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.     

血管性痴呆的临床诊断和治疗

近年来,血管性痴呆(VaD)的定义和临床诊断标准逐渐建立。已有2个很好的工具可用于VaD的诊断———NINDS-AIREN和ADDTC。尽管NINDS-AIREN和NINCDS-ADRDA标准可用来区分单纯性VaD和单纯性Alzheimer病,但VaD与Alzheimer病的鉴别以及混合性痴呆的诊断仍然具有一定的挑战性。一系列研究已证实乙酰胆碱酯酶抑制剂治疗VaD的作用,它不但能改善认知功能,而且还对脑功能恢复也有一定的益处。     

Vascular Dementia: Distinguishing Characteristics, Treatment, and Prevention

Vascular dementia (VaD) is the second-most-common cause of dementia in the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and hyperhomocysteinemia.     

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.     

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.     

Lipids' peroxidation markers in Alzheimer's disease and vascular dementia

Aim: Although a large body of evidence supports a role of oxidative stress in the etiopathogenesis of dementia, there is still a substantial lack of data regarding the biomarkers of oxidative stress characteristic of Alzheimer's disease (AD) as opposed to different types of dementia. In this study, the level of various oxidative stress parameters were measured in AD, vascular dementia (VaD), and age‐ and sex‐matched control patients. The AD and VaD patients all had similar levels of cognitive impairment as measured by the Mini‐Mental State Examination. Methods: Thirty AD, 19 VaD and 29 controls patients were recruited to the study. Plasma levels of malondialdehyde (MDA), total sulfhydryl (T‐SH), calcium (Ca⁺⁺) and magnesium (Mg⁺⁺) were measured. Results: In both AD and VaD groups, the levels of oxidative stress parameters were higher compared with controls. Further, the VaD patients expressed significantly higher levels of plasma parameters of oxidative stress than AD. The difference was noted in MDA, the marker of lipid peroxidation, whereas in VaD the level of MDA was more than 2.8‐fold higher than that registered in AD patients. Conclusion: Vascular dementia in patients is characteristic of increased levels of oxidative stress, especially lipid peroxidation markers. This finding is relevant to determining the pathophysiology of dementia, particularly in the light of the recently suggested importance of the vascular component in dementia development, in addition to aiding in the diagnosis of VaD following clinical presentation. The study will be continued to compare the character and level of decline in both groups.     

Mild cognitive impairment subtypes and vascular dementia in community-dwelling elderly people: a 3-year follow-up study

OBJECTIVES: To investigate whether mild cognitive impairment (MCI) with multiple impaired cognitive domains (mcd-MCI) is a prodromal manifestation of vascular dementia (VaD). DESIGN: Prospective cohort study. SETTING: Geriatric unit of the Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. PARTICIPANTS: Four hundred community-dwelling subjects aged 65 and older who came freely to the geriatric unit as part of a comprehensive geriatric assessment program were evaluated for memory impairment or other cognitive disorders. Subjects with MCI were kept under observation for 3 years. MEASUREMENTS: Subjects with MCI were studied by applying a standardized clinical evaluation and a conducting a computed tomography brain scan. Cognitive performance was assessed using the Mini-Mental State Examination, the Clock Drawing Test, and a comprehensive battery of neuropsychological tests. Cardiovascular comorbidity was assessed on the basis of medical history and using electrocardiography, echocardiography, and carotid color Doppler ultrasound. RESULTS: MCI was found in 65 of the 400 community-dwelling subjects; 31 were classified with amnestic MCI (a-MCI) and 34 with mcd-MCI. A dysexecutive syndrome characterized people with mcd-MCI, who had significantly more vascular comorbidity and signs of vascular disease on brain imaging as well as a higher prevalence of extra pyramidal features, mood disorders, and behavioral symptoms than people with a-MCI. Twenty of the 65 subjects with MCI (31%) progressed to dementia within 3 years of follow-up: 11 subjects with Alzheimer's disease (AD) and nine with VaD. All patients who evolved to AD had been classified with a-MCI at baseline, whereas all patients who evolved to subcortical VaD had been classified with mcd-MCI at baseline. CONCLUSION: All subjects who converted to subcortical VaD had been classified with mcd-MCI, suggesting that mcd-MCI might be an early stage of subcortical VaD.     

