Motor cortex hyperexcitability in subcortical ischemic vascular dementia

To study whether in subcortical ischemic vascular dementia (SIVD) the changes of motor cortex excitability are due to the dementing process or to the cerebrovascular lesions, we examined 20 SIVD patients, 20 patients with subcortical ischemic disease without dementia (SIDWD) and 20 control subjects who underwent transcranial magnetic stimulation (TMS). Motor threshold (MT), amplitudes of motor evoked potentials (MEPs) and silent period (SP) were considered. MT in SIVD patients (32.7 ± 2.6%) was significantly lower (p < 0.001) than in SIDWD patients (47.9 ± 3.4%) and in controls (49.1 ± 4.2%). MEP amplitude was larger in SIVD patients (6.8 ± 1.7 mV) than in the other groups (5.7 ± 1.9 mV and 5.2 ± 1.8 mV, p < 0.02). Motor cortex excitability is enhanced in SIVD. Our data, taken together with previous results in Alzheimer disease (AD), indicate that motor cortex hyperexcitability is a common finding in different dementing illnesses.     

Genetics of subcortical vascular dementia

Subcortical vascular dementia or cerebral small vessel disease is a common cause of disability in the elderly. On magnetic resonance imaging the disease is manifested as white matter lesions, lacunes and microbleeds. Its etiology is complex, with age and hypertension as established risk factors. The heritability of white matter lesions is constantly high over different populations. Linkage studies identified several loci for these lesions however no genes responsible for the linkage signals had been identified so far. Results from genetic association studies using the candidate gene approach support the role of APOE, the renin–angiotensin system, as well as the Notch3 signaling pathway in the development of subcortical vascular dementia. The recent genomegenome wide association study on white matter lesions identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoints to possible novel mechanisms leading to these lesions.     

额颞叶痴呆的蛋白质组研究

目的 为深入理解额颞叶痴呆分子机制并寻找诊断治疗该疾病的蛋白质标记物,选取5例经病理证实的额颞叶痴呆患者与4例无神经系统疾病老年人尸检脑标本进行蛋白质组学研究.方法 死亡24 h内新鲜取材的尸检额叶、颞叶蛋白质以固相pH梯度等电聚焦为第一向,SDS-PAGE垂直电泳为第二向进行双向电泳（2-DE）,图象分析软件Imagemaster 2D Elite分析电泳图谱,MALDI-TOF质谱或MALDI-TOF/TOF串联质谱鉴定蛋白质.结果 18种蛋白质的表达量在额颢叶痴呆患者与正常老年人显著不同.12个在额颞叶痴呆表达量上调的蛋白质被鉴定为3-磷酸甘油醛脱氢酶、尿嘧啶DNA糖苷水解酶、Cu-Zn超氧化物歧化酶、异柠檬酸脱氢酶亚单位、synaptotagmin I、Peroxiredoxin2、胶质纤维酸性蛋白、P25 alpha、烯酰辅酶A水合酶短链1、吡哆醇-5′-磁酸氧化酶、Mn超氧化物歧化酶、α-烯醇化酶;6个在额颞叶痴呆表达量下调的蛋白质被鉴定为抗氧化蛋白2（酸性钙离子依赖型磷脂酶A）、铁蛋白H链、谷氨酸脱氢酶、肽基脯氨酸顺反异构酶A、血清白蛋白前体、二氢嘧啶酶相关蛋白2.结论 额颞叶痴呆患者脑组织中神绛纤维缠结相关蛋白、氧应激蛋白、凋亡相关蛋白及重要代谢酶的表达发生变化,有助于深入理解额颞叶痴呆分子机制并有望在额颞叶痴呆的早期诊断及新药开发上发挥作用.     

Management of the behavioral and psychological symptoms of dementia

More than 50% of people with dementia experience behavioral and psychological symptoms of dementia (BPSD). BPSD are distressing for patients and their caregivers, and are often the reason for placement into residential care. The development of BPSD is associated with a more rapid rate of cognitive decline, greater impairment in activities of daily living, and diminished quality of life (QOL). Evaluation of BPSD includes a thorough diagnostic investigation, consideration of the etiology of the dementia, and the exclusion of other causes, such as drug-induced delirium, pain, or infection. Care of patients with BPSD involves psychosocial treatments for both the patient and family. BPSD may respond to those environmental and psychosocial interventions, however, drug therapy is often required for more severe presentations. There are multiple classes of drugs used for BPSD, including antipsychotics, anticonvulsants, antidepressants, anxiolytics, cholinesterase inhibitors and NMDA modulators, but the evidence base for pharmacological management is poor, there is no clear standard of care, and treatment is often based on local pharmacotherapy customs. Clinicians should discuss the potential risks and benefits of treatment with patients and their surrogate decision makers, and must ensure a balance between side effects and tolerability compared with clinical benefit and QOL.     

