Impact of White Matter Lesions on Depression in the Patients with Alzheimer's Disease

Objective

Comorbid depression is common in patients with Alzheimer''s disease (AD). An increase in white matter lesions (WMLs) has been associated with depression in both elderly individuals with normal cognition and patients with Alzheimer''s disease. We investigated whether the severity and location of WMLs influence the association between WMLs and comorbid depression in AD.

Methods

We enrolled 93 AD patients from Seoul National University Bundang Hospital. We administered both the Mini International Neuropsychiatric Inventory (MINI) and the Korean version of the Consortium to Establish a Registry for Alzheimer''s Disease Assessment Packet (CERAD-K) clinical and neuropsychological battery. Subjects also underwent brain magnetic resonance imaging (MRI). We diagnosed AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer''s Disease and Related Disorders Association. We diagnosed depressive disorders according to the DSM-IV diagnostic criteria, and evaluated the severity of depressive symptoms using the Korean version of the Geriatric Depression Scale (GDS-K). We quantified the WML volumes from the brain MRI using a fully automated segmentation algorithm.

Results

The log of the WML volume in the frontal lobe was significantly associated with depressive disorders (odds ratio=1.905, 95% CI=1.027-3.533, p=0.041), but not with the severity of depressive symptoms as measured by the GDS-K.

Conclusion

The WML volume in the frontal lobe conferred a risk of comorbid depressive disorders in AD, which implies that comorbid depression in AD may be attributed to vascular causes.     

H型高血压患者脑白质病变和脑血流动力学的特点

目的 探讨H型高血压患者脑白质病变（white matter lesions,WML）和脑血流动力学的特点。 方法 回顾性纳入连云港市第二人民医院神经内科住院的WML伴高血压患者,根据Hcy水平,分成 H型高血压组和单纯高血压组。所有患者行MRI检查并采用Fazekas量表评估WML严重程度,TCD检测 颅内动脉并分析其搏动指数（pulsatility index,PI）、平均血流速度（mean blood flow velocity,Vm）等血 流动力学特点。对比分析两组患者WML严重程度和脑血流动力学特点。以正常PI值（0.65～1.10）为界, 将研究对象分为PI正常组与增高组（＞1.10）,采用Logistic回归分析其影响因素。 结果 最终入组217例WML伴高血压患者,年龄40～85岁,平均66.35±8.08岁,男性150例（69.1%）。 其中H型高血压组患者131例（60.4%）。H型高血压组总体脑白质Fazekas评分高于单纯高血压组 （2.45±0.33 vs 2.16±0.36分,P =0.011）;脑室旁Fazekas评分也高于单纯高血压组（1.48±0.12 vs 1.38±0.15分,P =0.009）;两组患者深部白质Faze kas评分差异无统计学意义。H型高血压组大 脑中动脉PI值（1.21±0.20 vs 1.10±0.17,P =0.016）和大脑前动脉PI值（1.16±0.18 vs 1.07±0.18, P =0.023）均高于单纯高血压组。Logistic回归分析显示,H型高血压是大脑中动脉PI值（OR 2.080, 95%CI 1.073～4.033,P =0.030）、大脑前动脉PI 值（OR 1.951,95%CI 1.015～3.749,P =0.045）的独立 影响因素。 结论 H型高血压与WML的严重程度有关,是大脑中动脉、大脑前动脉PI值的独立影响因素。     

脑小血管病脑白质损伤动物模型

脑小血管病是导致认知功能减退、步态情感障碍和痴呆的重要脑血管疾病,脑白质弥漫 性损伤是该病的重要影像学特征。结合国内外近年来相关研究内容,本文对不同的脑小血管病白质 损伤动物模型制作进行了系统性回顾,包括单一型动物模型如双侧颈总动脉狭窄模型、脑淀粉样血 管病模型、Notch3 转基因小鼠模型、自发性高血压大鼠模型、易卒中型肾血管性高血压大鼠模型,以 及由两个或两个以上单一型动物模型组合而成的复合型动物模型等。     

