Neurobehavioral dysfunction in patients with subcortical vascular mild cognitive impairment and subcortical vascular dementia

Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.     

磁共振弥散张量成像对预测皮质下缺血性血管性痴呆患者认知功能障碍的价值

目的应用磁共振弥散张量成像(DTI)技术,探讨皮质下缺血性血管性痴呆(SIVD)患者不同联络纤维感兴趣区弥散张量参数改变与认知功能的关系。方法对60例SIVD患者和40例年龄匹配的非痴呆对照者,采用测定感兴趣区弥散张量参数的方法,比较其纤维束完整性差异及与神经心理学量表的关系。结果 (1)与对照组比较,SIVD组双侧下额枕束、双侧扣带束、左侧上纵束和胼胝体膝部的FA值显著下降及ADC值显著升高;(2)双侧额叶前部皮质下白质FA值与MMSE及Mo CA评分呈明显正相关;(3)双侧海马区、双侧扣带束的FA值与MMSE评分呈明显正相关。结论不同脑区的弥散张量参数变化特点有助于SIVD患者认知功能障碍的早期预测。     

Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly. METHODS: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH. RESULTS: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005). CONCLUSIONS: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory.     

The relationship of MRI subcortical hyperintensities to treatment response in a trial of sertraline in geriatric depressed outpatients.

The authors examined differences in antidepressant treatment response in geriatric outpatients with high vs. low levels of magnetic resonance imaging (MRI)-defined subcortical hyperintensities (SH). Participants included 59 outpatients with mild-to-moderate depression (mean age: 69+/-5.63 years; mean Hamilton Rating Scale for Depression score: 21+/-2.88) who participated in a placebo-controlled trial of sertraline and underwent a standardized brain MRI. Results revealed that the high-SH group was significantly older than the low-SH group but, contrary to the hypothesis, antidepressant treatment response did not differ between the high- and low-SH groups. The association between SH and antidepressant treatment response in depressed geriatric outpatients remains unclear and deserves further investigation.     

Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia

BACKGROUND: There are inconsistencies in published reports regarding the profile of cognitive impairments in vascular dementia, and its differentiation from Alzheimer's disease. OBJECTIVES: To identify the overall profile of cognitive impairment in subcortical vascular dementia as compared with Alzheimer's disease; and the tests which best discriminate between these groups. METHODS: 57 subjects participated: 19 with subcortical vascular dementia, 19 with Alzheimer's disease, and 19 controls. The dementia groups were matched for age, education, and general levels of cognitive and everyday functioning. Subcortical vascular dementia was defined by clinical features (prominent vascular risk factors plus a previous history of transient ischaemic events or focal neurological signs) and substantial white matter pathology on magnetic resonance imaging. All subjects were given a battery of 33 tests assessing episodic and semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. RESULTS: Despite a minimal degree of overall dementia, both patient groups had impairments in all cognitive domains. The Alzheimer patients were more impaired than those with vascular dementia on episodic memory, while the patients with vascular dementia were more impaired on semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. Logistic regression analyses showed that the two groups could be discriminated with 89% accuracy on the basis of two tests, the WAIS logical memory--delayed recall test and a silhouette naming test. CONCLUSIONS: Subcortical vascular dementia and Alzheimer's disease produce distinctive profiles of cognitive impairment which can act as an adjunct to diagnosis. Many of the neuropsychological deficits thought to characterise Alzheimer's disease are also found in subcortical vascular dementia.     

