脑小血管病患者步态障碍的脑结构改变研究进展

步态障碍是脑小血管病(CSVD)的重要皮质下损害特征,显著增加跌倒风险,其发病机制目前尚不明确。在CSVD传统影像学特征中,脑白质高信号(WMH)与步态障碍最为相关,且以脑室旁白质高信号(PWMH)和幕下WMH为著;WMH严重程度与步态障碍可能是一种阈值关系,即仅重度WMH影响步态活动。在GMV及CTh方面,CSVD患者全脑灰质体积减少和皮质变薄均与步态障碍密切相关。弥散张量成像(DTI)研究发现CSVD步态障碍患者存在着包括高级认知控制和下行运动纤维束在内的广泛白质微结构受损,且不同的白质纤维结构可能与不同的步态损害特征有关。该文分别从传统影像学表现、灰质体积(GMV)、皮质厚度(CTh)及脑白质微结构等方面综述CSVD步态障碍在脑结构方面取得的研究进展。该文分别从传统影像学表现、灰质体积(GMV)、皮质厚度(CTh)及脑白质微结构等方面综述CSVD步态障碍在脑结构方面取得的研究进展,这有利于进一步提高对CSVD步态障碍神经机制的认识。     

白质高信号与脑小血管病卒中后早期认知损害的关联

目的:白质高信号(white matter hyperintensity,WMH)是脑小血管病(cerebral small vessel disease,CSVD)的重要影像学特征。本研究应用数据驱动法对WMH进行定量分析,与传统的半定量评定方法进行比较,旨在探讨WMH与CSVD(脑卒中后)早期认知损害的相关性。方法:2015年7月—2018年2月上海交通大学医学院附属仁济医院脑卒中专病门诊连续登记的117例CSVD患者符合病例选择标准,其中72例为轻度认知损害(mild cognitive impairment,MCI)患者,45例为无认知损害(no cognitive impairment,NCI)患者。2组患者的基线人口社会学和血管危险因素的差异无统计学意义(P 0.05)。对所有患者进行神经心理学检查,并进行多模态磁共振成像检查,采用Fazekas量表对WMH进行半定量评分,并对WMH体积进行定量计算。比较2组患者的认知功能,并对WMH半定量评分和WMH体积定量计分与认知功能进行相关性分析。结果:MCI与NCI患者的认知功能(注意-执行、视空间、语言和记忆功能)差异均有统计学意义(P 0.05),WMH半定量Fazekas评分的差异无统计学意义(P=0.090),而WMH体积定量计分差异有统计学意义(P=0.004)。在校正年龄、性别和受教育年限后,WMH半定量Fazekas评分与认知功能均无相关性(P 0.05),而WMH体积定量计分与认知功能均有显著相关性(P 0.05)。深部WMH体积主要与注意-执行(P 0.05)和视空间功能(P 0.05)显著相关,而侧脑室旁WMH体积与认知功能均显著相关(P 0.05)。结论:WMH与CSVD患者认知功能下降密切相关。WMH体积定量计分较WMH半定量Fazekas评分能够更敏感地评估CSVD患者早期认知功能的变化,且不同部位WMH与认知功能的相关性存在异质性。     

皮质下血管性认知障碍患者弥散张量成像和脑血流量的研究

目的明确脑小血管病(cerebral small vessel disease,CSVD)患者白质完整性、脑血流量及其认知障碍之间的关系。方法连续招募严格定义的CSVD患者58例,分为无认知障碍(no cognitive impairment,NCI)11例、血管性轻度认知障碍(vascular mild cognitive impairment,VaMCI)29例和血管性痴呆(vascular dementia,VaD)18例三组,评定脑室旁(periventricular,PV)及放射冠(corona radiate,CR)白质的弥散张量成像(diffusion tensor imaging,DTI)参数,即平均弥散率(mean diffusivity,MD)和各向异性分数(fractional anisotropy,FA)。应用CT灌注(CT perfusion,CTP)成像对PV和CR区进行脑血流量(cerebral blood flow,CBF)测定。对DTI参数、CBF和认知评分进行相关性分析。结果 1三组间PV区的CBF及MD值比较,差异均有显著性(P0.01),其中MD值与CBF以及注意执行功能间均呈显著相关性(P0.01),但CBF和认知功能间未见相关性。三组间FA值比较,差异均无显著性,FA值亦未显示与CBF以及认知功能的相关性。2三组间CR区的CBF和MD、FA值比较,差异均无显著性,仅CR区MD和注意执行功能有一定相关性(P0.05),CBF与DTI参数以及认知功能间均未见相关性。结论脑室旁白质完整性的破坏是CSVD患者认知损害的重要影像学标志,且与低灌注密切相关。     

