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Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review 导致 CADASIL 或 CADASIL 样脑小血管疾病的最常见 NOTCH3 突变:系统回顾
Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2024.100227
Georgina Boston , Dan Jobson , Toshiki Mizuno , Masafumi Ihara , Raj N Kalaria

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a monogenic disorder caused by mutations in the NOTCH3 gene. The main aim of our survey was to determine if there is an association between phenotypes and genotypes across the most common NOTCH3 mutations found in CADASIL patients. We systematically searched clinical studies and genomic databases from 1996 to 2023 to first identify the most common mutations responsible for CADASIL. We found the six most common NOTCH3 missense mutations globally were the p.R75P, p.R133C, p.R141C, p.R169C, p.R182C, and p.R544C, of which p.R133C was described to occur most often. Focusing on studies with comprehensive clinical records, our analysis further suggested that the p.R75P, p.R141C, p.R182C and p.R544C genotypes were highly congruent with the presence of white matter hyperintensities on magnetic resonance imaging (MRI), which was the most common phenotypic characteristic across all four mutations. We found the p.R141C mutation was associated with increased severity of disease. We also found the average age of onset in p.R544C carriers was more than a decade later compared to the p.R141C carriers. However, statistical analysis showed there were no overall differences between the phenotypic characteristics of the two common mutations, p.R141C and p.R544C. Geographically, China and Japan were the only two countries to report all the four common mutations vis a vis p.R75P, p.R141C, p.R182C and p.R544C. There is a possibility that this is due to a combination of a founder effect, but there also could be sampling biases.

脑常染色体显性动脉病伴有皮层下梗塞和白质脑病(CADASIL)是一种由NOTCH3基因突变引起的单基因疾病。我们调查的主要目的是确定 CADASIL 患者中最常见的 NOTCH3 基因突变的表型与基因型之间是否存在关联。我们系统地搜索了 1996 年至 2023 年的临床研究和基因组数据库,首先确定了导致 CADASIL 的最常见突变。我们发现全球最常见的六种 NOTCH3 错义突变是 p.R75P、p.R133C、p.R141C、p.R169C、p.R182C 和 p.R544C,其中 p.R133C 的发生率最高。我们的分析侧重于具有全面临床记录的研究,进一步表明 p.R75P、p.R141C、p.R182C 和 p.R544C 基因型与磁共振成像(MRI)上出现的白质高密度高度一致,而白质高密度是所有四种突变中最常见的表型特征。我们发现 p.R141C 突变与疾病的严重程度增加有关。我们还发现,p.R544C 基因携带者的平均发病年龄比 p.R141C 基因携带者晚了十多年。不过,统计分析显示,p.R141C 和 p.R544C 这两种常见突变的表型特征总体上没有差异。从地域上看,中国和日本是仅有的两个报告了所有四种常见突变(p.R75P、p.R141C、p.R182C 和 p.R544C)的国家。这有可能是创始人效应的综合结果,但也可能存在抽样偏差。
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引用次数: 0
What have clinical trials taught us about brain health? 临床试验对大脑健康有何启示?
Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2023.100199
Keon-Joo Lee , Hee-Joon Bae

The Global Burden of Disease Study projects an almost tripling of dementia cases worldwide in the next 30 years making it important to recognize and understand modifiable risks and preventatives for cognitive impairment. Recent studies suggest that prevention or treatment of cardiovascular risks may be an important strategy to prevent or slow the progression of cognitive impairment. In 2017, the American Heart Association and American Stroke Association introduced metrics for "optimal brain health". These metrics defined brain health in terms of ideal health behaviors and factors.

Since then and leading up to 2017, a number of clinical trials have been conducted to investigate the potential of modification of cardiovascular risks on prevention of dementia or cognitive impairment and thus, enhancement of brain health. This discussion is a review of findings from clinical trials focusing on interventions, including antihypertensive agents, glycemic control and lipid-lowering therapies, multidomain approaches, and antithrombotic medications. Notably, the results highlight the promise of intensive blood pressure lowering strategies and multidomain approaches, as evidenced by the FINGER trial. The review also discusses the potential of treatment or prevention of cerebral small vessel disease (cSVD) and the application of Mendelian randomization as a strategy to preserve brain structure and function.