The relationship between microvasculature in white matter hyperintensities and cognitive function

White matter hyperintensities (WMHs) are associated with cognitive decline, but less is known about pathophysiology of cognitive decline in patients with WMHs. We investigated microvasculature and microstructure in WMHs using intravoxel incoherent motion (IVIM) and their associations with cognitive function. Thirty-two subjects with WMHs were enrolled in our study. Fast diffusion coefficient (D*), perfusion fraction (f) and slow diffusion coefficient (D) from IVIM model were compared between regions of WMHs (periventricular WMHs, PWMHs and deep WMHs, DWMHs) and surrounding normal white matter. Multivariate linear model was used to determine the independent factors associated with cognitive function assessed by the Mini Mental State Examination (MMSE) and the standardized coefficient (β) of factors was estimated. D* was significantly lower (4.95?×?10^?3 mm²/s versus 8.36?×?10^?3 mm²/s in PWMHs and 5.04?×?10^?3 mm²/s versus 8.67?×?10^?3 mm²/s in DWMHs, both P?<?0.001), and f (14.64 % versus 12.01 % in PWMHs and 14.26 % versus 11.31 % in DWMHs, both P?<?0.001) and D (1.02?×?10^?3 mm²/s versus 0.73?×?10^?3 mm²/s in PWMHs and 0.86?×?10^?3 mm²/s versus 0.70?×?10^?3 mm²/s in DWMHs, both P?<?0.001) were significantly higher in WMHs. Only f in PWMHs was independently associated with MMSE (β?=?0.443, P?=?0.016). The decreased D* and increased D in WMHs were similar to previous findings. The increased f in PWMHs relating with better cognition provides the pathophysiological basis in understanding cognitive decline in patients with WMHs.     

The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function

BACKGROUND: Hypertension at the age of 45 to 50 years may predispose to AD later in life. It is not known whether hypertension after age 65 years also contributes to AD risk, and its effect on cognitive function is also not fully understood. METHODS: Data were analyzed from 1,259 Medicare recipients free of dementia in a longitudinal study covering a 7-year period (1991 to 1998). The effect of hypertension was first examined in relationship to the risk for incident AD and then to incident vascular dementia (VaD) using Cox proportional hazards models. Changes in performance over time on tasks of memory, language, and visuospatial/cognitive function were compared in those with and without hypertension using generalized estimating equations. RESULTS: Of the 1,259 subjects, 731 (58.1%) had a history of hypertension associated with diabetes, stroke, and heart disease. A history of hypertension was not associated with an increased risk for AD (rate ratio [RR] 0.9, 95% CI 0.7 to 1.3) but was associated with an increased risk for VaD (1.8 [1.0 to 3.2]). Hypertension was not associated with changes in memory, language, and general cognitive function in normal individuals over time. Compared with individuals with neither hypertension nor heart disease, those with hypertension or heart disease alone had no increase in risk for VaD. However, when both were present, there was a threefold increase in risk for VaD. A sixfold increase in risk was observed when both hypertension and diabetes were present. CONCLUSIONS: Hypertension after age 65 years is not associated with AD and does not adversely affect memory, language, or general cognitive function. A history of hypertension may be an antecedent to VaD, particularly in the presence of heart disease or diabetes.     

Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia. DESIGN: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean. SETTING: General community. PATIENTS: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI). MAIN OUTCOME MEASURES: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at baseline). Cox proportional hazards models were used for multivariable analysis. RESULTS: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P= .01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P= .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P< .001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P= .03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P= .02), but not AD dementia. CONCLUSIONS: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.     

皮质下缺血性脑血管病MRI与血管性痴呆的相关性研究

目的:探索皮质下缺血性脑血管病MRI表现与血管性痴呆之间的关系。方法:对比分析了皮质下多发梗死28例痴呆患者和33例非痴呆患者的MRI表现,采用Logistic回归分析皮质下缺血性血管性痴呆的影像学相关高危因素。结果:痴呆组中顶叶皮质下、内囊膝部和丘脑的梗死发生率,顶叶皮质下、侧脑室体旁前部、内囊膝部和丘脑平均梗死数目,4级LA的出现率以及所有脑萎缩指标均明显大于对照组(P<0.05)。但Logistic回归后,只有平均脑沟宽度、侧脑室指数和丘脑梗死的数目进入了方程。结论:皮质下缺血性血管性痴呆可能与脑萎缩的程度和丘脑梗死的数目密切相关。     

