Memory complaints with and without memory impairment: the impact of leukoaraiosis on cognition

White matter alterations, leukoaraiosis (LA) on structural MRI, are associated with cognitive deficits and increased risk of dementia. LA may also impact on subjective memory complaints in otherwise healthy older adults. Little is known about the interplay between LA memory complaints and cognition. We investigated cognitive phenotypes associated with LA in 42 non-demented older adults categorized as having subjective cognitive complaints with no objective cognitive impairment-the subjective cognitive impairment group (SCI; n = 12), amnesic mild cognitive impairment (aMCI; n = 20), or healthy controls (HC; n = 11). We measured LA severity on MRI with a 40-point visual rating scale. Controlling for age and Mini-Mental State Examination (MMSE) score, analyses revealed multiple between-group differences. Follow-up linear regression models investigating the underlying contributors to each clinic group's cognitive profile indicated that LA contributed to learning slope variance (after accounting for age and MMSE) but only for the SCI group. Although the SCI group showed a significantly steeper learning slope when compared to HC and aMCI, increasing LA severity negatively impacted this group's rate of learning. This, in conjunction with the significant contribution of age on SCI learning slope performance variance suggests that greater LA burden at a younger age may contribute to subtle changes in learning for individuals with subjective cognitive complaints.     

Pathomechanism of leukoaraiosis

Ischemic demyelination in the white matter of the brain is a frequent clinical entity. In neuroimaging terms, it is referred to as leukoaraiosis (LA). LA can reflect a broad public health problem, which is caused by a cognitive impairment ranging from mild slowness of thinking to full-blown subcortical dementia. One-quarter of subjects aged 65 yr or over are affected by some degree of white matter changes. There are a number of genetic factors that can be associated with circulatory disturbances of the white matter of the brain. A slight chronic hypoperfusion or an endothelial dysfunction associated with unfavorable genetic variations such as methylenete-trahydrofolate reductase C677T variation and angiotensin-converting enzyme I/D polymorphism then may lead indirectly to a malfunction of the molecular cross-talk between the nucleus and the mitochondria. This results in a decrease in the production of energy in the glia cells and thereby the beginning of demyelination. From another aspect, the presence of either the apolipoprotein E2 or 4 alleles may cause an increased vulnerability to a slight chronic hypoperfusion of the white matter by reducing the range of mechanical and chemical flexibility of the glial cytoskeleton. In consequence of the chronic hypoperfusion, the functionally damaged kinesin protein gives rise also to the disturbances of the trafficking of the myelin basic protein mRNAs in the oligoden-drocytes. On the basis of the current knowledge on LA, this article suggests a hypothetical molecular bridge between the genetic, biochemical, and clinical processes.     

Genetics of leukoaraiosis

Computed tomography and magnetic resonance imaging of the brains of elderly individuals frequently show areas of altered signal intensity in the periventricular and subcortical white matter, referred to as leukoaraiosis. Although mildly affected individuals appear asymptomatic, larger burdens of leukoaraiosis are associated with deficits of cognition and gait. Histopathologically, areas of leukoaraiosis invariably show sclerosis, luminal narrowing, and tortuosity of small arteries and arterioles, accompanied by variable degrees of gliosis, demyelination, and axonal loss resulting from ischemia. Genetic variation plays a substantial role in interindividual differences in the volume of leukoaraiosis and its associated adverse clinical outcomes. Characterizing genetic factors contributing to interindividual differences in leukoaraiosis has the potential to enhance understanding of molecular determinants of ischemic brain injury and lead to new approaches to the diagnosis, evaluation, treatment, and prevention of this common form of vascular dementia.     

Binswanger病、脑白质疏松症及其合并脑梗死患者的认知功能障碍

目的　探讨Binswanger病 (BD)、脑白质疏松症 (LA)及LA合并脑梗死 (LA +CI)患者的认知功能障碍程度及其临床意义。方法　采用简易精神状态量表 (MMSE)和临床记忆量表 (CMS)检查BD(33例 )、LA(2 7例 )、LA +CI(31例 )患者及健康对照者 (30名 )的认知功能状态 ,并比较其障碍的程度。结果　 (1)BD组、LA组、LA +CI组MMSE及CMS评分均明显低于对照组 (P <0 0 5～ 0 0 1)。 (2 )BD组、LA +CI组MMSE及CMS评分均明显低于LA组 (P <0 0 5～ 0 0 1)。 (3)LA组轻度认知功能障碍 2 1例 (77 8% ) ;BD组中度认知功能障碍 8例 (2 4 2 % ) ,痴呆 2 5例 (75 .8% ) ;LA +CI组中度认知功能障碍 6例 (19 4 % ) ,痴呆 2 4例 (77 4 % )。结论LA大多有轻度认知功能障碍 ,而BD和LA +CI多为中度认知功能障碍和痴呆。认知功能障碍的程度是临床诊断BD、LA的参考指标。     