脑微出血与脑白质病变及腔隙性梗死关系研究

目的 探讨脑微出血（cerebral microbleeds,CMBs）与脑白质病变（white matter lesions,WML）及腔隙性 梗死（lacunar infarcts,LI）的关系。 方法 连续纳入2010年2月至2012年2月解放军总医院南楼神经内科病房根据病史及头颅影像学检 查确诊患有脑血管病或具有高血压、糖尿病、高脂血症等脑血管病危险因素者217例。采用GE公司 1.5T磁共振成像行头颅常规序列及T2 *血管加权成像（T2 star weighted angiography,SWAN）序列扫 描。记录深部及皮层部位CMBs病灶数,按照Fazekas评分和Scheltens改良量表将脑室旁白质高信号 （peri-ventricular hyperintensities,PVH）和深部白质高信号（deep white m atter hyperintensities,DWMH） 分别评分,根据病灶数量评估LI的严重程度分析CMBs与PVH、DWMH及LI的关系。 结果 随着PVH和DWMH评分的升高,CMBs的检出率分别由41.8%（PVH=1）及40.8%（DWMH=1）升高 至68.8%（PVH=3）及76.9%（DWMH=3）;随着LI数量的增加,CMBs的检出率由46.3%升高至75%。深 部CMBs与PVH及DWMH的严重程度有较强相关性（rs =0.345,P＜0.001;rs =0.346,P＜0.001）,与LI 亦显 著相关（r s =0.281,P＜0.001）;而皮层CMBs与PVH及DWMH严重程度仅呈弱相关（r s =0.219,P =0.001; rs =0.189,P =0.005）,与LI无显著相关性。 结论 深部CMBs与脑室旁及深部脑白质病变、LI相关。     

急性缺血性卒中患者血尿酸水平与脑白质病变的相关性研究

目的 探讨急性缺血性卒中患者血尿酸水平与脑白质病变（white matter lesions,WMLs）的相关性。 方法 连续入选2011年1月～2012年12月发病48 h内的首发缺血性卒中患者进行横断面研究,按 照Ylikoski评分将患者分为两组：重度WMLs组、无或轻度WMLs组。比较两组患者血糖、甘油三酯 （triglyceride,TG）、总胆固醇（total cholesterol,TC）、低密度脂蛋白-胆固醇（low density lipoproteincholesterol, LDL-C）、高密度脂蛋白-胆固醇（high density lipoprotein-cholesterol,HDL-C）及血尿酸水 平,并行Logistic回归分析重度WMLs危险因素。 结果 共入选急性缺血性卒中患者321例,其中重度WMLs组159例,无或轻度WMLs组162例。重度 WMLs组患者年龄（P＜0.001）、糖尿病发生率（P =0.011）、血糖（P＜0.001）、血尿酸水平（P＜0.001）、 高尿酸血症发生率（P =0.002）均高于无或轻度WMLs组（P均＜0.05）,两组性别、高血压发生率、收 缩压、舒张压、心房颤动发生率、血TG、TC、LDL-C、HDL-C水平、吸烟史比例无显著差异。校正年 龄、性别、血压、伴发高血压、糖尿病、心房颤动、血糖、血脂及吸烟史后,年龄［比值比（odds ratio, OR）1.062,95%可信区间（confidence interval,CI）1.0008～1.119,P =0.023］、血尿酸水平（OR 1.531, 95%CI 1.186～1.975,P =0.001）和高尿酸血症（OR 1.131,95%CI 1.047～1.222,P =0.002）是急性缺血 性卒中患者发生重度WMLs的独立危险因素。 结论 血尿酸水平和高尿酸血症是急性缺血性卒中患者伴发重度WMLs的独立危险因素     

White Matter Changes in Depression and Alzheimer's Disease: A Review of Magnetic Resonance Imaging Studies

This article reviews magnetic resonance imaging (MRI) studies of white matter lesions in depression and Alzheimer's disease. Although conflicting reports exist, many studies show that white matter lesions are more prevalent in both conditions, with depression associated with deep white matter lesions (DWML) and Alzheimer's disease with periventricular lesions (PVL). In normal ageing and depression there is some evidence that such lesions may be associated with neuropsychological dysfunction, though the relationship is less clear for Alzheimer's disease. One difficulty in drawing firm conclusions from work so far is that confounding variables, such as cerebrovascular risk factors, have now always been taken into account. Most studies have been cross-sectional so there is little information regarding the progression, prognostic significance and pathogenesis of such lesions. These issues merit examination in longitudinal studies combining serial MRI with clinical assessments of subjects who have been fully assessed for vascular risk factors.     