脑小血管病非痴呆患者脑微出血与认知功能相关性研究

目的探讨脑小血管病非痴呆患者脑微出血(CMBs)数量、部位与认知功能损害的相关性。方法收集82例脑小血管病非痴呆伴有CMBs患者的临床资料,行头部MRI及磁敏感加权成像(SWI)检查,记录CMBs部位、数量,并完成MMSE和蒙特利尔认知评估量表(Mo CA)评分。结果 CMBs好发部位是基底节、颞叶及额叶;CMBs数量与Mo CA总分呈负相关(r=-0.293,P=0.014)有关,尤其在注意集中、延迟记忆(r=-0.266,P=0.026;r=-0.237,P=0.048)。额叶CMBs与视结构执行技能呈负相关(r=-0.240,P=0.03)。枕叶CMBs与语言、定向呈负相关(r=-0.218,P=0.049;r=-0.242,P=0.028)。岛叶和基底节区域CMBs与注意集中呈负相关(r=-0.236,P=0.033;r=-0.248,P=0.024)。DPWM区域CMBs与Mo CA总分、注意集中、记忆、语言呈现负相关(r=-0.269,P=0.015;r=-0.219,P=0.048;r=-0.240,P=0.030;r=-0.295,P=0.007)。结论 CMBs作为CSVD的标志物之一,在认知、早期诊断及病程发展中扮演着重要作用。     

症状性小动脉硬化脑小血管病患者脑微出血的危险因素分析

目的 应用头颅MRI 的SWI序列检测症状性小动脉硬化脑小血管病（cerebral small vessel disease,CSVD）患者脑微出血（cerebral microbleeds,CMBs）灶,分析不同部位CMBs的临床特征差异及CMBs的危险因素。方法 回顾性纳入2017年3月—2018年10月就诊于新疆昌吉州中医院神经内科的小动脉硬化的CSVD患者。根据有无微出血分为CMBs组与无CMBs组。应用二元logistic回归分析CMBs的独立危险因素;判断CMBs数量分级与独立危险因素的相关性。根据CMBs的位置分为脑叶区亚组、深部区亚组、幕下区亚组。比较脑叶区CMBs与非脑叶区CMBs、深部CMBs与非深部CMBs、幕下区CMBs与非幕下区CMBs亚组之间的临床特征差异。 结果 共纳入144例CSVD患者,CMBs组42例（29.2%）,无CMBs组102例（70.8%）,其中脑叶区18例,深部白质区23例,幕下区9例。二元logistic回归分析显示,低载脂蛋白b水平（OR 0.308,95%CI 0.099～0.957,P=0.042）及高空腹血糖值（OR 1.128,95%CI 1.015～1.254,P=0.026）、舒张压、脑梗死灶及假定血管源性腔隙灶是CMBs的独立危险因素。CMBs分级与载脂蛋白b呈负相关（r=-0.212,P=0.011）,与脑梗死灶分级（r=0.378,P＜0.001）、假定血管源性腔隙灶分级（r=0.411,P＜0.001）呈正相关。脑叶区CMBs与非脑叶区CMBs相比：脑叶区CMBs组BMI（24.4 kg/m2 vs. 23.5 kg/m2,P=0.045）、射血分数（61.0% vs. 60.0%,P=0.012）高于非脑叶CMBs组,心率（75.0次/分 vs. 83.0次/分,P=0.017）低于非脑叶CMBs组,文化程度分布组间差异有统计学意义（P=0.004）。深部CMBs组的男性比例（78.3% vs. 47.4%,P=0.038）高于非深部CMBs组,梗死灶（P=0.002）数量多于非深部CMBs组。结论 低载脂蛋白b水平及高空腹血糖值、舒张压、脑梗死灶及假定血管源性的腔隙灶是CMBs独立危险因素;CMBs分级与载脂蛋白b呈负相关,与脑梗死灶分级、假定血管源性腔隙灶分级呈正相关;BMI、射血分数、心率、文化程度与脑叶CMBs相关,性别、梗死灶分级与深部CMBs相关。     