Progression from normal cognition to mild cognitive impairment in a diverse clinic-based and community-based elderly cohort

Introduction

Investigation of the conversion rates from normal cognition (NC) to mild cognitive impairment (MCI) is important, as effective early intervention could potentially prevent or substantially delay the onset of dementia. However, reported conversion rates differ across studies and recruitment source. Our study examined predictors of conversion from NC to MCI in a racially and ethnically diverse sample drawn both from community and clinic recruitment sources.

脑白质疏松与脑微出血的相关性研究

目的 探讨脑白质疏松(LA)与脑微出血(CMBs)这两种脑小血管病的相关性. 方法 选择自2009年6月至2010年1月南方医院神经内科收治的68例、汕头市中心医院神经内科收治的45例患者为研究对象(共113例),均诊断为脑小血管病,均行头颅MRI扫描(T1WI、T2WI、FLAIR及SWI成像)、相关血生化检查及基本资料收集[包括性别、年龄、吸烟史、饮酒史、高血压、糖尿病、胆固醇(CHOL)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、纤维蛋白原(FIB)].根据MRI结果将LA分为侧脑室周围LA 0～3级和皮质下LA 0～3级,计算CMBs病灶数量并分为0～3级. 结果 伴有CMBs的LA患者年龄、糖尿病史、腔隙性脑梗死、血糖值、HDL与不伴有CMBs的LA患者比较,差异均有统计学意义(P＜0.05).CMBs分级在不同级别侧脑室周围LA患者和不同级别皮质下LA患者中的分布比较差异均有统计学意义(P＜0.05).有无CMBs与有无LA之间、CMBs分级与侧脑室周围LA分级之间、CMBs分级与皮质下LA分级之间均存在相关性(rs=0.439,P=0.000;rs=0.506,P=0.000;rs=0.448,P=0.000). 结论 患者年龄越大,患糖尿病、腔隙性脑梗死、高血糖、低HDL时更容易患LA及CMBs.CMBs、LA两种疾病互为危险因素,其严重程度呈正相关,并共同受心血管危险因素影响.     

Association of platelet hyper-aggregability with leukoaraiosis

OBJECTIVES: To investigate whether there is any relationship between leukoaraiosis and platelet hyper-aggregability of the systemic blood. METHODS: Platelet aggregability, leukoaraiosis, hypertension and hematocrit were assessed in 175 consecutive out-patients attending a regular clinic. Platelet aggregability was estimated by an optical analytical method using two different concentrations each of ADP and collagen (the double ADP method). Hyper-aggregability and non hyper-aggregability were defined with this method. RESULTS: Patients with leukoaraiosis (73 cases) showed a significantly higher incidence of platelet hyper-aggregability than patients with no leukoaraiosis (102 cases) (90.4 vs 56.9%, P=0.000001). Leukoaraiosis was also significantly related to age. Hypertension was a less significant risk factor (P=0.023). CONCLUSIONS: Platelet hyper-aggregability is a significant feature in leukoaraiosis, and appears to be a more important risk factor than hypertension. Normalization of platelet hyper-aggregability might offer an alternative strategy for the prevention of leukoaraiosis in patients with platelet hyper-aggregability, although an interventional study is essential.     

血浆黏度与脑白质疏松的相关性研究

目的探讨血浆黏度与脑白质疏松(LA)之间的相关性。方法选取正常对照组60例和LA组60例,收集2组的临床资料来评估LA相关可能的危险因素,进一步对血浆黏度进行多因素Logistic回归分析,并采用MRI的Fazekas方法对LA组进行分级,评估不同程度LA患者的血浆黏度水平差异。结果 LA组的年龄、三酰甘油及血浆黏度水平与对照组比较,差异有统计学意义(P<0.05),血浆黏度的增高与LA的发生相关(OR=1.298),当调整其他危险因素后,差异仍有统计学意义(P<0.05);且随着Fazekas评分增加,血浆黏度水平随之增加。结论血浆黏度水平和LA相关,可能是LA的独立危险因素,且随着LA程度的加重而增高。     

