皮质下缺血性脑血管病的神经心理学改变

概述皮质下缺血性脑血管病(subcortical ischemic vascular diseases,SIVD)是造成血管性认知功能损害(vascular cognitive impairment,VCI)的重要原因,它所导致的认知损害是VCI中具有同质性和最为常见的亚型(皮质下型VCI)。VCI覆盖了从轻微的     

皮层下缺血性血管性痴呆

皮层下缺血性血管性痴呆（subcortical ischemic vascular dementia, SIVD）是血管性认知障碍（Vascular cognitive impairment, VCI）的一个亚型,具有认知障碍和皮层下脑缺血病灶的证据。其包括腔隙状态、关键部位梗死性痴呆和Binswanger综合征等3个类型。认知障碍的特征是显著的执行功能障碍和相对轻微的工作记忆减退。对脑血管病危险因素的干预有助于皮层下缺血性血管性痴呆的防治。     

非痴呆性血管性认知障碍的研究进展

血管性认知障碍（vascular cognitive impairment,VCI）是由脑血管病危险因素（如高血压、 糖尿病、高脂血症和高同型半胱氨酸血症等）、显性脑血管病（出血性及缺血性卒中）及非显性脑血 管病（脑白质疏松和慢性脑缺血等）引起的一组从轻度认知功能损害到痴呆的临床综合征。非痴呆 性血管性认知障碍（vascular cognitive impairment-no dementia,VCIND）是VCI的早期阶段,其中约一半 患者会在5年内进展为痴呆。血管性痴呆（vascular dementia,VD）在治疗上尚未发现行之有效的方法, 但又是唯一可以预防的痴呆。发现VCIND危险因素并进行早期干预,对于寻求延缓痴呆进展的二级 预防策略至关重要。现从VCIND的概念、流行病学、诊断标准及影响因素等方面进行综述,以期能够 早期识别相关危险因素,防治VCI。     

阻塞性睡眠呼吸暂停低通气综合征对皮质下缺血性脑血管病病理机制的可能影响

阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome, OSAHS)是一种常见的且可导致多系统损伤的疾病，间歇性低氧和碎片化睡眠引起的低灌注、炎性反应等病理机制可造成认知功能损害，继而严重影响患者生活质量。皮质下缺血性脑血管病(subcortical ischemic vascular disease, SIVD)属于血管性认知障碍(vascular cognitive impairment, VCI)的重要亚型，常见于老年人，早期临床症状隐匿，易被忽视，贻误最佳治疗时期。现就OSAHS引起的间歇性低氧、低灌注损伤、内皮功能障碍、神经炎症、睡眠结构紊乱等在SIVD病理机制中的可能作用进行综述，以期为临床治疗和预防提供帮助。     

血管性认知损害

血管性痴呆是发生在中老年人群中最常见的痴呆之一，近年来在深入研究该病防治的基础上，又提出了血管性认知损害（vascular cognitive impairment，VCI）这一新术语。认为深入研究VCI，有助于对血管性因素和血管病引起的认知损害或痴呆的理解以及早期诊断和早期治疗。本文就VCI的有关研究进展做一介绍。     

皮质下脑梗死所致血管性认知障碍患者认知功能与脑白质病变的相关性研究

目的 分析皮层下脑梗死所致血管性认知障碍 （subcorticalvascular cognitive impairment, SVCI） 脑白质 变性与认知功能评分的相关性。 方法 连续入组皮层下脑梗死患者91例, 根据神经心理学蒙特利尔认知评估 （Montreal Cognitive Assessment, MOCA） 分为皮层下脑梗死所致血管性认知障碍 （subcortical vascular cognitive impairment, SVCI） 组 （49例） 和无认知障碍的皮质下梗死 （subcortical infarcts, SI） 组 （42例） , 分析其临床、 认知 障碍、 神经影像学特征, 并探讨认知障碍与白质损伤的相关性。 结果 SVCI组糖尿病发病率高于SI组 （38.78% vs 16.67%, P =0.02） , SVCI组脑白质病变患者37 例 （75.51%） 。 脑白质损害程度与MOCA执行功能 （ Rs =-0.415, P =0.028） 、 瞬时记忆 （ Rs =-0.577, P =0.001） 、 注意 （ Rs =-0.382, P =0.001） 、 延迟记忆 （ Rs =-0.389, P =0.041） 等4个分量表以及MOCA 量表总分 （ Rs =-0.495, P =0.002） 成负相关。 结论 SVCI患者糖尿病比例高于SI患者, 白质病变多见, 且白质病变的程度可以反映不同程度的认知 损害。     