基于智能分割分析脑小血管病患者白质高信号与认知功能的相关性研究

目的建立智能白质高信号(WMH)分割算法,分析脑小血管病(CSVD)患者WMH总体积和不同脑区WMH体积,并探讨其与认知功能的相关性。方法建立智能WMH分割算法,对CSVD患者头颅MRI显示的WMH分别进行智能WMH分割算法及人工勾画方法分析。采用Dice相似系数比较两种方案的一致性。采用神经心理量表多维度联合评估患者的认知功能,分析不同脑区WMH体积与认知功能的相关性。结果共纳入249例CSVD患者。建立智能影像系统并验证:智能算法分割WMH总体积与人工勾画方法比较具有显著相关性(r=0.896,P0.000 1);66.7%的脑区(26/39例)智能WMH体积与人工勾画比较具有显著相关性(均r0.5,P0.001),提示两种方法具有良好一致性。相关性分析提示:智能算法WMH总体积与简明精神状态量表、连线测试、数字符号测试、数字广度测试得分呈负相关(P0.05);白质分区中放射冠、内囊前肢、扣带回与Stroop色词和连线量表测试得分呈负相关(P0.05);放射冠、内囊前肢、丘脑辐射与数字广度测试得分呈负相关(P0.05)。结论智能WMH分割算法与人工勾画方法结果比较具有良好一致性;CSVD患者的WMH总体积与执行功能和注意力相关,白质分区中放射冠、内囊前肢、扣带回与执行功能相关,放射冠、内囊前肢、丘脑辐射与注意力相关。     

脑小血管病

目的探讨伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)患者脑微出血(cerebral microbleeds,CMBs)的分布特征及临床意义。方法回顾性纳入2017年6月-2019年12月北京协和医院基因确诊的连续CADASIL患者21例(CADASIL组),以及性别匹配的高血压动脉硬化性脑小血管病患者21例(高血压脑小血管病组)。所有患者均行头MRI检查(含T2^*/SWI序列),盲法读片并记录CMBs的数量和部位,分析两组CMBs分布的差异。结果CADASIL组年龄和常见血管病危险因素比例均低于高血压脑小血管病组。CADASIL组47.6%患者检出CMBs(共计115个),而高血压脑小血管病组高达95.2%(共计218个)。CADASIL组CMBs分布以丘脑最常受累(45.2%),其次是脑叶(皮层/皮层下,35.7%)、基底节(11.3%)。高血压脑小血管病组则以丘脑以外的基底节CMBs最多见(35.3%),其次是脑叶(26.6%)、丘脑(19.2%)、脑干(16.1%)。CADASIL患者丘脑CMBs/总CMBs比例、丘脑CMBs/(基底节CMBs+脑干CMBs)比例均高于高血压脑小血管病组(均P<0.001)。结论CADASIL患者CMBs分布以丘脑最常见,其次是皮层/皮层下区域,而高血压脑小血管病患者则以丘脑以外的基底节、脑干更常见。     

血管性认知障碍的早期预警因子

血管性认知障碍是指脑血管病及其危险因素引起的从轻度认知损害到痴呆的一类综合征。目前的研究认为,包括腔隙性脑梗死(LI)、白质高信号(WMH)、脑微出血(CMBs)、扩大的血管周围间隙(EPVS)等在内的脑小血管病(CSVD)、脑组织N-乙酰天门冬氨酸(NAA)/肌酸(Cr)比值降低、全脑血流灌注减少、动脉粥样硬化和动脉僵硬化、颈动脉狭窄、颅内动脉搏动指数增高、颅内血管对高/低碳酸血症的反应性降低、自发性微栓子、血清高血同型半胱氨酸,以及低TT3、脑脊液高α1-抗胰凝乳蛋白酶、YKL-40和NF-L等分子标志物均可作为血管性认知障碍的早期预警因子。磁共振和超声技术的应用为这些早期预警因子的检出提供了有力帮助。     

