Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI)

MCI is regarded as a precursor of dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia (AD and VD, respectively) are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affect the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria. One-hundred-eighty elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed-up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional-hazards model adjusted for sociodemographic and medical variables. Overall conversion rate to dementia was 10.5 (8.0-13.8) per 100 person-years in the MCI group and 2.2 (1.5-3.1) per 100 person-years in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia (hazard ratio=HR=4.63, 95% confidence interval=Cl=1.72-12.46) in the MCI group, but not in the cognitively normal group (HR=1.10, 95% Cl=0.40-3.03). Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.     

Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets

Alzheimer’s disease (AD) is a neurodegenerative disorder that is multifactorial in nature. Yet, despite being the most common form of dementia in the elderly, AD’s primary cause remains unknown. As such, there is currently little to offer AD patients as the vast majority of recently tested therapies have either failed in well-controlled clinical trials or inadequately treat AD. Recently, emerging preclinical and clinical evidence has associated the brain renin angiotensin system (RAS) to AD pathology. Accordingly, various components of the brain RAS were shown to be altered in AD patients and mouse models, including the angiotensin II type 1 (AT1R), angiotensin IV receptor (AT4R), and Mas receptors. Collectively, the changes observed within the RAS have been proposed to contribute to many of the neuropathological hallmarks of AD, including the neuronal, cognitive, and vascular dysfunctions. Accumulating evidence has additionally identified antihypertensive medications targeting the RAS, particularly angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), to delay AD onset and progression. In this review, we will discuss the emergence of the RAS’s involvement in AD and highlight putative mechanisms of action underlying ARB’s beneficial effects that may explain their ability to modify the risk of developing AD or AD progression. The RAS may provide novel molecular targets for recovering memory pathways, cerebrovascular function, and other pathological landmarks of AD.

     

上海市松江区佘山镇老年人痴呆患病率调查

目的:调查上海市松江区佘山镇60岁及以上老年人的痴呆患病现状。方法:在上海市松江区的佘山镇采用横断面研究,对当地60岁及以上常住居民的痴呆患病率进行调查。以中文版简易智能状态检查量表(C-MMSE)筛查认知功能障碍,并进一步由神经科医师通过相关神经科检查及有关量表测试,参照最新推荐的国际诊断标准确定痴呆及其分型的诊断。结果:此次研究顺利完成C-MMSE初筛的研究对象共有1 472例,占有资格参加本研究总人数的71.7%;其中男666例,女806例。研究对象中被确认为认知功能障碍者167例(11.3%)。诊断为痴呆者79例,患病率为5.4%[95%可信区间(CI):4.8%～6.0%],其中诊断为阿尔茨海默病(AD)者56例(男16例,女40例),患病率为3.8%(95%CI:3.3%～4.3%),诊断为血管性痴呆(VaD)者18例(男5例,女13例),患病率为1.2%(95%CI:0.9%～1.5%)。结论:上海市松江区佘山镇老年人痴呆和AD患病率较高。     

Increased incidence of dementia following herpesvirus infection in the Korean population

Herpesviruses affect the development of dementia. We investigated the association between herpes infection and subsequent diagnoses of dementia. Data from the National Health Insurance Service of South Korea were used. Patients aged ≥50 years with the relevant diagnostic codes in the reference year 2009 were included and prospectively reviewed from January 2010 to December 2018. All study participants were followed from the index date until the onset of dementia, death, or the study endpoint. The three cohorts comprised 92,095 patients with herpes simplex virus (HSV) infections, 97,323 patients with varicella-zoster virus (VZV) infections, and 183,779 controls. During the follow-up period, 15,831 (17.19%) subjects with HSV infection and 17,082 (17.55%) VZV-infected subjects, compared to 27,028 (14.17%) control subjects, were subsequently diagnosed with dementia (all, P < .001). The adjusted hazard ratio for developing dementia was found to be 1.18 (95% confidence interval [CI]; 1.16–1.20) in HSV and 1.09 (95% CI; 1.07–1.11) in VZV patients (all, P < .001). HSV1 infections such as oral or ocular subtypes, but not HSV2, anogenital subtype, were associated with dementia, including several subtypes such as Alzheimer’s disease (AD), vascular dementia, and dementia with Lewy bodies. VZV infection is also associated with AD. In this Korean nationwide population-based cohort study, both HSV and VZV infections were associated with a higher risk of dementia, particularly AD. Among the subtypes of HSV infection, HSV1 is associated with a risk of dementia. Further studies including appropriate public health interventions could evaluate the causality of these relationships.     