Systematic review of statins for the prevention of vascular dementia or dementia

Aim: Non‐hypolipidemic effects of statins, known as pleiotropic effects, are likely to explain the effect of statins on dementia. Results of the relationship between statins and dementia in previous studies are conflicting. There is no systematic review investigating the effect of statins on vascular dementia (VaD). This systematic review evaluates the role of statins in the prevention of VaD or dementia. The possible causes of conflicting results in the existing published work will be explored. Methods: Relevant studies were systematically identified and reviewed. The Cochrane Controlled Trials and three electronic databases (MEDLINE, EMBASE and PsycInfo) were searched. The selection criteria were defined a priori. Included studies were rated by quality assessment checklists and two independent reviewers. Results: Six studies in dementia, two studies in VaD (one study reported both dementia and VaD) and two meta‐analyses met the selection criteria. The studies covered 1372 cases of dementia from 14 430 participants and 116 cases of VaD from 4924 participants from the USA and UK. There was no association between statin use and risk of VaD. The protective effect of statins on dementia was demonstrated only in a nested case–control study of lower quality and one recently published cohort study. In most other cohort and high quality studies, statin use did not show a beneficial effect. Conclusion: Study design differences among the studies and methodological shortcomings may have resulted in different outcomes. On the basis of these conflicting results, statins could not be recommended as a preventative treatment for dementia.     

血管性痴呆的发病机制

对血管性痴呆(vascula dementia,VD)的命名历史、主要发病机制及组织病理学改变进行了系统的论述。脑血管损害、脑白质疏松以及Alz11eimer病(AD)样的组织学改变可能是VD发生的机制,这些因素在VD的发病过程中又有着必然的联系.     

Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies

Aim: The behavioral and psychological symptoms of dementia place a heavy burden on caregivers. Antipsychotic drugs, though used to reduce the symptoms, frequently decrease patients' activities of daily living and reduce their quality of life. Recently, it was suggested that ferulic acid is an effective treatment for behavioral and psychological symptoms. We have also reported several patients with dementia with Lewy bodies showing good responses to ferulic acid and Angelica archangelica extract (Feru‐guard). The present study investigated the efficacy of Feru‐guard in the treatment of behavioral and psychological symptoms in frontotemporal lobar degeneration and dementia with Lewy bodies. Methods: We designed a prospective, open‐label trial of daily Feru‐guard (3.0 g/day) lasting 4 weeks in 20 patients with frontotemporal lobar degeneration or dementia with Lewy bodies. Behavioral and psychological symptoms of dementia were assessed at baseline and 4 weeks after the start of treatment, using the Neuropsychiatric Inventory. The Neuropsychiatric Inventory scores were analyzed using the Wilcoxon rank sum test. Results: Treatment with Feru‐guard led to decreased scores on the Neuropsychiatric Inventory in 19 of 20 patients and significantly decreased the score overall. The treatment also led to significantly reduced subscale scores on the Neuropsychiatric Inventory (“delusions”, “hallucinations”, “agitation/aggression”, “anxiety”, “apathy/indifference”, “irritability/lability” and “aberrant behavior”). There were no adverse effects or significant changes in physical findings or laboratory data. Conclusion: Feru‐guard may be effective and valuable for treating the behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatr Gerontol Int 2011; 11: 309–314.     

Characteristics of cognitive function,behavioral and psychological symptoms in patients with Alzheimer's disease versus behavioral variant frontotemporal dementia

正Objective To compare the differences in cognitive function and behavioral and psychological symptoms between patients with Alzheimer's disease(AD)and behavioral variant frontotemporal dementia(bv FTD).Methods Thirty-six AD patients and 20 bv FTD patients on mild-to-moderate stage,who were biomarkerconfirmed by positron emission tomography(PET),were     

血管性痴呆的危险因素探讨

目的　探讨血管性痴呆(vasculardementia ,VD)可能的危险因素。方法　临床诊断为很可能VD患者111例,性别、职业和受教育程度相匹配的认知功能正常老年人15 5例为对照,以logistic回归模型分析各种危险因素如高血压、糖尿病、冠心病、短暂性脑缺血发作等与VD的关系。结果　单因素分析显示,高血压、糖尿病、冠心病、心脏传导阻滞、短暂性脑缺血发作、慢性阻塞性肺疾病、高脂血症、贫血病史以及年龄与VD有关;多因素分析证实贫血、高血压、糖尿病、短暂性脑缺血发作和冠心病与VD有关,OR值(95 %CI)依次为5 .15 (2 .31～11.4 8) ,4 .11(2 .0 3～8.32 ) ,2 .15 (1.17～3.94 ) ,2 .0 8(1.12～3.86 ) ,2 .0 4 (1.0 7～3.87)。结论　贫血、高血压、糖尿病、短暂性脑缺血发作和冠心病与VD有关,可能是VD的独立危险因素。     

皮质下缺血性血管性痴呆的诊断和治疗

皮质下缺血性血管性痴呆主要以小血管疾病为病因,包括腔隙状态、关键部位梗死性痴呆和Binswanger综合征,临床上表现为皮质下综合征和认知障碍.积极诊断和治疗皮质下缺血性血管性痴呆有助于降低老年人认知障碍的发病风险.     