老年脑小血管病影像学总负担评分与认知功能障碍的相关性分析

目的研究老年人群脑小血管病(CSVD)的神经影像学特征总负担评分与认知障碍的关系。方法选取2016年6月-2019年5月于辽宁省金秋医院门诊就诊及住院的患者,年龄≥65岁,确诊CSVD的患者319名。采用脑小血管病总负担评分方法对无症状腔隙性梗死、脑白质病变、脑微出血及血管周围间隙扩大等4种CSVD神经影像学特征进行总体评估,记为0～4分。按分值分为轻度组(0分) 145例;中度组(1～2分) 131例和重度组(3～4分) 43例。应用简易智力状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,并进行统计学分析。结果 CSVD重度组年龄与CSVD总负担评分呈正相关(r=0. 841,P=0. 035)。在MMSE评分中,重度组在记忆力子项分值低于轻度组;中、重度组在回忆能力子项分值低于轻度组(P=0. 029、0. 036)。在MoCA评分中,重度组在记忆力、语言能力子项分值低于轻度组(P=0. 031、0. 029);中、重度组在视空间与执行能力、延迟回忆子项分值低于轻度组(P=0. 036、0. 014)。结论 CSVD总负担评分是导致全脑损害的脑小血管病有效的影像学评估手段,CSVD总负担加重与整体认知下降相关,是认知功能障碍的预测因素。多种神经影像学特征合并存在的老年脑小血管病在记忆、延迟回忆、视空间执行能力、语言能力4个认知领域受损更重。     

增龄相关性脑小血管病治疗新进展

随着全球预期寿命的延长，增龄相关性脑小血管病（cerebral small vessel disease，CSVD）患 病率不断增加。最近研究显示，深穿支动脉病（deep perforating arteriopathy，DPA）和脑淀粉样血管病 （cerebral amyloid angiopathy，CAA）均属于增龄相关性脑小血管病谱系（spectrum of age-related cerebral small vessel diseases）疾病，两者存在重叠性，且相互作用。增龄相关性CSVD治疗包括特异性及非特 异性治疗。非特异性治疗包括控制血管危险因素、抗血小板治疗及静脉溶栓等。特异性治疗方面，最 近研究提示抗炎治疗对增龄相关性CSVD或许有效；而针对CAA相关性炎症，已显示其对类固醇和（或） 环磷酰胺有良好的反应。随着对增龄相关性CSVD发病机制的进一步了解，未来可能会出现更多特异 性的治疗方法。     

Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.     

基于纤维束示踪的空间统计分析对脑小血管病合并阻塞性睡眠呼吸暂停患者脑微结构改变的研究

目的 采用弥散张量成像（diffusion tensor imaging,DTI）基于纤维束示踪的空间统计分析（tract-based spatial statistics,TBSS）方法探讨脑小血管病（cerebral small vessel disease,CSVD）合并阻塞性睡眠呼吸暂停（obstructive sleep apnea,OSA）患者的大脑微结构变化特点。方法 纳入于2018年9月—2020年6月在中山大学附属第一医院神经内科病房住院的CSVD患者,收集人口学信息、临床资料、认知功能评估量表评分、睡眠质量量表评分、CSVD常规影像学资料以及DTI、多导睡眠监测（polysomnography,PSG）参数等。以呼吸暂停低通气指数（apnea hypopnea index,AHI）5次/小时为界,分为OSA组（AHI≥5次/小时）与不伴OSA组（AHI＜5次/小时）,通过TBSS方法计算大脑白质存在差异的区域及其各向异性分数（fractional anisotropy,FA）和平均扩散系数（mean diffusivity,MD）,并对MD与睡眠监测参数、认知功能评分、CSVD影像标志物和CSVD负荷进行相关性分析。结果 本研究共纳入CSVD患者39例,其中7例因缺乏MRI数据/参数不一致/图像质量差而被排除,最终纳入32例患者。OSA组21例,平均年龄为（64.14±11.57）岁,男性18例（85.7%）;不伴OSA组11例,平均年龄为（67.64±8.95）岁,男性6例（54.5%）。TBSS分析显示,与不伴OSA组相比,OSA组在双侧丘脑前放射、双侧皮质脊髓束、双侧扣带回、双侧海马、大钳、小钳、双侧额枕下束、双侧上/下纵束、双侧钩束等部位的MD增加（P＜0.001）。双变量相关性分析发现,OSA组MD增加与脑白质高信号相对体积（r=0.646,P＜0.05）和Fazekas 2～3级（r=0.458,P<0.05）呈正相关,与MoCA评分呈负相关（r=-0.374,P＜0.05）,与MMSE评分、阿尔茨海默病评估量表-认知亚量表评分、睡眠质量评估量表、AHI、PSG参数、其他CSVD影像标志物及CSVD负荷之间无相关性（P＞0.05）。结论 CSVD合并OSA患者存在更为广泛的脑白质纤维损害,且大脑微结构广泛损害和脑白质高信号及认知功能障碍密切相关。     