Mixed dementia: a neuropathologic point od view

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in the elderly. Although AD can be diagnosed with a very high degree of accuracy, the distinction between pure AD, VaD and mixed dementia (MD), where both pathologies co-exist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. MD represents a very frequent pathology, especially in the elderly, as underlined by the neuropathological studies. However, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia and the mere existence of mixed dementia are still debated. Accurate diagnosis of MD is of crucial significance for epidemiologic purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure diseases, either AD or VaD, and have provided little data on the best therapeutic approach to MD. This review will provide an overview of neuropathological aspects of MD in the elderly, which appears to be one of the most common forms of dementia.     

痴呆240例分析

目的 对痴呆患者进行回顾性分析,提高对痴呆病种及病因的认识.方法 选择2007/2011 - 07于新疆维吾尔自治区人民医院诊断为痴呆的患者240例,其中男性145例,女性95例,均行简易型痴呆量表评定,并行CT或MRI检查诊断为痴呆.结果 240例患者最小年龄4岁,最大年龄91岁,平均年龄61.56±16.893岁.其中Alzheimer 病(AD) 69例(28％),血管性痴呆(VD) 116例(48％),路易体痴呆2例,帕金森病合并痴呆7例,正常颅压积水1例,流行性乙型脑炎1例,中枢神经系统莱姆病1例,脑肿瘤2例,贫血3例,慢性肝性脑病1例,狼疮脑病1例,慢性尿毒症脑病1例,维生素B12缺乏1例,一氧化碳中毒2例,脑外伤29例.结论 在240例痴呆患者中低龄及高龄均有发病,其中Alzheimer病(AD)、血管性痴呆(VD)比例较高,感染性疾病、代谢性或中毒性脑病、脑外伤性痴呆也占一定比例.     

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.     

Diabetes and dementia in long-term care

OBJECTIVES: To examine the presence or absence of dementia, and the prevalence rates for different dementias, in patients with and without adult onset diabetes (AODM). DESIGN: Chart survey. SETTING: A public long-term care facility in Rochester, New York, chosen to provide an enriched sample with respect to the diseases and demographic variables of interest. PARTICIPANTS: All long-term care residents in the facility aged 50 years or older (n = 476), mean age 74.8 years. Thirty-six (7.6%) had probable Alzheimer's disease (AD), 49 (10.3%) had possible AD, 38 (8.0%) had clinically diagnosed vascular dementia, 84 (17.6%) had unspecified dementias, and 269 (56.5%) were not demented. MEASUREMENTS: Demographic data, dementia and diabetes determined on the basis of extraction of chart data, and hypertension, myocardial infarction, congestive heart failure, and hypercholesterolemia determined on the basis of chart diagnoses. RESULTS: There were 99 residents with AODM in the sample, a prevalence rate of about 21%. The rates of both dementia and AODM were as expected for this age group and setting. Patients with probable or possible AD had the lowest rates of AODM (0 and 6.1%, respectively), and patients with vascular dementia had the highest rates of AODM (47.4%). Age, sex, and race influenced both the risk of having a dementia and the type of dementia. When these variables were adjusted for in multiple logistic regression, however, AODM remained a robust predictive factor because of its significant negative association with AD. Patients with unspecified dementias and no dementia showed rates of AODM (about 20%) that were roughly comparable and intermediate between vascular dementia and AD. CONCLUSIONS: In our study, AD diagnosed clinically and AODM did not co-occur, whereas AODM was associated with vascular dementia diagnosed clinically. Conversely, in non-Alzheimer, nonvascular dementias diagnosed clinically, the rates of AODM were equivalent to those in nondemented patients. These findings are in agreement with some, but not all, previous studies.     

Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.

OBJECTIVES: Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. DESIGN AND PARTICIPANTS: Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. SETTING: Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. MEASUREMENTS: Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. RESULTS: Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83% (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. CONCLUSIONS: This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based AD.     

老年期痴呆74例脑CT径线测量与神经心理测评观察

目的观察老年期痴呆患者头颅CT与神经心理测评的特点。方法通过Hackinski缺血指数表区分血管性痴呆（VD）及阿尔茨海默病（AD）,将有关的头颅CT径线和神经心理测评量表进行对比。结果①AD组和VD组头颅CT扫描各径线比较,差异具有统计学意义（P〈0.05）。②AD组和VD组简易智力状态检查表（MMSE）总分比较有统计学意义（P〈0.05）。AD和VD组与对照组比较,部分MMSE因子分差异有统计学意义（P〈0.05或P〈0.01）。③AD组和VD组小脑沟条数差异具有统计学意义（P〈0.05）。结论 AD组大脑萎缩及痴呆程度重于VD组,而小脑萎缩则不尽然。结合CT检查和神经心理测评仍是鉴别VD及AD的有效方法 。     