痴呆及其心理、行为症状与血浆同型半胱氨酸水平关系

目的 探讨痴呆及痴呆心理和行为症状(Psychological and behavioral symptoms of dementia，BPSD)的可能发病机制，研究血浆同型半胱氨酸(homocysteine，Hcy)水平与痴呆及BPSD的关系。方法 阿尔茨海默病(Alzheimer Disease，AD)、混合性痴呆(Mixed dementia，MD)、血管性痴呆(Vascular dementia，VD)和正常对照组各30例参加本研究。采用Alzheimer病行为症状评定量表(The Behavioral Pathlology in Alzheimer Disease Rating Scale，BEHAVE-AD)评定痴呆患者BPSD。采用高压毛细血管电泳紫外检测法测定经2，4-二硝基氟苯(2，4-dimntrifluorobenzen，DNFB)衍生后的血浆Hcy水平。结果 AD、MD和VD患者血浆Hcy浓度均显著高于正常对照组，血浆高Hcy水平的痴呆患者BEHAVE-AD总分较高。结论 血浆高Hcy水平不仅与痴呆的发生发展有关，且在痴呆患者BPSD的发病机制中扮演了一个重要角色。     

血管性痴呆危险因素的研究现状

随着人口老龄化加剧,血管性痴呆（VD）的发病率呈上升趋势。VD的发生是一个多因素致病过程,其危险因素包括年龄、性别、受教育程度、脑血管病、高血压、糖尿病、高血脂、烟酒嗜好、心脏病、贫血、ApoE基因、高同型半胱氨酸等。VD为目前唯一可以防治的痴呆,积极预防其危险因素,可以减少VD发生,因此探索VD的危险因素显得尤为重要。本文就VD的危险因素研究现状作一综述。     

天麻素联合多奈哌齐治疗血管性痴呆疗效分析

目的观察天麻素与多夸哌齐联合治疗血管性痴呆的临床治疗效果。方法我们采用随机、对照研究的方法,将48例老年血管性痴呆患者分为多奈哌齐组（对照组）、多奈哌齐联合天麻素治疗组（联合治疗组）,观察2组患者简易智能量表、日常生活功能量表、Hachinski缺血量表及脑电图等指标的变化,并观察不良反应。结果研究显示2组痴呆量表评分、生活质量评分及脑电图表现均有明显改善,而药联合治疗组改善更明显,与对照组比较有统计学差异。结论天麻素联合多奈哌齐能改善血管性痴呆患者生活质量及脑功能。     

高同型半胱氨酸血症与皮质下缺血性血管病患者认知功能障碍的关系

目的探讨高同型半胱氨酸血症(Hhcy)及叶酸、维生素B12缺乏与皮质下缺血性血管病(SIVD)不同程度认知功能障碍的相关性。方法将119例SIVD患者按照简易精神状态量表(MMSE)认知功能程度的不同分为痴呆组与非痴呆组。其中痴呆组54例,非痴呆组65例。对所有受试者检测其同型半胱氨酸(Hcy)及血清叶酸、维生素B12水平。结果痴呆组血浆Hcy水平为(43±9)μmol/L,显著高于非痴呆组的(20±6)μmol/L(P<0.01);血清叶酸和维生素B12水平分别为(8±4)nmol/L、(290±154)pmol/L,显著低于非痴呆组的(13±3)nmol/L、(504±141)pmol/L(均P<0.01)。采用Spearm an相关方法分析,显示不同性别的Hcy水平与MMSE分数均呈负相关(男:r=-0.685,女:r=-0.689,二者均P<0.01),与年龄均呈正相关(男:r=-0.592,女:r=0.576,二者均P<0.01);Hcy水平与糖尿病、血脂、高血压、吸烟、饮酒等其他危险因素无明显相关性(P>0.05)。结论伴随血浆Hcy水平增高SIVD认知功能障碍程度加重,Hhcy可能是SIVD认知功能障碍的独立危险因素,叶酸、维生素B12缺乏是间接引起Hhcy,而导致SIVD重要的营养因素。     