Impact of obstructive sleep apnea on silent cerebral small vessel disease: a systematic review and meta-analysis

BackgroundCerebral small vessel disease (CSVD) is a well-known cause of vascular dementia, a leading medical morbidity in the aging population. Obstructive sleep apnea (OSA) has been validated as a cardiovascular risk factor. However, the relationship between these two clinical syndromes is not well established. We aimed to assess the association between OSA and CSVD.MethodsDatabases were searched from inception through May 2019. Studies that reported incidence or odd ratios of CSVD in patients with OSA were included. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird.ResultsA total of 14 observational studies comprising of 4335 patients were included into the analysis. Compared to patients without OSA, patients with OSA were significantly associated with CSVD magnetic resonance imaging (MRI) findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) with a pooled OR of 2.31 (95% confidence interval [CI], 1.46–3.66, I² = 79%) and 1.78 (95% CI, 1.06–3.01, I² = 41%), respectively. However, there was no significant association between OSA and findings of cerebral microbleeds (CMBs), with a pooled odds ratio (OR) of 2.15 (95% CI, 0.64–7.29, I² = 55%).ConclusionsOur study demonstrated the association between OSA and CSVD MRI findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) when compared to patients without OSA. The absence of an association of CMBs findings with OSA could be due either by a lower sensitivity of neuroimaging techniques utilized to detect CMBs or a potentially different pathogenesis of CMBs.     

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target

Objective

This study aimed to investigate the relationships of heart rate variability (HRV) with the presence, severity, and individual neuroimaging markers of cerebral small vessel disease (CSVD).

Method

A total of 4676 participants from the Third China National Stroke Registry (CNSR-III) study were included in this cross-sectional analysis. CSVD and its markers, including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA), were evaluated. Two common HRV parameters, including the square root of the mean of the sum of the squares of differences between adjacent N–N intervals (RMSSD) and the standard deviation of all N–N intervals (SDNN), were used to evaluate the function of the autonomic nervous system (ANS). Binary or ordinal logistic regression analyses were performed to investigate the association between HRV and CSVD. In addition, two-sample mendelian randomization (MR) analyses were performed to investigate the causality of HRV with CSVD.

Results

RMSSD was significantly associated with total burden of CSVD (Wardlaw's scale, common odds ratio [cOR] 0.80, 95% confidence interval [CI] 0.67–0.96, p = 0.02; Rothwell's scale, cOR 0.75, 95% CI 0.60–0.93, p = 0.008) and the presence of CSVD (Rothwell, OR 0.75, 95% CI 0.60–0.93, p = 0.008). However, no significant associations between SDNN and the presence or total burden of CSVD were observed. Moreover, RMSSD was related to WMH burden (OR 0.80, 95% CI 0.66–0.96, p = 0.02), modified WMH burden (cOR 0.82, 95% CI 0.69–0.97, p = 0.02), and Deep-WMH (OR 0.75, 95% CI 0.62–0.91, p = 0.003), while SDNN was related to Deep-WMH (OR 0.80, 95% CI 0.66–0.96, p = 0.02) and BA (cOR 0.80, 95% CI 0.68–0.95, p = 0.009). Furthermore, adding HRV to the conventional model based on vascualr risk factors enhanced the predictive performance for CSVD, as validated by the integrated discrimination index (p < 0.05). In addition, no causality between HRV and CSVD was observed in two-sample MR analyses.

Conclusion

Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.     