皮质下血管性痴呆患者脑注意和执行功能区激活特征及与认知功能损害的相关性

目的 分析皮质下血管性痴呆( subcortical ischemic vascular dementia,SIVD)患者脑注意和执行功能区激活特征及其与认知功能损害的相关性.方法 SIVD患者20例,健康对照组20名,按年龄、性别、文化层次进行配对.采用Stroop任务和SEMENTS 3.0T MRI仪行功能MRI,将脑功能区激活表现与认知功能损害特征进行相关分析.结果 SIVD患者双侧背外侧前额叶、腹外侧前额叶和后顶叶激活体积均与MoCA总分、视空间与执行、注意、语言、延迟回忆、定向分项得分明显相关(r =0.447～0.837,P＜0.05).结论 Stroop任务引起的功能MRI脑激活图可以反映SIVD患者认知功能的损害.     

Motor intentional disorders in vascular mild cognitive impairment and vascular dementia of subcortical type

Subcortical vascular mild cognitive impairment (svMCI), a prodromal stage of subcortical vascular dementia (SVaD), is primarily associated with frontal injuries, whereas amnestic MCI (aMCI) is associated with temporoparietal injuries. Twenty-seven patients with svMCI, 20 with aMCI, 14 with SVaD, and 10 normal controls underwent motor intentional tasks (force initiation, development, maintenance, and termination) using a force dynamometer. Of the four motor intentional tasks, the maintenance task proved sensitive in differentiating svMCI from aMCI. In most motor intentional tasks, performances of svMCI patients were intermediate between those of controls and SVaD patients (initiation and termination: NC=aMCI=svMCI>SVaD; development: NC>aMCI=svMCI>SVaD; maintenance: NC=aMCI>svMCI=SVaD).     

The role of brain infarcts and hippocampal atrophy in subcortical ischaemic vascular dementia

Abstract. We investigated if, in patients with vascular lesions, the variable that best discriminated demented from non–demented patients was the severity of the vascular pathology or the degree of hippocampal atrophy. A total of 39 patients multiple subcortical infarcts, who could be considered as possible vascular dementia with small vessel pathology, with underwent a neuropsychological study and brain magnetic resonance imaging (MRI) DSM IV criteria supported by neuropsychological data were used to distinguish demented from non–demented patients. The MRI study took into account the degree of hippocampal atrophy (hippocampal height and interuncal distance) and the severity of vascular pathology (number of brain infarcts). The distribution of lesions and a factor analysis showed that hippocampal atrophy is a better predictor of dementia than the number of brain infarcts. Multiple subcortical infarcts alone are probably not able to cause clinical dementia but the presence of vascular lesions increases the expression of concomitant Alzheimers disease.     

Diffusion MRI studies in vascular cognitive impairment and dementia

Since its introduction more than two decades ago, Magnetic Resonance Imaging (MRI) has not only allowed for visualization of the macrostructure of the CNS, but also has been able to study dynamic processes which constitute the substrate of currently available MRI variants. While conventional Diffusion Weighted Imaging (DWI) permits a robust visualization of lesions just a few minutes after the onset of cerebral ischemia, Diffusion Tensor Imaging (DTI) measures the magnitude and direction of diffusion, leading to the characterization of cerebral white matter (WM) microstructural integrity. In this paper, the potential role of MRI techniques, particularly DTI, for the study of the relationship between changes in the microstructural integrity of WM and cognitive impairment in the context of cerebrovascular disease are discussed. Significant correlations between scores of behavioral measures of cognitive function and regional anisotropy values are an example of the potential efficacy of DTI for in vivo studies of brain connectivity in vascular neurodegenerative conditions.     

Different responses to rivastigmine in subcortical vascular dementia and multi-infarct dementia

Vascular dementia (VaD) is associated with a large amount of heterogeneity, as it groups together a broad category of patients in whom various manifestations of cognitive decline are attributed to cerebrovascular or cardiovascular disease. Thus, a study was designed to determine the effects of rivastigmine on cognitive function, global daily living performance, and behavioral disorders in VaD patients versus an active control (nimodipine), stratifying patients according to the type of VaD, subcortical vascular dementia (sVAD), and multi-infarct dementia (MID). The trial was a prospective study. This study shows that long-term treatment with rivastigmine, at dosages approved for therapeutic use in Alzheimer's disease, produces significant improvement in all behavioral symptoms in 2 forms of VaD, MID and sVaD, except delusions. It also suggests that rivastigmine may enable a reduction in concomitant neuroleptics and benzodiazepines in VaD, especially in MID. The results are discussed with an overview of the literature.     