脑白质病变患者认知功能的前瞻性研究

目的 探讨不同部位和严重程度脑白质病变（white matter lesions,WMLs）患者的认知功能损害特点。 方法 前瞻性纳入179例WMLs病例和97例磁共振成像（magnetic resonance imaging,MRI）正常对照组, 并收集人口学资料,对WMLs的严重程度进行Fazekas视觉等级评分,依据WMLs病变部位分为皮质下脑 白质病变（subcortical white matter lesions,SWML）组、脑室旁脑白质病变（periventricular lesions,PVL）组 和混合组,采用蒙特利尔认知评估量表（Montreal Cognitive Assessment Scale,MoCA）分析不同部位和 严重程度WMLs的认知功能差异。根据MoCA将WMLs组分为WMLs认知损害亚组（116例）及WMLs认知正 常亚组（63例）,分析探讨WMLs患者认知损害的危险因素。 结果 与正常组比,WMLs组在MoCA总分（P ﹤0.001）、视空间与执行能力（P ﹤0.001）、命名（P =0.019）、 语言（P =0.005）、抽象理解（P =0.003）、延迟记忆（P ﹤0.001）方面显著性减低。Fazekas分级越高, MoCA总分及各项评分显著减低（P均﹤0.05）。PVL组、SWML组和混合组与对照组相比,在MoCA总分（P 均﹤0.001）、视空间与执行能力（P 均﹤0.001）、语言（P =0.006,0.022,0.008）、抽象理解（P =0.003, 0.011,0.016）及延迟记忆（P均﹤0.001）上差异有统计学意义。WMLs亚组分析显示高教育程度是WMLs发 生认知损害的保护因素。 结论 高教育程度是WMLs患者认知损害的保护因素。WMLs患者在视空间与执行功能、延迟回忆方面 存在明显的认知损害。WMLs病变程度越严重,认知功能下降越显著。皮质下WMLs、脑室旁WMLs及混 合组均在视空间与执行能力、语言、抽象理解、延迟记忆方面损害严重。     

脑小血管病脑白质高信号与认知障碍的关系研究进展

脑小血管病（cerebral small vessel disease,CSVD）是临床上常见的一类与年龄相关的脑血管 疾病。脑白质高信号（white matter hypertensities,WMH）是CSVD的影像标志物之一。WMH患病率极高, 与认知障碍的发生发展密切相关,但其影像表现及临床症状的异质性为早期发现、早期诊断带来了 困难。本文从病理学、影像学及生物学3方面对WMH发生发展及其导致认知障碍的机制研究现况进 行综述,同时总结目前的治疗策略,提出了接下来的研究目标及方向：能够反映预后的标志物及预测 模型的研究,WMH发生发展的病理生理学机制研究,针对早期干预、药物开发的潜在靶点的研究等。     

小血管病性脑白质病变与认知功能障碍关系研究

目的 评估小血管病患者脑白质病变程度与认知功能的相关性。 方法 通过对浙江大学医学院附属第一医院神经内科门诊患者进行老年人认知功能下降知情者问 卷（informant questionnaire on cognitive decline in the elderly,IQCODE）、简易智能状态检查量表（minimental state examination,MMSE）、临床痴呆评定量表（clinical dementia rating,CDR）评分以及相关认 知功能评估,结合头颅磁共振成像（magnatic resonance imaging,MRI）检查及临床资料,筛选小血管病 变患者,并通过相关统计分析计算不同部位脑白质病变的程度及其对认知功能的影响。 结果 本研究共纳入患者147例,其中小血管病变（cerebral small vessel disease,SVD）患者33例,SVD患 者记忆力（z =-3.36）、定向力（z＝-3.14）、处理判断力（z =-3.38）以及社会事物能力（z =-3.22）较 正常者都明显下降（P =0.00）。脑室周围病变与MMSE分数（r =0.82）、CDR总分（r =0.62）、CDR记忆分 （r =0.82）显著相关（P值均=0.00）,皮质下病变与MMSE分数（r =0.51,P =0.01）、CDR记忆分（r =0.49, P =0.02）中度相关。 结论 在脑小血管病患者,MMSE评分、CDR评分对于脑白质病变特别是脑室旁病变的进展可能具有 一定的预测价值。     