Risk factors and leukoaraiosis in stroke patients

Objectives – Although leukoaraosis (LA) is a common CT finding, its pathogenesis remains debated: if small-artery pathology may explain in some cases white matter changes, many other factors, such as hemodynamic perturbations, might also lead to LA. To test these hypothesis, we determined the types of cerebrovascular risk factors associated with leukoaraosis in consecutive patients with acute cerebrovascular event. Patients and methods – Using CT-scans, we prospectively studied in 610 patients consecutively admitted for an acute cerebral event, the relation between LA and the following cerebrovascular risk factors: age, sex, arterial hypertension, diabetes mellitus, hyperlipemia, alcohol consumption, birth contraceptive pills, previous transient ischemic attack or stroke, migraine, atrial fibrillation, valvulopathy, coronaropathy, left ventricular hypertrophy, stenosis of the internal carotid artery, by means of a multiple linear regression. Relation with cerebral atrophy was also evaluated. Results – We found LA scores to depend on increasing age (p=0.0001), female sex (p=0.0146), history of stroke or TIA (p=0.0051), history or current atrial fibrillation (p=0.0083), increasing cerebral atrophy score (p=0.0001), absence of hyperlipemia (p=0.0003) and absence of alcohol consumption higher than 300 g/week (p=0.0398). Conclusion – Our findings do not support the hypothesis that, in stroke patients, LA share similar risk factors than small-vessel disease; other cerebrovascular risk factors may also contribute to LA, perhaps because of decreased cerebral blood flow.     

Reduced noncovalent connections in leukoaraiosis

Leukoaraiosis is manifested as diffuse areas of hypodensity on CT scans and as hyperintensity signals on T2-weighted MRI scans. This neuroimaging phenomenon is frequently associated with cognitive decline in the middle-aged or elderly. Ischemic demyelinization or chronic perivascular toxic edema in the white matter of the brain is presumed to be behind this entity. Genetic and environmental factors together lead to the development of leukoaraiosis. The possibility of hypoxia-induced cytoskeleton damage was suggested by recent experimental genetic data. This article discusses the chemical and biochemical consequences of this possibility. It suggests a new approach to leukoaraiosis by linking genetic data, medicinal chemistry, system theory and histopathological data. In accordance with this chemical model, a synchronously evolving slight intracellular ATP depletion along the glial cytoplasm may lead to an unstable biochemical condition in glial cells, which finally predisposes to leukoaraiosis.     

脑白质疏松症的临床危险因素分析

目的探讨脑白质疏松症的临床危险因素。方法回顾性分析2015-01-01—2016-06-01连续收治的116例脑白质疏松症患者的临床资料,利用脑白质疏松症Fazekasz量表评分将LA患者分为中度组(n=70)和重度组(n=46),并对其临床资料进行统计学处理。结果脑白质疏松症合并高血压史85例(73.2%),糖尿病15例(12.9%),脂代谢异常76例(65.5%),大动脉粥样硬化63例(54.3%),平均同型半胱氨酸水平为21.98mg/L。与中度组相比,重度组年龄较大,胆固醇、低密度脂蛋白、载脂蛋白A及载脂蛋白B的水平更低(P0.05);而同型半胱氨酸水平更高(P0.05)。结论年龄、高血压、脂代谢异常、同型半胱氨酸水平等因素均与LA的发生有关;其中高龄和高同型半胱氨酸与LA的发生有关,而血胆固醇、低密度脂蛋白及载脂蛋白A、B为LA的保护因素,其降低与更高的Fazekasz量表评分有关。     

白质疏松与脑梗死后意识状态的关系

目的探讨白质疏松与脑梗死后意识状态的关系。方法采用Glasgow昏迷量表评分追踪观察了138例脑梗死患者,白质疏松组78例,非白质疏松组60例。结果白质疏松(OR=5.294,95%CI=1.451-19.318)和OCSP分型(OR=14.489,95%CI=4.121-50.934)是影响意识障碍的独立危险因素。在发病初白质疏松组的意识障碍重于非白质疏松组,在发病1m和3m时,白质疏松组患者意识障碍的改善程度明显小于非白质疏松组。结论白质疏松在梗死早期加重意识障碍并影响意识的恢复。