全球疾病负担研究》预测,在未来 30 年内,全球痴呆症病例将增加近两倍,因此认识和了解认知障碍的可改变风险和预防措施非常重要。最近的研究表明,预防或治疗心血管风险可能是预防或减缓认知障碍进展的重要策略。2017 年,美国心脏协会和美国卒中协会推出了 "最佳脑健康 "指标。这些指标从理想的健康行为和因素的角度定义了脑健康。从那时起到 2017 年之前,已经开展了多项临床试验,研究改变心血管风险对预防痴呆或认知障碍,从而增强脑健康的潜力。本讨论是对临床试验结果的回顾,重点是干预措施,包括降压药、血糖控制和降脂疗法、多领域方法和抗血栓药物。值得注意的是,研究结果强调了强化降压策略和多领域方法的前景,FINGER 试验就是证明。综述还讨论了治疗或预防脑小血管疾病(cSVD)的潜力,以及孟德尔随机化作为一种保护大脑结构和功能的策略的应用。
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引用次数: 0
Examining the relationship between anxiety and regional brain volumes in the National Alzheimer's Coordinating Center uniform, imaging, and biomarker datasets 在国家阿尔茨海默氏症协调中心统一、成像和生物标记数据集中研究焦虑与区域脑容量之间的关系
Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2024.100201
Shanna L. Burke , Adrienne Grudzien , Tan Li , Marlou Abril , Wupeng Yin , Tahirah A. Tyrell , Christopher P. Barnes , Kevin Hanson , Steven T. DeKosky

Anxiety has been associated with a greater risk of Alzheimer's disease (AD). Existing research has identified structural differences in regional brain tissue in participants with anxiety, but results have been inconsistent. We sought to determine the association between anxiety and regional brain volumes, and the moderation effect of APOE ε4. Using data from participants in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set, with complete imaging (MRI) and biomarker data (n = 1533), multiple linear regression estimated the adjusted effect of anxiety on 30 structural MRI regions. The moderation effect of APOE ε4 on the relation between structural MRI regions and anxiety was assessed as was the moderation effect of cognitive status. False discovery rate was used to adjust for multiple comparisons. After controlling for intracranial volume, age, sex, years of education, race, Hispanic ethnicity, and cognitive status, seven MRI regions demonstrated lower volumes among participants with anxiety: total cerebrum gray matter volume, right hippocampus volume, hippocampal volume (total), right and left frontal lobe cortical gray matter volume, and right and total temporal lobe cortical gray matter volume. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions, with corresponding ventricular enlargement. Future research should investigate if anxiety-related changes to brain morphology contribute to greater AD risk.

焦虑与阿尔茨海默病(AD)的高风险有关。现有研究发现,焦虑症患者的区域脑组织存在结构性差异,但结果并不一致。我们试图确定焦虑与区域脑容量之间的关系,以及 APOE ε4 的调节作用。通过使用国家阿尔茨海默氏症协调中心(NACC)统一数据集中具有完整成像(MRI)和生物标记物数据(n = 1533)的参与者的数据,多元线性回归估算了焦虑对 30 个结构性 MRI 区域的调整效应。评估了 APOE ε4 对结构性 MRI 区域与焦虑之间关系的调节作用,以及认知状态的调节作用。假发现率用于调整多重比较。在控制了颅内容积、年龄、性别、受教育年限、种族、西班牙裔和认知状况后,七个核磁共振成像区域在焦虑参与者中显示出较低的容积:大脑灰质总容积、右侧海马容积、海马容积(总)、右侧和左侧额叶皮质灰质容积以及右侧和颞叶皮质灰质总容积。研究结果表明,焦虑与多个脑区的显著萎缩以及相应的脑室扩大有关。未来的研究应探讨与焦虑相关的大脑形态变化是否会导致更高的注意力缺失症风险。
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引用次数: 0
The Luigi Sacco Hospital VAS-COG stroke care pathway: A five-year experience Luigi Sacco 医院 VAS-COG 中风护理路径:五年经验
Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2024.100210
I. Cova , F. Mele , A. Nicotra , G. Maestri , V. Cucumo , S. Pomati , E. Salvadori , L. Pantoni