皮质下缺血性血管性痴呆患者认知功能与脑白质弥散张量成像的关系

目的探讨皮质下缺血性血管性痴呆(SIVD)患者认知功能与脑白质弥散张量成像(DTI)的关系。方法采用MMSE、蒙特利尔认知测评量表(Mo CA)及临床痴呆量表(CDR)评价60例SIVD患者(SIVD组)和45名正常对照者(正常对照组)。应用DTI技术测量患者脑白质不同感兴趣区(ROI)各向异性分数(FA)和表观弥散系数(ADC)。SIVD组用常规头颅MRI采用年龄相关白质改变(ARWMC)评分方法对侧脑室周围脑白质高信号严重程度进行评分。结果与SIVD组比较,正常对照组MMSE及Mo CA评分显著增高,CDR评分显著降低(均P0.01)。与正常对照组比较,SIVD组双侧额叶前部、双侧侧脑室前角区及后角区的FA值显著下降,ADC值显著升高(P0.05~0.01)。其余各区FA及ADC值差异无统计学意义。SIVD组ARWMC评分为1分11例(18.3%),2分31例(51.7%),3分18例(30.0%)。正常对照组中5人(11.1%)为1分。Spearman相关性分析显示,SIVD组ARWMC评分与双侧侧脑室前角区及后角区FA值呈负相关(r=-0.912,P0.01),与ADC值呈正相关(r=0.891,P0.01)。双侧额叶前部皮质下白质及海马区FA值与MMSE及Mo CA评分呈正相关(P0.05~0.01)。结论 SIVD患者多个ROI的FA值降低及ADC值的增高程度,可以反映认知功能障碍的程度。     

Default mode network integrity changes contribute to cognitive deficits in subcortical vascular cognitive impairment,no dementia

Brain Imaging and Behavior - Vascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that are insufficient to confirm a diagnosis...     

The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia

OBJECTIVE: Subcortical ischemic vascular lesions, which are closely related to small vessel disease, are a common substrate of cognitive impairment and dementia. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic variant of small vessel disease resulting from mutations in NOTCH3. Mutation carriers almost invariably develop cognitive deficits and eventually dementia. The current study describes the profile of cognitive abnormalities in CADASIL subjects. METHOD: A cross-sectional study of 65 mutation carriers (mean age=47.3 years, SD=10.5) and 30 matched comparison subjects (mean age=47.2 years, SD=14.0) was conducted. Participants underwent a series of assessments that included ratings of global cognition, the cognitive portion of the Vascular Dementia Assessment Scale, and specific tests of executive function and attention with measures of processing speed and error monitoring. RESULTS: CADASIL subjects had pronounced impairments of the timed measures (Stroop II and III, Trail Making Test, symbol digit, digit cancellation). Measures of error monitoring (Stroop III, Trail Making Test, symbol digit, maze task) were also significantly affected but to a lesser extent. Prominent deficits further included verbal fluency and ideational praxis. Recall, orientation, and receptive language skills were largely preserved. Subgroup analyses indicated a similar profile in subjects with early and advanced impairment of global cognitive performance. CONCLUSIONS: The findings highlight processing speed as the most substantial area of cognitive impairment in CADASIL subjects, with less pronounced yet significant deficits in other aspects of executive performance and attention. This profile of cognitive impairment is present at an early stage and enables the construction of targeted test batteries for clinical trials. It is hypothesized that the profile of dysfunction described here represents the core of the cognitive syndrome associated with small vessel disease and subcortical ischemic vascular lesions.     

Nimodipine in subcortical vascular dementia trial

Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.