Metabolic Syndrome and Risk of Dementia in Older Adults

OBJECTIVES: To investigate the association between metabolic syndrome (MetS; a clustering of cardiovascular risk factors including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, each of which has been individually associated with dementia) and incident dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older adults before and after the age of 75. DESIGN: Prospective population‐based cohort. SETTING: An Italian municipality. PARTICIPANTS: A community‐based sample of 749 subjects aged 65 and older who, in 1999/2000, were free of cognitive impairment and, in 2003/04, underwent follow‐up for incident dementia. MEASUREMENTS: The relationship between incident overall dementia, AD, and VaD and MetS. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. MetS was defined according to the National Cholesterol Education Program criteria. RESULTS: Risk of overall dementia and its subtypes was not associated with MetS or any MetS component in participants younger than 75. In participants aged 75 and older, MetS was associated with a lower risk of AD (hazard ratio (HR)=0.33, 95% confidence interval (CI)=0.12–0.94) but not of VaD, and abdominal obesity was associated with a lower risk of overall dementia (HR=0.53, 95% CI=0.28–0.98). CONCLUSION: MetS measured in late life is not associated with risk of dementia. After age 75, persons with MetS may even be at lower risk for AD.     

Comparison of vascular stiffness in vascular dementia, Alzheimer dementia and cognitive impairment

Abstract Defining the vascular component(s) of the clinical diagnosis of vascular cognitive impairment (VCI) and vascular dementia (VaD) continues to be problematic. The goal of this study was to determine whether vascular stiffness, measured by pulse wave velocity (PWV), is altered in VaD, to study the utility of PWV in differentiating VaD from Alzheimer dementia (AD) and the relationship between PWV and cognitive function. A qualitative and quantitative structured analysis of the literature was conducted until September 2010, using a search strategy based on the key words: dementia, vascular dementia, dementia of vascular origin, cognitive function and arterial stiffness or pulse wave velocity. Seventeen studies assessed large vessel vascular stiff by PWV and related it to cognitive function or dementia. Six of these studies compared PWV in 154 persons with VaD, 207 with AD and 197 controls without dementia. Mean PWV was significantly (p < 0.0001) higher in VaD compared with controls. Mean PWV was significantly (p = 0.002) higher in VaD compared with AD. Fourteen studies examined the relationship between PWV and cognitive function. The majority of studies (nine of 14) reported a significant correlation between PWV and cognitive function. Four of eight studies that evaluated the relation using univariate analysis reported a significant correlation of PWV with the Mini Mental State Exam (MMSE) or Hasegawa Dementia Scale, and the correlation with MMSE between studies showed a close agreement of correlation coefficients (0.206 to 0.27). In multivariate analysis, adjusted for a wide range of possible confounding factors, the majority or 80% (eight out of 10) studies comprising a population of 6,034 individuals found a significant inverse relationship between PWV and cognitive function. In summary, vascular stiffness is inversely related to cognitive function. Vascular stiffness is greater in VaD compared with AD, suggesting PWV may be useful in identifying VaD.     

Prevalence and severity of gait disorders in Alzheimer's and non-Alzheimer's dementias

OBJECTIVES: To compare the prevalence, severity, and type of gait and balance disorders in Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), Parkinson's disease without dementia (PD), and age-matched controls. DESIGN: Cross-sectional. SETTING: Secondary care clinics in geriatric psychiatry, neurology, and geriatrics. PARTICIPANTS: Two hundred forty-five participants aged 65 and older (AD, n=40; VaD, n=39; PDD, n=46; DLB, n=32; PD, n=46; and controls, n=42). MEASUREMENTS: Prevalence and severity of gait and balance disorders were assessed using the Tinetti gait and balance scale. The types of gait disorders in each diagnostic group were classified using the Nutt et al. classification. RESULTS: Gait and balance disorders were more common with PDD (93%), VaD (79%), and DLB (75%) than with PD (43%) and AD (25%) and in controls (7%). The risk of gait and balance disorder was higher in the non-Alzheimer's dementia groups (VaD, PDD, and DLB) than in the AD group (odds ratio=15 (95% confidence interval=6-37). If a gait disorder was present in mild dementia (Cambridge Examination for Mental Disorders of the Elderly cognitive subsection score >65), this was diagnostic of non-Alzheimer's dementia, with sensitivity of 78% and specificity of 100%. Non-Alzheimer's dementia groups had worse Tinetti gait and balance scores than the AD group (all P<.001). The types of gait disorders discriminated between non-Alzheimer's dementias. CONCLUSION: The findings support the idea that gait and balance assessment may augment the diagnostic evaluation of dementia.     

Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study

OBJECTIVES: To investigate the association between midlife risk factors and the development of vascular dementia (VaD) or Alzheimer's disease (AD) 25 to 30 years later. DESIGN: A prevalence study within a longitudinal cohort study. SETTING: Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan. PARTICIPANTS: One thousand seven hundred seventy-four subjects in Hiroshima, Japan born before September 1932 (1,660 with no dementia, 114 with dementia (51 with AD, and 38 with VaD) diagnosed from 1992 to 1997 according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). MEASUREMENTS: The subjects were examined for effect on dementia of sex, age, education, atomic bomb radiation dose, and midlife factors associated with risk (smoking, alcohol intake, physical activity, dietary habits, systolic blood pressure (SBP), body mass index, and history of diabetes mellitus) that had been evaluated in 1965-1970. RESULTS: VaD prevalence increased significantly with age, higher SBP, and lower milk intake. The odds ratios of VaD for age (in 5-year increments), SBP (10 mmHg increments), and milk intake (almost daily/less than four times a week) were 1.29, 1.33, and 0.35, respectively. The risk factors for VaD were compatible with the risk factors for stroke in this study population. AD prevalence increased significantly with age and lower education. Other midlife factors and radiation dose did not show any significant association with VaD or AD. CONCLUSION: Increased SBP and low milk intake in midlife were associated with VaD detected 25 to 30 years later. Early behavioral control of the risk factors for vascular disease might reduce the risk of dementia.     

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.     

Comparisons of cognitive deterioration rates by dementia subtype

Pathophysiological aspects of dementia and its rate of cognitive deterioration could be dependent on disease subtype, Alzheimer's dementia (AD), vascular dementia (VaD), and Parkinson's disease with dementia (PDD). 150 patients diagnosed at the Chungnam National University Hospital (87 women and 63 men) memory clinic. The participants consisted of 68 patients with AD, 23 patients with VaD, and 59 patients with PDD, who were diagnosed by the individual criteria, respectively. Cognitive screening was evaluated using the Korean version of the mini-mental state examination (MMSE). Repeated evaluations were conducted at 6-month, 1 year, and 2 years after initial baseline assessment. Rates of cognitive decline were calculated by dividing MMSE score differences by the number of months lapsed. No difference was found between the three dementia subtypes with respect to baseline MMSE scores. Cognitive decline was not obvious up to 6-month of the follow-up, but by 12-month of follow-ups was significant regardless of the dementia subtype. Furthermore, the rate of cognitive decline in the AD group was significantly faster than in the PDD or VaD groups. This study suggests that rate of cognitive deterioration in dementia is not linear over time and that dementia subtypes have different rates of cognitive deterioration.     

Relationship between serum insulin-like growth factor-1 levels and Alzheimer's disease and vascular dementia

OBJECTIVES: To determine whether decreased serum insulin-like growth factor-1 (IGF-1) levels could be a risk factor for dementia in older people. DESIGN: Case control study. SETTING: Showa University Karasuyama Hospital, Tokyo, Japan. PARTICIPANTS: A total of 436 Japanese elderly subjects: 106 patients with Alzheimer's disease (AD), 103 patients with vascular dementia (VaD), and 227 age-matched controls without dementia. MEASUREMENTS: Serum concentrations of IGF-1 and atherogenic lipoproteins, carotid artery intima-media thickness (IMT), and plaques were determined. RESULTS: Mini-Mental State Examination (MMSE) scores were positively correlated with serum IGF-1 concentrations as well as mean blood pressure or body mass index and were negatively correlated with age, serum low-density lipoprotein cholesterol and lipoprotein(a) concentrations, and carotid IMT. Serum IGF-1 concentrations had a significant inverse correlation with carotid IMT. Analysis across the IGF-1 quartiles revealed a threshold effect of low IGF-1 on MMSE score in subjects with the IGF-1 levels of 140 ng/mL or less (50% percentile) versus those with IGF-1 levels greater than 140 ng/mL. Multiple logistic regression concerning AD and VaD retained serum IGF-1 concentrations of 140 ng/mL or less and carotid IMT of 0.9 mm or more. Patients with AD and VaD had significantly lower IGF-1 concentrations and greater mean IMT than nondemented controls. CONCLUSION: These results suggest that decreased serum IGF-1 level and the progression of carotid atherosclerosis could play a role as independent risk factors for dementia.     

Different changes of bone mineral density and nutritional status after hospitalization between vascular dementia and Alzheimer's disease in elderly female patients

Background:   Bone fractures strongly influence morbidity and mortality in elderly patients with dementia. The goal of this study was to examine whether difference in the type of dementia affects changes of bone mineral density (BMD) during hospitalization with rehabilitation programs.
Methods:   Ninety-four Japanese elderly female patients were enrolled. BMD, Mini-Mental State Examination (MMSE) scores, and levels of serum albumin, calcium-related factors and urinary calcium excretion were measured.
Results:   Multivariable analyses indicated that serum albumin levels and MMSE scores were positively correlated with changes in BMD after 2 years hospitalization. Significant reduction of BMD levels after hospitalization were observed in patients with severe dementia (MMSE scores, <10) or with severe malnutrition (serum albumin, <2.0). We next classified our subjects into three groups according to the 4th edn of the Diagnostic and Statistical Manual criteria: non-dementia (ND), Alzheimer's disease (AD) and vascular dementia (VaD). Although there were no significant differences in age and physical activities among the groups; the levels of BMD were maintained in AD as well as ND but not in VaD. Notably, calcium excretion levels were significantly decreased after hospitalization in AD as well as ND but not in VaD. Serum 25(OH)D levels were also restored in AD but not in VaD. In addition, the nutritional status significantly improved in AD but not in VaD.
Conclusion:   The levels of BMD were maintained and the nutritional status was improved in AD but not in VaD for 2 years hospitalization with rehabilitation programs. These results suggest that different programs including nutritional support may be necessary for maintaining BMD levels in VaD as compared with AD during hospitalization.     