缺血性脑卒中患者合并脑微出血的危险因素分析

目的探讨缺血性脑卒中(cerebral ischemic stroke,IS)患者合并脑微出血(cerebral microbleeds,CMBs)的危险因素。方法回顾性收集2015年1月至2017年5月作者医院神经内科连续收治的IS住院患者1631例,根据是否存在CMBs分为合并CMBs组703例和未合并CMBs组928例。分析两组间性别构成、年龄、血压、体重、体重指数(body mass index,BMI)、血糖、尿酸、三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-c)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-c)、载脂蛋白A(apolipoproteins A,apoA)、载脂蛋白B(apolipoproteins B,apoB)、吸烟史、饮酒史、高血脂史、糖尿病史、高血压史、心脏疾病史、脑白质高信号(white matter hyperintensity,WMH)的差异,并采用多因素Logistic回归分析影响IS患者发生CMBs的危险因素。结果与未合并CMBs组比较,合并CMBs组患者年龄大,男性、吸烟、饮酒、高血压、糖尿病、WMH构成比例高,空腹血糖、尿酸水平高(均P<0.05),而空腹LDL-c和apoA水平较低(均P<0.05)。多因素Logistic回归分析显示吸烟(OR=5.791,95%CI:3.714~9.031,P<0.01)、饮酒(OR=7.306,95%CI:4.926~10.835,P<0.01)、高血压(OR=2.162,95%CI:1.487~3.143,P<0.01)、WMH(OR=3.249,95%CI:1.594~6.625,P<0.01)、LDL-c(OR=0.789,95%CI:0.630~0.989,P<0.05)、apoA(OR=0.696,95%CI:0.369~0.753,P<0.01)是IS合并CMBs的独立危险因素。结论吸烟、饮酒、高血压、WMH、LDL-c、apoA是IS合并CMBs的独立危险因素,且LDL-c和apoA水平下降与CMBs发生增加相关。     

Reduced blood flow in normal white matter predicts development of leukoaraiosis

The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61±11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.     

Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease

Pathological relationships between damage to the deep white matter of the cerebral cortex [as evidenced by myelin loss (ML)], cerebral amyloid angiopathy (CAA) and arteriosclerosis (ART) were investigated in the brains of 137 patients with autopsy-confirmed Alzheimer's disease (AD), in order to better understand the causes of white matter damage in AD, and the contribution of this to the pathogenesis of the disorder. All 137 patients had some degree of CAA in one or more brain regions although the occipital cortex was severely affected by CAA more frequently, and consequently mean CAA severity score was significantly greater, than other cortical regions. Eighty-seven patients (63.5%) were affected by ML, with more patients showing ML from occipital cortex than from other cortical regions leading to a significantly higher mean ML severity score in this region. One hundred and twenty-six patients (92%) were affected by ART, although the occipital cortex was not more frequently affected by ART than other cortical areas, the mean ART severity score in occipital cortex was nonetheless significantly greater than that of frontal and temporal cortex. Eighty-seven patients showed both CAA and ML, although there was only a weak correlation between degree of CAA and extent of ML (P = 0.035). Forty-seven patients showed ML and significant ART, 16 patients showed significant ART but no ML, 40 patients showed ML in the absence of significant ART and 34 patients showed neither significant ART nor ML. Overall, and for each of the four brain regions, the extent of ML correlated significantly (P < 0.001) with degree of ART. However, when only those 47 patients with ML and significant ART were considered, much stronger correlations between the extent of ML and the degree of ART were achieved both overall and within each of the four brain regions. The overall ART severity score (and overall scores for each pathological marker of ART) significantly correlated with that of CAA (P < 0.001). Pathological processes leading to white matter damage, in terms of ML at least, in AD are thus likely to be heterogeneous. Many patients suffer ML in association with ART, but in others ML cannot be explained by presence of ART or CAA. In such patients, autoregulatory changes in blood vessels might be responsible for ML. The association between the extent of CAA and ART suggests shared risk factors for each pathological change.     

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。     

Contributors to white matter damage in the frontal lobe in Alzheimer's disease

Abnormalities of cerebral white matter are present in a majority of patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction and cognitive impairment. The white matter abnormalities are usually attributed to degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In the present study we examined sections of frontal lobe from 125 autopsy-confirmed cases of AD and assessed the relationship of degenerative large and small vessel disease, CAA, parenchymal Abeta load and APOE genotype, to several objective measures of white matter damage: extent of immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation of amyloid precursor protein (APP), axon density in superficial and deep white matter, and intensity of staining for myelin. We found no association between atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter damage. However, labelling of white matter for GFAP correlated strongly with the parenchymal Abeta load (P = 0.0003) and with APP accumulation (P = 0.008). Our findings suggest that severity of frontal white matter damage in AD is closely related to parenchymal Abeta load and that in most cases the contribution of degenerative vascular disease, CAA and APOE is relatively minor.