Incidence of Alzheimer's dementia in homes for the elderly

This study tried to emphasize the significance of statistical data (incidence rate) considering Alzheimer dementia (AD) because variations in incidence and types of dementias do exist in different countries. The data of persons living in two homes (elderly people and psychiatric patients) were overviewed together with the patients admitted to our hospital in 1993. It was discovered that there were 40 Alzheimer dementia cases in our catchment area of 107,000 population which may be increased by private and undiscovered cases to approximately 50 cases. The number of the vascular dementia (VD) proved to be higher (2-3 x) than the AD. Our findings need also explanation considering the different proportions in the incidence rate of Alzheimer and vascular dementia existing between Hungary and other countries. It was concluded that the lower life expectancy, a tendency for vascular diseases and some environmental factors may be responsible for the higher number of VD. However these findings and statements should not decrease our effort in the research work which has to include the study of the etiology, pathogenesis and the possibility of a successful treatment of AD in the future.     

Mixed dementia: epidemiology,diagnosis, and treatment

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in older people. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD, and mixed dementia (MD), where both pathologies coexist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. Although MD represents a very frequent pathology, especially in older people, as reported in neuropathological studies, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia, and the mere existence of MD are still debated. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, AD or VaD, and have provided little information on the best therapeutic approach to MD. This article provides an overview of MD in older people. A retrospective review of the recent literature on prevalence, incidence, course, risk factors, diagnosis, and treatment of MD was performed. The article also emphasizes the need for further studies, including neuropsychological and functional evaluations, and neuroimaging and clinicopathological correlations to develop a better understanding of MD, which appears to be one of the most common forms of dementia.     

西安地区中老年人的痴呆患病率调查

目的：了解西安载我中老年人痴呆的流行现状。方法：E要用多分层,多级,随机、整群抽样、以简易智能状态量表（MMSE）为筛查工具,对西安地区4850例5及以上中老年人进行了痴呆患病率调查。结果：符合美国精神疾病诊断和统计手册第4版（DSM－Ⅳ）和美国国立神经病学、语言交流障碍和卒中－老年性痴呆 关疾病学会（NINCDS－ADRDA）痴呆诊断标准者171例,痴呆患病率3．53％。其中Alzheimer痴呆（AD）100例,患病率2．06％,占58．48％,血管性痴呆（VD）54例,患病率1．11％,占31．58％,痴呆及VD患病率男女间差异无显著性P＞0．05）,而AD患病率女性明显高于男性（P＜0．01）。痴呆及AD、VD、患病率均随增龄而显著增高（P＜0．01）,年龄每增长5岁,患病率约增高1倍。文盲组痴呆及AD患病率高于小学和初中以上组（P＜0．01）。各职业之间痴呆及AD、VD患病率用年龄分层后差异均无显著性（P＞005）。城市和农村痴呆、AD、VD患病率差异亦无显著性（P＞0．05）。结论：我国痴呆患病率并不低,基本与欧美国家持平,高龄、女性、低文化水平,能是AD的危险因素。     

Incidence and risk factors of dementia and the primary subtypes in northern rural China

This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.     

A neuropathological study of dementia in nursing homes in Shimane prefecture, Japan: evaluation of the age and gender effect.

BACKGROUND: Vascular dementia (VD) has been held responsible for the majority of all dementia cases in both epidemiological and neuropathological studies in Japan. The aim of this study was to clarify relative frequencies of dementia neuropathologically in Japanese nursing home residents over a 17-year period and to clarify the gender and age effect on the relative frequencies. METHODS: Three hundred ten aged nursing home residents (146 men and 164 women), including dementia cases in Shimane prefecture, Japan, were evaluated clinically and neuropathologically over a period of 17 years. RESULTS: One hundred twenty-two (48 men and 74 women) of the 310 autopsied (39%) had shown signs of dementia during their lives. In classifying dementia type, Alzheimer's disease (AD) accounted for 34% (41); VD 35% (42); mixed dementia 11% (14); and "other" dementia 20% (25) of all samples. As to the gender and age effect, the most characteristic findings were as follows: (a) There were only VD cases in the 57-69-year-old group; (b) the 70-79 male age group lacked any cases with only AD; (c) more AD than VD was found in elderly men; and (d) in women, AD was the major cause of dementia in total. CONCLUSIONS: VD is responsible for the major cause of dementia in the younger women and the men under 90 years of age; AD is the leading cause of dementia in the elderly men and the women over 79 years of age in nursing homes, Shimane prefecture, Japan.     