Helicobacter pylori and Alzheimer's disease: a possible link

BACKGROUND: Although serological findings indicate the presence of a relationship between Helicobacter pylori (HP) and vascular disease, no data have been reported about a possible association of HP with dementia. The aim of the present study was to determine whether chronic HP infection might play a role in Alzheimer's disease (AD). METHODS: Plasma homocysteine level, serum folate and vitamin B(12) concentrations, plasma pyridoxal phosphate level, IgG and IgA antibodies to HP, and C-reactive protein (CRP) were determined in 30 AD patients, 30 patients affected by vascular dementia (VaD), and 30 control subjects. All patients and control subjects were matched for age, educational level, and nutritional and socioeconomic status. None of the subjects had a history of chronic gastritis, peptic ulcer, gastric cancer, or major abdominal surgery. RESULTS: HP-IgG level was significantly increased in VaD patients as compared to controls and AD patients, while AD patients had HP-IgG levels higher than those of normal controls. HP-IgA levels were equally increased in both VaD and AD patients. CRP was higher in AD patients than in VaD patients and controls, although CRP levels in VaD patients were also significantly increased. CONCLUSIONS: The present study found an association between HP infection and AD. The question remains as to whether this association is due to the ubiquity of HP, or whether it contributes to the neuroinflammatory process in AD. The relationship between HP and AD, if confirmed by additional studies with a greater number of patients, may have important clinical and therapeutic implications.     

Quantitative electroencephalography, with serial subtraction and odour detection in the differentiation of Alzheimer's disease and vascular dementia

The diagnosis of dementia can be difficult, yet diagnostic accuracy has important prognostic and therapeutic implications. Nevertheless, conventional electroencephalography (EEG) has always played a secondary role in dementia investigation. More recently quantitative EEG (qEEG) has allowed more detailed and objective analysis of EEG data, but there is still no clearly defined clinical role for qEEG. We have used relative power qEEG measures made during resting and active brain conditions (serial subtraction and odour detection tasks) to differentiate between demented and non-demented subjects, and between subjects with different forms of dementia. Electroencephalograms were obtained from 15 subjects with clinically diagnosed Alzheimer's disease (AD), 16 with a clinical diagnosis of vascular dementia (VaD), and 16 non-demented control subjects. Discriminate function analyses were used to differentiate groups according to task, electrode site, and frequency bandwidth. Correct classification, as demented or non-demented, was made for 93% of cases using qEEG comparisons of resting states with eyes closed and eyes opened. Almost all subjects with AD and VaD were correctly classified with qEEG recorded during odour detection (95%). qEEG for serial subtraction correctly classified AD and VaD in 91% of the dementia group. These results have important implications for future qEEG research, and may be pertinent to the precision of diagnosis in patients with dementia.     

Toll样受体4在阿尔茨海默病及血管性痴呆患者外周血单核细胞表达的初步研究

目的:检测Toll样受体4(TLR4)在阿尔茨海默病(AD)及血管性痴呆(VaD)患者外周血单核细胞的表达情况,探讨TLR4在老年期痴呆发病机制中的可能作用。方法:选择临床确诊的AD患者(n=26)、VaD患者(n=31)和正常对照组(n=29)共86例,采用流式细胞术检测3组外周血单核细胞膜上TLR4蛋白阳性表达率及平均荧光强度(MFI)并进行比较分析。结果:外周血单核细胞膜表达TLR4的阳性表达率和MFI AD组和VaD组较对照组明显增高(P0.05)。结论:TLR4作为免疫炎性机制信号通路的关键蛋白,在AD、VaD的发病中均表现为增高,提示炎性机制在AD和VaD的发病中均发挥了作用,TLR4可能不能作为鉴别诊断的潜在生物标志物。     

血管性痴呆的神经生化机制

由于血管性痴呆的发病率逐年上升,且较Alzheimer病有更高的防治价值,因此对其发病机制的研究具有非常重要的医学和社会意义。研究表明,乙酰胆碱、单胺类物质、兴奋性氨基酸等神经递质,生长抑素、血管活性物质等神经肽,自由基以及某些激素均参与了学习记忆过程,并可能在血管性痴呆的发生和发展中发挥重要作用。     

Epidemiology of vascular dementia.

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer's disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.