-infarct dementia. Despite the heterogeneity of the VCI construct, some clinical patterns can be discerned, which enable subtypes, such as mixed dementia and VCI-no dementia, to be recognised. Diagnostic criteria for vascular dementia do not encompass the full range of the VCI construct, and clinical investigators now recognise the need for harmonised standards to study the many manifestations of VCI seen in daily practice and to inform the development of diagnostic criteria. Although executive dysfunction is a recognised feature of VCI, some data suggest a less exclusive role than was previously proposed. VCI might be preventable, although the evidence for this is not as complete as it is for the prevention of stroke. Future studies into specific therapies for VCI will need to consider the clinical features and outcomes carefully.     

MRI and CT in the diagnosis of vascular dementia

Neuroimaging is necessary to demonstrate cerebrovascular disease (CVD) and is therefore an important examination in vascular dementia (VaD) and vascular cognitive impairment (VCI). MRI is preferred over CT because multiple planes and sequences are needed to assess various types of pathology in relevant regions. These protocols allow differentiation of VaD from other forms of dementia and sometimes identify specific underlying disorders. Different diagnostic criteria for VaD exist but the NINDS-AIREN criteria are widely used in controlled clinical trials in VaD. These criteria have relatively low sensitivity but are highly specific and include radiological requirements. The radiological criteria have poor interobserver agreement. In general, the radiological portion of the diagnostic criteria for VaD needs revision and refinement to include bone fide cases of VaD not currently accepted by imaging rules, and for the early detection of patients with VCI.     

尼莫地平联合阿托伐他汀治疗血管性认知障碍的疗效观察

目的探讨尼莫地平联合阿托伐他汀治疗血管性认知障碍的临床疗效及其不良反应。方法将96例血管性认知障碍患者随机分为对照组和治疗组,每组48例,再根据神经心理学评分将每组分为VCIND和VaD两个亚组。对照组给予了常规治疗＋安慰剂治疗,治疗组予尼莫地平＋阿托伐他汀治疗,尼莫地平30mg/d,1日3次,阿托伐他汀20mg/d,晚上1次,疗程均为6个月。采用MoCA和ADL评分对患者进行神经心理学评分。结果与同组治疗前相比,治疗组治疗6个月后MoCA和ADL评分分值明显提高（P〈0.01）;与对照组相比,治疗组治疗后MoCA和ADL评分值提高（P〈0.05）。对照组中VCIND患者MoCA和ADL较治疗前降低（P〈0.05）;治疗组中VCIND患者较治疗前及对照组MoCA和ADL分值明显提高（P〈0.01）,VaD患者无明显提高（P〉0.05）。2组均未见严重的不良反应。结论尼莫地平联合阿托伐他汀治疗血管性认知障碍的临床疗效较好,不良反应少。     

Towards defining the neuropathological substrates of vascular dementia

Cerebrovascular disease is highly heterogeneous but can culminate in vascular cognitive impairment or vascular dementia (VaD). As much as the clinical diagnosis warrants scrutiny, the neuropathological substrates of VaD also need to be better defined. Atherosclerosis and small vessel disease are the main causes of brain infarction. Lacunar infarcts or multiple microinfarcts in the basal ganglia, thalamus, brainstem and white matter are associated with more than half of VaD cases consistent with subcortical ischaemic VaD. White matter changes including regions of incomplete infarction are usually widespread in VaD, but their contribution to impairment is not explicit. Other pathologies including hippocampal injury and Alzheimer type of lesions may also modify the course of dementia. Similar to other common dementias consensus criteria for VaD need unambiguous definition to impact on preventative and treatment strategies and are critical for selective recruitment to clinical trials.     

Physical activity in vascular cognitive impairment: Systematic review with meta-analysis

BackgroundVascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI.MethodsA systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up.ResultsThere was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I² 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD.ConclusionsThese findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.     