Functional performance of Alzheimer's disease and vascular dementia in southern Taiwan

This study investigated the functional performance of two major subtypes of dementia, Alzheimer's disease (AD) and vascular dementia (VaD), by the Functional Independence Measure (FIM), and to understand the need for assistance in performing activities of daily living. The subjects comprised 64 AD and 21 VaD patients who were recruited from two epidemiologic studies of dementia with a total of 3,931 community residents aged 65 years and above in southern Taiwan. The results showed that the severity of dementia was similar between the two groups. The mean score for AD was 82.7 and for VaD was 56.5 for total FIM (p < 0.05), 61.6 and 41.7 for the motor dimension (p < 0.05), and 21.1 and 15.7 for the cognitive dimension (p < 0.05). There were significant differences (p < 0.01) between AD and VaD in six FIM items and borderline or marginal significance (p < 0.05) in most of the FIM items. For AD patients, stairs, lower dressing, bathing, and tub/shower transfer were the most difficult items in the motor dimension, and it was memory in the cognitive dimension. For VaD patients, bathing, upper and lower dressing, and grooming were the most difficult items in the motor dimension, and it was problem solving in the cognitive dimension. VaD patients were more dependent on all FIM items and required more assistance than AD patients. The functional performances of dementia patients were significantly associated with dementia severity and subtypes, together accounting for 40% of the variability in total FIM. In conclusion, most dementia patients are dependent in daily activities and different types and severity of dementia lead to different disability profiles; individualized care is, therefore, most appropriate.     

Analyses of serum concentrations of apolipoproteins in the demented elderly

OBJECTIVE: The aim was to analyze serum concentrations of apolipoproteins in the demented elderly to elucidate some biological markers related to dementia. PATIENTS AND METHODS: Serum concentrations of apolipoproteins (AI, AII, B, CII, CIII, E) of patients with Alzheimer type dementia (AD), vascular dementia (VD) and controls (C) without dementia were compared among the three groups (AD, VD, C) and 15 correlation coefficients among the 6 measured items of apolipoproteins were analyzed. RESULTS: Serum levels of apo CII were significantly lower in AD group compared with VD or C groups. Serum levels of apo B, CIII and E were significantly lower in AD group compared with VD group, but not with C group. Analyses of correlations among the items of apolipoproteins revealed high significant correlations between apo E and/or apo CII and other items in AD group. CONCLUSION: These results suggest that apolipoproteins such as apo CII, as well as apo E, might be involved in the pathogenesis of AD.     

尿酸对认知功能的影响

阿尔茨海默病和帕金森病是老年人常见的神经退行性疾病。认知功能障碍是阿尔茨海默病的主要临床表现,帕金森病在发展过程中,尤其到疾病晚期,可合并有痴呆表现,称帕金森病痴呆。不同的调查研究显示,帕金森病患者中有17％～57％会伴发认知功能障碍。研究影响认知功能的相关因素对于防治阿尔茨海默病,提高帕金森病患者的生活质量具有重要的意义。近年来发现,血尿酸水平与认知功能密切相关。     

Cerebrovascular disease in the elderly: lipoprotein metabolism and cognitive decline

Data concerning the treatment of lipoprotein disturbances in patients with cerebrovascular disease (CVD) are less robust than those for coronary heart disease (CHD), raising clinical questions as to which is the appropriate therapeutic approach to stroke patients. Although observational cohort studies have failed to demonstrate an association between lipoprotein disorders and stroke incidence, recently completed trials of subjects at risk for CHD have shown that statins reduce not only the risk of myocardial infarction and death, but also that of brain infarction and transient ischemic attacks. At present, it seems reasonable to conclude that stroke patients with undesirable lipid profiles who have a history of CHD should receive specific treatment for the lipid disorder. Recommendations are more problematic for stroke patients with lipid disorder but no history of CHD. Furthermore, many of the risk factors for CVD and vascular dementia (VaD), including serum total cholesterol (TC), lipoprotein(a), diabetes, atrial fibrillation, hypertension, apolipoprotein E levels, and atherosclerosis, have also been shown to increase the risk of Alzheimer's disease (AD). In a recent study, we estimated the prevalence, incidence and rate of progression of Mild Cognitive Impairment (MCI) to dementia, and correlated vascular risk factors with incident MCI and its progression to dementia. We evaluated 2963 individuals from the population-based sample of 5632 subjects 65-84 years old of the Italian Longitudinal Study on Aging, with a 3.5-year follow-up. We found a progression rate to dementia (all causes) of 3.8/100 person-years. Furthermore, age was a risk factor for incident MCI, while education was protective, and serum TC evidenced a non-significant borderline trend for a protective effect. There was a non-significant trend for stroke as a risk factor of progression of MCI to dementia. In conclusion, in our population, among MCI patients who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors and CVD may influence the development of MCI and the rate of progression to dementia.