皮质下血管性轻度认知障碍患者的多模式磁共振研究

目的 明确对皮质下缺血性血管病（subcortical ischemic vascular disease,SIVD）患者早期认知损害较 为敏感的磁共振成像（magnetic resonance imaging,MRI）指标。 方法 32例SIVD患者经过认知测试,被分为无认知障碍（no cognitive impairment,NCI）组18例,血管性 轻度认知障碍（vascular mild cognitive impairment,VaMCI）组14例,分析其认知测试指标与MRI参数之间 的关系。 结果 NCI组、VaMCI组全脑白质（whole brain white matter,WBWM）平均弥散度（mean diffusivity,MD） 分别为（0.84±0.03）×10-9·m2·s-1和（0.89±0.05）×10-9·m2·s-1,表观正常白质（normal appearing white matter,NAWM）的MD分别为（0.87±0.04）×10-9·m2·s-1和（0.92±0.05）×10-9·m2·s-1,差异 均有显著性（P均为0.003）;NCI组、VaMCI组WBWM各向异性分数（fractional anisotropy,FA）分别为 （0.37±0.02）和（0.35±0.02）,两组有显著差异（P =0.002）,两组NAWM的FA分别为（0.35±0.02）和 （0.33±0.02）,差异亦有显著性（P =0.001）。SIVD患者WBWM的MD值、NAWM的MD值和FA值与注意- 执行均相关,相关系数分别为－0.401（P =0.031）、－0.422（P =0.023）和0.409（P =0.027）,NAWM的 MD值与记忆相关,相关系数为－0.377（P =0.044）,多元逐步回归显示仅NAWM的MD值与注意-执行 （β=－0.453,P =0.009）、记忆（β=－0.414,P =0.019）和总体认知（β=－0.410,P =0.02）独立负相 关。而常规MRI参数未显示组间差异,与认知功能亦未见相关性。 结论 MRI弥散张量成像（diffusion tensor imaging,DTI）可以作为早期识别SIVD患者认知障碍的有效 手段。NAWM的MD值在认知障碍早期即下降,并与多项认知域独立相关,是较为敏感的DTI指标。     

皮质下缺血性抑郁和皮质下缺血性痴呆患者的抑郁症状分析

目的 比较皮质下缺血性抑郁和皮质下缺血性痴呆患者的抑郁症状。方法 连续收集2008年9月至2011年3月间符合入选标准的70例皮质下缺血性血管病（subcortical ischemic vascular disease,SIVD）患者,根据抑郁和痴呆的诊断标准及17项版汉密尔顿抑郁量表（Hamilton Rating Scale of Depression,HRSD）和简易智能状态检查（Mini-Mental State Examination,MMSE）分为无抑郁或痴呆组（29例）、抑郁组（19例）、痴呆组（12例）、抑郁伴痴呆组（10例）。应用HRSD对各组患者的抑郁症状进行评价,分析比较各组患者的抑郁症状的表现特点。结果 4组患者的年龄、性别比、社会经济因素及血管性危险因素的差异无统计学意义。就发生率,抑郁组以抑郁情绪（17例,89.5%）、精神性焦虑（16例,84.2%）、躯体性焦虑（15例,78.9%）最突出,而痴呆组和抑郁伴痴呆组以阻滞（8例,66.6%和9例,90.0%）最突出。就严重程度,除睡眠障碍外,抑郁组以焦虑躯体化症状[0.8（0.2,2）]最严重,而痴呆组和抑郁伴痴呆组以阻滞症状［1（0.3,1.8）和1.1（0.3,2）］最严重。抑郁组的抑郁程度较抑郁伴痴呆组更高（P=0.026）、焦虑躯体化更突出（P<0.01）。结论 皮质下缺血性抑郁和皮质下缺血性痴呆及两者共存的患者的情绪损害特点存在着差异,皮质下缺血性抑郁较偏向于经典抑郁症所致情绪障碍,皮质下缺血性痴呆和皮质下缺血性抑郁伴皮质下缺血性痴呆的患者则较偏向于皮质下缺血性病变所致情绪障碍。     