急性缺血性卒中患者血管性认知障碍及其亚型的相关因素分析

目的探讨急性缺血性卒中患者血管性认知障碍(vascular cognitive impairment,VCI)及其亚型非痴呆性血管性认知障碍(VCI-no dementia,VCIND)与血管性痴呆(vascular dementia,Va D)发生的主要相关因素。方法选择2014年6月至2015年6月就诊于天津医科大学总医院神经内科的491例急性缺血性卒中患者为研究对象,应用前期已建立的血管性认知障碍数据库记录患者的一般人口学信息、病史、体格检查、血管危险因素、生化及影像检查信息,对患者进行美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分、Essen评分及低分子肝素治疗急性卒中试验(the Trial of Org 10172 in Acute Stroke Treatment,TOAST)分型,于发病(10±2)d进行蒙特利尔认知量表(Montreal Cognitive Assessment,Mo CA)、临床痴呆量表(Clinical Dementia Rating,CDR)、日常生活能力量表(Activities of Daily Living,ADL)评分,依据血管性认知障碍诊治指南中VCI的诊断及分类诊断标准将患者分为认知正常组(no cognitive impairment,NCI)和VCI组,VCI组包括VCIND组和Va D组,分析上述各项因素的组间差异及相关性。结果 491例急性缺血性卒中患者中VCI占69.86%,其中包括37.68%的VCIND和32.18%的Va D患者。1VCI组低受教育程度(P0.001)、糖尿病(P=0.005)、心脏病(P=0.045)、卒中家族史(P=0.005)、幕上病变(P0.001)的比例及卒中次数(P=0.014)、D-二聚体水平(P=0.001)、Essen评分(P=0.024)、NIHSS评分(P0.001)显著高于NCI组,女性(P=0.004)、幕下病变(P0.001)的比例及受教育年(P0.001)显著低于NCI组,差异均有显著性;Logistic回归分析显示低受教育程度、糖尿病、幕上病变和高D-二聚体水平是VCI的独立危险因素。2与VCIND组比较,Va D组患者既往卒中史(P=0.013)、TOAST分型中大动脉粥样硬化型梗死(P0.001)的比例及卒中次数(P=0.001)、Essen评分(P=0.032)、神经功能缺损程度(P=0.005)显著高于VCIND组,TOAST分型中小动脉闭塞型梗死(P0.001)、幕下病变(P0.001)的比例显著低于VCIND组,差异均有显著性;Logistic回归分析显示卒中次数、神经功能缺损程度、大动脉粥样硬化型梗死是Va D的独立危险因素,而幕下病变患者发生Va D的风险明显小于幕上病变患者。结论 VCI及其亚型的影响因素不同,与NCI比较,低受教育程度、糖尿病、幕上病变和高D-二聚体水平是VCI的独立危险因素;与VCIND比较,卒中次数、严重的神经功能缺损、TOAST分型中大动脉粥样硬化型梗死是Va D的独立危险因素。     

脑心通治疗血管性认知障碍的临床研究

目的评价脑心通胶囊治疗血管性认知障碍的临床疗效和安全性。方法本研究从三个分中心招募血管性认知功能障碍(VCI)患者240例,并随机分为治疗组121例,其中无痴呆血管认知功能障碍(VCIND)患者45例,血管性痴呆(VaD)患者76例;对照组120例,其中VCIND患者44例,VaD患者76例。治疗组给予脑心通胶囊每日口服3次,每次4粒;对照组给予复方丹参片每日口服3次,每次4粒,连续服用3月。比较不同阶段的VCI患者治疗前后简易智能精神状态量表(MMSE)、日常生活能力量表(ADL)的变化。结果治疗组VCIND患者治疗后MMSE和ADL评分均有明显改善,差异有统计学意义(P<0.01)。治疗组VaD患者治疗后MMSE略有改善,差异无统计学意义(P>0.05),而ADL评分有改善,差异有统计学意义(P<0.01)。结论脑心通胶囊能够改善无痴呆血管性认知障碍(VCIND)患者的认知功能。     

Therapeutic issues in vascular dementia: studies, designs and approaches

Vascular dementia (VaD) is a heterogeneous disorder resulting from various cerebrovascular diseases (CVD) causing cognitive impairment that reflects severity and location of damage. Epidemiological studies suggest VaD is the second commonest cause of dementia, but autopsy series report that pure VaD is infrequent, while combined CVD and Alzheimer's Disease(AD) is likely the commonest pathological-dementia correlate. Both diseases share vascular risk factors and benefit from their treatment. The most widely used diagnostic criteria for VaD are highly specific but not sensitive. Vascular Cognitive Impairment (VCI) is a dynamic, evolving concept that embraces VaD, Vascular Cognitive Impairment No Dementia (VCIND) and mixed AD and CVD. Clinical trials to date have focused on probable and possible VaD with beneficial effects evident for different drug classes, including cholinergic agents and NMDA agonists. Limitations have included use of cognitive tools suitable for AD that are insensitive to executive dysfunction. Disease heterogeneity has not been adequately controlled and subtypes require further study. Diagnostic VaD criteria now 13 years old need updating. More homogeneous subgroups need to be defined and therapeutically targeted to improve cognitive-behavioural outcomes including optimal control of vascular risk factors. More sensitive testing of executive function outlined in recent VCI Harmonization criteria and longer trial duration are needed to discern meaningful effects. Imaging criteria must be well-defined, with centralized review and standardized protocols. Serial scanning with quantification of tissue atrophy and lesion burden is becoming feasible, and cognitive interventions, including rehabilitation pharmacotherapy, with drugs strategically coupled to cognitive -behavioural treatments, hold promise and need further development.     