Background

Psycho-cognitive consequences are a frequent cause of disability in stroke survivors but are often underdiagnosed also because of lack of services dedicated to these aspects. We started assessing systematically cognitive and behavioral functions in acute stroke patients and to follow them up. Here, we report a retrospective analysis of the organization of the Sacco VAS-COG stroke care pathway and the refinements implemented during 5 years of activity.

Methods

The protocol includes baseline collection of clinical history, general and neurologic examinations, functional, neuropsychological, and neuroimaging assessment. At follow-up, a diagnosis of cognitive decline was made based on best clinical judgment in the first period (January 2018 to May 2019, namely VAS-COG protocol 1.0) and then based on an extensive neuropsychological battery (May 2019 to January 2023, namely VASCOG protocol 2.0); psychiatric and behavioral disturbances are investigated through suitable scales.

Results

From January 2018 to December 2022, 834 patients (mean age 76±13.6 years; 46.6 % females) with acute cerebrovascular events were admitted to the stroke unit, mostly (80 %) for ischemic strokes. Pre-event cognitive impairment was not assessable in 78 patients (9.3 %) because no reliable informant was present and was reported in 327/756 (43 %) patients. During follow-up, post-stroke cognitive impairment was detected in 124/217 (57.1 %) patients in VAS-COG protocol 1.0 and in 137/201(68.2 %) patients in VAS-COG protocol 2.0, while 95/218 (43.2 %) patients were found to be depressed and patients presented on average 2.5 neuropsychiatric symptoms on Neuropsychiatric Inventory-questionnaire.

Conclusions

The VAS-COG stroke care pathway represents a model for patients and for their families.

背景心理认知后果是中风幸存者致残的一个常见原因,但由于缺乏专门针对这些方面的服务,往往诊断不足。我们开始系统地评估急性中风患者的认知和行为功能,并对他们进行随访。在此,我们报告了对 Sacco VAS-COG 中风护理路径组织的回顾性分析,以及在 5 年活动中实施的改进。随访时,根据第一阶段(2018 年 1 月至 2019 年 5 月,即 VAS-COG 协议 1.0)的最佳临床判断做出认知功能衰退的诊断,然后根据广泛的神经心理学电池(2019 年 5 月至 2023 年 1 月,即 VASCOG 协议 2.结果2018年1月至2022年12月,卒中单元共收治了834名急性脑血管事件患者(平均年龄76±13.6岁;46.6%为女性),其中大部分(80%)为缺血性卒中。有 78 名患者(9.3%)因没有可靠的信息提供者而无法对事件发生前的认知障碍进行评估,有 327/756 名患者(43%)报告了事件发生前的认知障碍。在随访期间,VAS-COG 方案 1.0 的 124/217 例(57.1%)患者和 VAS-COG 方案 2.0 的 137/201 例(68.2%)患者发现了卒中后认知功能障碍,而 95/218 例(43.2%)患者被发现患有抑郁症,患者在神经精神病学调查问卷中平均出现 2.5 种神经精神病学症状。
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引用次数: 0
DIFFUSION MRI HARMONIZATION ENABLES JOINT-ANALYSIS OF MULTICENTRE DATA OF PATIENTS WITH CEREBRAL SMALL VESSEL DISEASE 弥散核磁共振成像协调实现了对脑小血管疾病患者多中心数据的联合分析
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2022.100104
Bruno Miguel de Brito Robalo , Geert Jan Biessels , Christopher Chen , Anna Dewenter , Marco Duering , Saima Hilal , Huiberdina L. Koek , Anna Kopczak , Bonnie Lam , Alexander Leemans , Vincent Mok , Laurien P. Onkenhout , Hilde van den Brink , Alberto de Luca
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引用次数: 0
THE IMPACT OF ALZHEIMER BIOMARKERS AND VASCULAR FACTORS ON COGNITIVE DECLINE IN MEMORY CLINIC PATIENTS 阿尔茨海默氏症生物标志物和血管因素对记忆门诊患者认知能力下降的影响
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2022.100051
Veerle van Gils , Willemijn J. Jansen , Domantė Kučikienė , Ana Sofia Costa , Jörg B. Schulz , Frans Verhey , Kathrin Reetz , Stephanie J.B. Vos
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引用次数: 0
AGE-ASSOCIATED CHANGES IN THE RENIN-ANGIOTENSIN SYSTEM: IMPLICATIONS FOR FUTURE CLINICAL TRIALS 肾素-血管紧张素系统与年龄有关的变化:对未来临床试验的影响
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2022.100090
Robert MacLachlan, Scott Miners, Patrick Kehoe
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引用次数: 0
THE RELATIONSHIP OF ACUTE DELIRIUM WITH COGNITIVE AND EMOTIONAL SYMPTOMS AFTER STROKE: A LONGITUDINAL STUDY 中风后急性谵妄与认知和情绪症状的关系:一项纵向研究
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2022.100088
Vilde Nerdal , Elise Gjestad , Ragnhild Munthe-Kaas , Ingvild Saltvedt , Stian Lydersen , Ramune Grambaite
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引用次数: 0
Astaxanthin and improvement of dementia: A systematic review of current clinical trials 虾青素与改善痴呆症:当前临床试验的系统回顾
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2024.100226
Nunki Puspita Utomo, Rizaldy Taslim Pinzon, Patrick Kurniawan Latumahina, Kadex Reisya Sita Damayanti