轻度认知障碍与无痴呆型血管性认知障碍患者的神经心理学特征

阿尔茨海默病（AD）和血管性痴呆（vascular dementia，VD）是临床常见的老年期痴呆类型。虽然长期以来受到广泛关注．但对其治疗收效甚微．近年逐渐将研究重点转向对其早期阶段的干预治疗。在这一临床需要下，针对阿尔茨海默病和血管性痴呆分别提出了轻度认知障碍（mild cognitive impairment，MCI）和血管性认知障碍（vascular cognitive impairment，VCI）的概念，力求对患者进行早期识别和干预，以延缓甚至阻止痴呆的发生、发展。     

皮质下缺血性脑血管病的临床特点和危险因素

目的 研究皮质下缺血性脑血管病（SIVD）在缺血性卒中患者中的发病率、临床特点和危险因素。方法 门诊连续登记的526例发病3个月后的卒中患者入选该研究。对入选患者进行多种神经心理学和功能量表评定以及神经影像学评估,并记录人口学资料、卒中临床特点和血管危险因素。结果 526例患者中,SIVD患者110例（20.9%）,其中男性占61.8%,平均年龄66.8±10.5岁。高血压是最常见的危险因素（80.0%）,其次是血脂异常和吸烟史,分别为52.7%和40.9%,有57.3%的患者有2个以上的危险因素。32.7%的患者有抑郁障碍。用Lawton FAQ量表评定显示工具性日常生活能力下降的SIVD患者53人（48.0%）,用Barthel 指数（BI）测定显示日常生活能力下降者14人（12.8%）。49例（44.5%）有血管性认知功能损害,其中26例（23.6%）符合血管性痴呆标准。结论 缺血性卒中患者中,SIVD约占1/5,SIVD患者认知损害、抑郁、工具性日常生活能力受累较常见,并伴有多种危险因素。     

Clinical features of MRI-defined subcortical vascular disease

BACKGROUND AND PURPOSE: Vascular cognitive impairment and vascular dementia are now seen to extend much beyond the traditional multi-infarct dementia.A more homogeneous subtype is the subcortical ischemic vascular disease (SIVD). We applied magnetic resonance imaging (MRI) criteria based on research criteria for SIVD in a large cohort of patients with ischemic stroke. We compared clinical features of patients with SIVD and patients with other stroke type. SUBJECT AND METHODS: The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery and MRI, including structured medical, neurologic, and laboratory evaluations; clinical mental status examination; interview of a knowledgeable informant; detailed history of risk factors; and evaluation of stroke type, localization, and syndrome. RESULTS: Patients with SIVD (n = 86) more often had a history of progressive cognitive decline (22.8% vs. 6.9%, P = 0.0002), walking disorder before stroke (27.9% vs. 2.0%, P = 0.02), and urinary difficulties (12.8% vs. 5.6%, P = 0.028) in comparison with patients with other stroke type (n = 251). Of the study population, 107 (31.8%) had DSM-III dementia. The patients with SIVD more often had DSM-III dementia (40.7% vs. 28.7%, P = 0.04), had less severe stroke as measured by Scandinavian Stroke Scale (56.6 vs. 55.1, P = 0.03), were more dependent in activities of daily living (ADL) functions as measured by FAQ scale (8.9 vs. 5.4, P = 0.001), were more dependent in instrumental activities of daily living (IADL) functions as measured by the Lawton scale (5.5 vs. 6.3, P = 0.01), and were more depressed as measured by the Beck Depression Inventory (11.8 vs. 8.4, P = 0.0003) poststroke than the patients without SIVD. The main cognitive domain that differentiated the patients with SIVD from those without was executive dysfunction (51.2% vs. 38.7%, P = 0.04). According to multiple regression model, apractic-atactic gait disorder (odds ratio 2.82, 95% confidence interval 1.21-6.53), ADL functions (odds ratio 1.04, 95% confidence interval 1.01-1.08), and the Beck Depression Inventory (odds ratio 1.05, 95% confidence interval 1.02-1.09) related to SIVD. CONCLUSIONS: The most significant clinical features of MRI-defined SIVD were found to be apractic-atactic gait, impaired ADL functions, and depression.     