血管性认知功能障碍及痴呆患者血浆内皮素-1和血管内皮生长因子含量变化及意义

目的探讨血浆内皮素-1（ET-1）和血管内皮生长因子（VEGF）在血管性认知功能障碍（VCI）及痴呆（VaD）发病过程中的作用。方法脑梗死143例,随访3个月,依据蒙特利尔认知评估量表（MoCA）和临床痴呆评定量表（CDR）评分将其分为无认知功能障碍（N-VCI）组、血管性认知障碍无痴呆（VCIND）组、血管性痴呆（VaD）组,用放射免疫法测定血浆ET-1水平,酶联免疫分析法测定血浆VEGF的水平,并对血浆ET-1和VEGF进行相关性分析。结果 （1）VaD组患者血浆ET-1含量明显高于VCIND组及N-VCI组,VCIND组患者血浆ET-1水平明显高于N-VCI组,差异均具统计学意义（P〈0.01）;VaD组患者血浆VEGF含量明显低于VCIND组及N-VCI组,VCIND组亦明显低于N-VCI组,差异均具统计学意义（P〈0.01）。（2）血浆ET-1水平与VEGF存在明显负相关（r=-0.808,P〈0.01）。（3）VaD组患者血浆ET-1与MoCA值成负相关（r=-0.719,P〈0.01）,VaD患者血浆VEGF与MoCA评分成正相关（r=0.670,P=0.01）;而N-VCI、VCIND组患者血浆ET-1、VEGF与MoCA值无相关性（P〉0.05）。结论高ET-1和低VEGF参与了VCI及VaD的发生发展过程,血浆ET-1与VaD病情成正相关,血浆VEGF与VaD病情成负相关,这些指标的监测可作为判断VaD病情轻重的重要依据。     

Vascular cognitive deterioration and stroke

Vascular cognitive impairment, the recent modification of the terminology related to vascular burden of the brain, reflects the all-encompassing effects of vascular disease or lesions on cognition. It incorporates the complex interactions between vascular aetiologies, risk factors and cellular changes within the brain and cognition. The concept covers the frequent poststroke cognitive impairment and dementia, as well as cerebrovascular disease (CVD) as the second most common factor related to dementia. CVD as well as vascular risk factors including arterial hypertension, history of high cholesterol, diabetes or forms of heart disease are independently associated with an increased risk of cognitive impairment and dementia. Traditional vascular risk factors and stroke are also independent factors for the clinical presentation of Alzheimer's disease (AD). In addition to these vascular factors, CVD/strokes, infarcts and white-matter lesions may trigger and modify the progression of AD as the most common cause of neurodegenerative dementia. The main subtypes of previously defined vascular dementia (VaD) include the cortical VaD or multi-infarct dementia also referred as poststroke VaD, subcortical ischaemic vascular disease and dementia or small-vessel dementia and strategic-infarct dementia. Whilst CVD is preventable and treatable, it is clearly a major factor in the prevalence of cognitive impairment in the elderly worldwide.     

Neuroprotection in vascular dementia

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD), and one of the major causes of mental and physical disability in developed countries. As such, the identification and implementation of strategies which prevent the development of the condition or enable improvements in patients with VaD are healthcare objectives of the first order. VaD is now regarded as a combined group of clinical-pathological entities rather than one disease, that is, multiple pathogenic mechanisms and lesion types underlie a cognitive impairment of vascular origin. The clinical diagnosis of VaD is complex and difficult because of the heterogeneous nature of its clinical presentation and progression and the low sensitivity of existing clinical criteria. Moreover, there is growing evidence of the epidemiological significance of mixed forms of dementia, and that ischemic processes may precipitate and exacerbate cognitive impairment in AD. Numerous compounds have been proposed as potentially useful in the treatment of patients with VaD, comprising vasodilatative, antithrombotic, hemorrheological, nootropic, antiserotoninergic and, most recently, antiglutamatergic and cholinergic approaches. In spite of some initially favorable reports based on the use of memantine, donepezil and galantamine, there is as yet no conclusive evidence of a definitive treatment for VaD. Unsatisfactory results from VaD drug trials may be attributed in part to the diversity of the patients included (underlying pathogenic mechanisms, number, type, and location of vascular lesions), and to methodological limitations in the design of the trials (outcome measures, end-points, size, follow-up period). The treatment of modifiable vascular risk factors - hypertension, diabetes mellitus, hypercholesterolemia and heart disease - is an important strategy for the reduction of the risk of dementia, and is likely to slow the progress of cognitive decline.