沙漠化地区缺血性脱髓鞘性脑白质病变危险因素研究

目的 回顾性研究武威市沙漠化地区缺血性脱髓鞘性脑白质病变的危险因素,为临床中预防沙漠地 区缺血性脱髓鞘性脑白质病变的发生提供理论依据。 方法 收集武威市人民医院神经内科2011年1月-2015年12月住院或门诊筛查出的缺血性脑血管病变 患者共500例。按不同居住地、不同危险因素对所筛选病例进行分析。采用多因素Logistic回归分析缺 血性脱髓鞘性脑白质病变患者的相关危险因素。 结果 沙漠组的缺血性脱髓鞘性脑白质病变发生率为62.4%,平原组的缺血性脱髓鞘性脑白质病变 发生率为49.6%;沙漠组中脑白质病变中重度病变占22.4%,平原组的脑白质病变中重度病变占8.4%。 多因素分析结果表示沙漠化天气、吸烟、饮酒、糖尿病、高血压、脂代谢异常、颈动脉硬化、高同型半 胱氨酸是加重缺血性脑白质病变的危险因素。 结论 沙漠化地区缺血性脱髓鞘脑白质病变的发生率较平原地区偏高,以重度病变为主。     

Wilson's Disease with Extensive Degeneration of Cerebral White Matter and Cortex

Abstract: This is a report of an autopsy case of Wilson's disease with widespread degeneration of the cerebral cortex and white matter, the basal ganglia and thalamus and, to a lesser degree, the cerebellum and brain stem. The patient was a 28-year-old man at the time of death with the clinical course of a 20-year duration.
The lesions consisted of spongy degeneration leading to a cavity formation with insufficient glia fiber proliferation. We noted the characteristic findings of Alzheimer glia (Types I and II) and Opalski cells and the new formation in capillaries.
The distribution of the changes in the hemispheres showed the typical pattern with a tendency of preferential superior and anterior localization and a relative preservation of the hippocampal formation, carcarine areas, amygdaloid nuclei and the hypothalamus.
Similar cases in the literature were reviewed.     

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

Background

Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD).

Objective

The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively.

Methods

Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses.

Results

Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores.

Conclusions

We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

White matter tract alterations in Parkinson's disease patients with punding

ObjectiveTo assess brain white matter tract alterations in patients with Parkinson's disease and punding (PD-punding) compared with controls and PD cases without any impulsive-compulsive behaviour.MethodsForty-nine PD patients (21 PD-punding and 28 PD with no impulsive-compulsive behaviours) and 28 controls were consecutively recruited. Clinical, cognitive and psychopathological evaluations were performed. Diffusion tensor MRI metrics of the main white matter tracts were assessed using a tractography approach.ResultsCompared with controls, both PD groups showed white matter microstructural alterations of the left pedunculopontine tract and splenium of the corpus callosum. PD-punding patients showed a further damage to the right pedunculopontine tract and uncinate fasciculus, genu of the corpus callosum, and left parahippocampal tract relative to controls. When adjusting for depression and/or apathy severity, a greater damage of the genu of the corpus callosum and the left pedunculopontine tract was found in PD-punding compared with patients with no impulsive-compulsive behaviours.ConclusionsPD-punding is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices. These alterations are at least partially independent of their psychopathological changes. Diffusion tensor MRI is a powerful tool for understanding the neural substrates underlying punding in PD.     

脑大动脉病变与脑白质高信号的相关性研究进展

脑大、小血管共同构成了脑的血管树,它们在结构和功能上有一定的相关性。近年来,脑 大血管病变与脑小血管病之间相关关系的研究逐渐受到重视。大动脉粥样硬化、动脉延长扩张及管 壁僵硬度增大从不同侧面反映了大血管病变的特点,脑白质高信号是脑小血管病重要的影像学表现。 本文对动脉粥样硬化、动脉延长扩张及僵硬度增大与脑白质高信号之间的相关性进行综述,以探讨 脑大血管病变与脑小血管病的关系。