不同类型的血管性认知损害的执行功能障碍

目的 分析不同类型的血管性认知功能损害(VCI)患者的执行功能损害特征.方法 经头颅MRI证实为皮质下缺血性小血管病(SIVD)患者64例,其中16例单一的执行功能损害(s-VCI-ND)、26例多个认知领域损害(m-VCI-ND)和22例血管性痴呆(VaD)患者,完成一系列神经心理测验,包括总体认知水平、记忆、语言、注意/执行功能、空间结构能力等各个认知领域.其中执行功能检查包括定势转移、优势抑制、工作记忆、概念形成和流畅性5个分因子,共15种独立的分测验.结果 汉诺塔测验、示踪排序测验、同步听觉连续加法测验等在非痴呆VCI(VCI-ND)患者中的完成率低于50%,不适合VCI-ND的检测;s-VCI-ND组与健康对照组比较,分别反映4种执行功能成分的连线测验B耗时数(216.5±69.3、137.4±37.9)、Stroop色词测验卡片C耗时数(115.4±30.1、72.9±17.5)、卡片分类测验(1.9±1.4、2.7±1.2)和范畴流畅性测验(列举动物14.2±2.3、17.7±4.4)差异具有统计学意义(t=4.73、5.72、2.04、3.53,均P<0.05);VCI-ND的认知表现介于健康老人组和VaD组之间,其中m-VCI-ND有比较严重的执行功能损害和情景与语义记忆障碍,其认知缺损模式接近VaD,很可能是VaD的前期状态.结论 SIVD所致VCI的执行功能损害缺乏选择性,部分执行功能测验可以作为早期检测VCI-ND的敏感工具.     

Validation study of a CT-based weighted rating scale for subcortical ischemic vascular disease in patients with mild cognitive deterioration

OBJECTIVES: Subcortical ischemic vascular disease (SIVD) is frequently associated with cognitive impairment. Rating scales to grade cerebrovascular disease are available, but their sensitivity to the clinical features of mild SIVD is unclear. The aim of the study is to devise and validate a computed tomography (CT)-based visual rating scale sensitive to SIVD in patients with mild cognitive deterioration. METHODS: Subjects were 122 consecutive outpatients of a memory clinic (mean age +/- SD 77 +/- 8 years, 71% females, mean +/- SD score of mental state exam 22 +/- 3, 61% with clinical dementia rating of 0.5 and 39% of 1). Diffuse leukoaraiosis, fuzzy and patchy lesions, and lacunes were assessed on ordinary CT films and weights were computed based on clinical indicators of SIVD. A continuous score and an ordinal class (0-3) with higher values indicating higher vascular damage were derived. RESULTS: Intraclass correlation coefficients for intra- and interrater reliability of the subcortical vascular score and class ranged from 0.84 to 0.88. Convergent validity versus the scale of Wahlund et al. was good (Spearman's correlation coefficient between 0.53 and 0.73, p < 0.0005). Known-group validity was assessed versus clinical diagnoses of degenerative (mild cognitive impairment determined by Petersen et al. and NINCDS-ADRDA probable Alzheimer's disease; n = 58), mixed (possible Alzheimer's disease with cerebrovascular disease; n = 21), and vascular cognitive impairment (criteria of Erkinjuntti et al. for subcortical vascular dementia and cognitive impairment; n = 43). Patients with degenerative cognitive impairment were more often in the lower subcortical vascular classes (43% in class 0, 43% in class 1, 14% in class 2, and 0% in class 3), while patients with mixed (0, 24, 24, and 52%) and vascular cognitive impairment were in increasingly higher subcortical vascular classes (0, 12, 35, 53%; p < 0.00005). Criterion-related validity was assessed versus clinical indicators of cerebrovascular disease. Hypertension, platelet aggregation inhibitor use, balance, gait, and bradykinesia increased linearly with increasing subcortical vascular class (p for trend <0.02). CONCLUSIONS: This rating scale is valid and sensitive to capture different degrees of SIVD associated with mild cognitive deterioration.     