Incidence of dementia,Alzheimer's disease,and vascular dementia in Italy. The ILSA Study

OBJECTIVES: To estimate the incidence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older Italians and evaluate the relationship of age, gender, and education to developing dementia. DESIGN: Cohort incidence study in the context of the Italian Longitudinal Study on Aging. SETTING: Population sample from eight Italian municipalities. PARTICIPANTS: A dementia-free cohort of 3,208 individuals (aged 65-84), individuated after a baseline evaluation performed in 1992 / 93, aimed at detecting prevalent cases. MEASUREMENTS: The dementia-free cohort was reexamined in 1995 to identify incident cases. The Mini-Mental State Examination (cutoff 23 / 24) was employed to screen for dementia. Trained neurologists evaluated the individuals who screened positive. Final diagnoses had to meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for dementia, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and International Classification of Diseases, Tenth Revision criteria for VaD. RESULTS: Before the follow-up examination, 382 individuals had died (232 had reliable information). Of the 2,826 survivors, 2,266 completed the study. Overall, 127 new dementia cases were identified. Average incidence rates per 1,000 person-years were 12.47 (95% confidence interval (CI)=10.23-14.72) for dementia, 6.55 (95% CI=4.92-8.17) for AD, and 3.30 (95% CI=2.14-4.45) for VaD. Both AD and VaD showed age-dependent patterns. Education was protective against dementia and AD. Women carried a significantly higher risk of developing AD (hazard ratio=1.67, 95% CI=1.02-2.75), and men of developing VaD (hazard ratio=2.23, 95% CI=1.06-4.71). CONCLUSIONS: Incidence of dementia in Italy paralleled that in most industrialized countries. About 150,000 new cases per year are expected. A significant gender effect was evidenced for major dementia subtypes. The burden of VaD, especially in men, offers opportunities for prevention.     

Korean Addenbrooke's Cognitive Examination Revised (K‐ACER) for differential diagnosis of Alzheimer's disease and subcortical ischemic vascular dementia

Aim: Sensitive, specific neuropsychological screening tests, such as the Addenbrooke's Cognitive Examination Revised (ACE‐R), are essential for dementia diagnosis. We aimed to validate the use of the Korean version of ACE‐R (K‐ACER) to differentiate Alzheimer's disease (AD) from subcortical ischemic vascular dementia (SIVD). Methods: Standard tests for dementia screening were applied to 156 subjects (84 controls, 30 AD, 42 SIVD), and total and sub‐domain scores on the K‐ACER, as well as the sub‐domain ratio (VLOM), were compared. Results: The reliability of the K‐ACER was very good (α‐coefficient 0.84), and cut‐off score for dementia was determined (cut‐off value 78, sensitivity 0.93, specificity 0.95). The likelihood ratio for dementia was calculated as between 78 and 82. At a cut‐off of 78, the likelihood of dementia was 18.6:1. Although a comparison of K‐ACER scores between AD and SIVD patients revealed significant differences in verbal fluency, language domain and VLOM ratio, sensitivity and specificity for differential diagnosis between AD and SVID proved less accurate. Conclusion: The K‐ACER is a rapid, sensitive and specific dementia screening test. Though sub‐domains of items may be useful for differentiating between AD and SIVD, sensitivity and specificity is less accurate than dementia screening itself. Geriatr Gerontol Int 2010; 10: 295–301.     

血管性痴呆的扩散张量成像研究

目的应用扩散张量成像(DTI)技术,探讨皮质下缺血性血管性痴呆(SIVD)患者脑白质变化的特点及不同脑区DTI参数改变与认知的关系。方法对34例SIVD患者(SIVD组)及26例健康老年人(对照组)行DTI扫描,测量双侧前额叶、额叶深部、眶额内侧、下额叶、颞叶、顶叶、枕叶白质及T_2WI高信号区、T_2WI高信号周围正常白质区的分量各向异性(FA)、主各向异性(PA)及表观弥散系数(ADC)值。结果对照组左侧前额叶白质PA值大于右侧,ADC值小于右侧。SIVD组双侧前额叶、双侧额叶深部、下额叶、眶额内侧的FA值及PA值明显下降,平均ADC值升高;双侧顶叶的FA值下降,平均ADC值升高;双侧颞叶、枕叶平均ADC值升高;左侧下额叶、眶额内侧白质的FA与PA值较右侧小;左侧下额叶ADC值较右侧大。病变区及病变周围区的FA和PA值小于正常区,ADC值大于正常区。前额叶FA与简易智能状态检查表评分呈正相关。结论 SIVD患者脑白质FA、PA和ADC改变具有区域选择性,前部及左侧脑区损伤明显,后部及右侧相对保留白质的完整性。DTI是研究SIVD脑白质损伤的一种理想的方法。