Worldwide, the incidence of neurodegenerative diseases especially dementia is steadily increasing due to the aging population. Abundant research emerges on the probability of combating or preventing the degeneration process, with the most established one being to tackle the existence of oxidative stress and free radicals production due to their nature of aggravating dementia. Astaxanthin, a marine carotenoid, was proven to be a protective agent of cerebral ischemia through many animal model clinical trials. This review summarizes the evidence of Astaxanthin's benefits for cognitive function across clinical trials done in older age. The results are of interest as its supplementation does not exhibit unwanted issues on the consumer based on physical and laboratory examinations. Despite not being supported statistically, however, subjective and objective cognitive amelioration were reported according to the majority of this review's trial subjects. Although there is no clear and direct mechanism for cognitive improvement by Astaxanthin activity in the body systems, the encouragement of Astaxanthin supplementation should be considered as the elderly with dementia may highly benefit from the improved cognitive function.

在世界范围内,由于人口老龄化,神经退行性疾病尤其是痴呆症的发病率正在稳步上升。关于抗击或预防退化过程的可能性的研究层出不穷,其中最成熟的研究是解决氧化应激和自由基产生的问题,因为它们具有加重痴呆症的性质。虾青素是一种海洋类胡萝卜素,通过许多动物模型临床试验证明,虾青素对脑缺血具有保护作用。本综述总结了在老年临床试验中虾青素对认知功能有益的证据。根据身体检查和实验室检查,补充虾青素不会对消费者造成不必要的影响,因此这些结果值得关注。尽管没有得到统计学上的支持,但本综述的大多数试验对象都报告了主观和客观的认知功能改善情况。虽然虾青素在人体系统中的活性对认知能力的改善没有明确的直接机制,但应考虑鼓励补充虾青素,因为患有痴呆症的老年人可能会从认知功能的改善中获益匪浅。
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引用次数: 0
INVESTIGATING THE RISK OF CARDIOVASCULAR RISK FACTOR SUBGROUPS IN COGNITIVELY NORMAL ELDERLY ON ALZHEIMER'S DISEASE: A LATENT CLASS APPROACH 调查认知正常的阿尔茨海默氏症老年人心血管风险因素亚群的风险:潜类方法
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.cccb.2022.100087
Myuri Ruthirakuhan , Hugo Cogo-Moreira , Walter Swardfager , Nathan Herrmann , Krista Lanctot , Sandra Black
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引用次数: 0
期刊
Cerebral circulation - cognition and behavior
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