The auditory oddball paradigm in patients with vascular cognitive impairment: a prolonged latency of the N2 complex

OBJECTIVE: The event-related potential (ERP) evoked by the auditory oddball paradigm has been investigated mainly in patients with Alzheimer's disease and in patients with different causes of subcortical dementia. Subcortical ischemic vascular disease (SIVD) seems to be an important cause of vascular cognitive impairment (VCI) frequently not fulfilling the criteria for dementia. Recognition of VCI is needed in order to provide adequate care and therapy. The aim of this study was to investigate the diagnostic value of the different elements of this response (N(1), N(2) complex and P(3) latencies) in a group of elderly patients with VCI caused by SIVD. METHODS: The study population consisted of patients with a clinical and neuropsychological diagnosis of VCI caused by SIVD (n = 38) and healthy control subjects (n = 53) aged 60 years or older. The mean Mini Mental State Examination score of both groups was 27.6, and the mean HIV Dementia Scale score was 6.1 in the patient group and 12.3 in the control group. In all subjects, the ERP was recorded under standardized conditions, and the latencies and amplitudes of N(1), N(2) and P(3) were analyzed by two clinical neurophysiologists in consensus. Both were blinded to the diagnosis. RESULTS: The N(2) latency was significantly longer in patients with VCI than in age-matched controls, whereas the latencies of the P(3) and N(1) were not significantly different. The peak-to-peak amplitude of the N(2) complex to the P(3) wave was significantly lower in the patient group. White matter abnormalities on MRI were not significantly correlated with the N(2) latency. CONCLUSION: Our findings suggest that the latency of the N(2) complex is prolonged and the peak-to-peak amplitude of the N(2) complex to the P(3) wave is lowered in patients with VCI caused by SIVD.     

皮质下缺血性血管性认知损害患者注意功能障碍的临床研究

目的:观察皮质下缺血性血管性认知功能损害(SIVCI)患者注意亚型障碍的特征。方法:对30例非痴呆型SIVCI(SIVCIND)患者(SIVCIND组)、15例皮质下缺血性血管性痴呆(SIVD)患者(SIVD组)和15名健康志愿者(对照组)采用计算机上持续操作任务(CPT)、Stroop试验及双任务测试法测试持续注意、选择注意和分散注意功能。结果:与对照组比较,SIVD组CPT反应时延长,漏报率增加(P<0.05);SIVCIND组漏报率与对照组比较显著增加,差异有显著统计学意义(P<0.01)。SIVD患者冲突及中性条件下,反应时与错误率及干扰量均增加;SIVCIND患者Stroop试验冲突条件反应时延长(P<0.01)、双任务法耗时差无明显增加(P>0.05);SIVD患者耗时差增加(P<0.01)。结论:SIVCIND早期主要以持续:注意及选择注意功能损害为主,晚期则持续注意、选择注意和分散注意功能普遍受累。     

血管性认知功能障碍患者经颅多普勒超声血流动力学变化与认知功能的关系

目的探讨轻度血管性认知功能障碍(m VCI)患者TCD血流动力学变化与认知功能的关系。方法依据Erkinjuntti的MRI诊断标准入选的皮质下缺血性血管病(SIVD)患者115例,根据神经心理学评估分为血管性认知障碍(VCI)组和认知正常组。使用经颅多普勒超声(TCD)进行颅内血流动力学检查。最后分析患者的Mo CA评分与大脑中大动脉(MCA)和大脑前动脉(ACA)的搏动指数(PI)、平均血流(Vm)的相关性。结果对于两组患者的MCA-PI和ACA-PI进行比较,差异具有统计学意义(P0.05);而两组患者之间的MCA-Vm和ACA-Vm比较,差异无统计学意义(P0.05)。MCA-PI和SIVD患者的认知损害呈线性相关,回归方程Y=38.783-7.823 X_1,差异有统计学意义(P0.01)。结论 MCA-PI与SIVD患者Mo CA评分线性相关。SIVD患者的PI越高,相对应其认知障碍程度越严重。     

皮质下缺血性脑血管病白质改变与认知损害初探

目的:对皮质下缺血性脑血管病(SIVD)的临床特征、认知和MRI白质改变进行分析,初步探讨SIVD患者认知损害与MRI白质改变的关系。方法:经过访谈和详细查体,记录患者症状和体征,进行神经心理学评估并行头MRI扫描。依据Erkinjuntti提出MRI诊断标准确定SIVD患者29例。结果:认知正常者、血管性CIND患者和VaD患者的MMSE得分分别为(27.5±1.84)、(23.7±2.06)和(18±1.58)。随着认知功能损害程度的加重,其白质改变的评分增加,具有统计学显著差异。结论:SIVD患者的认知功能损害与其白质改变程度有关。     

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.     

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。