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.     

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.     

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.     

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.     

Body mass index (BMI) at an early age and the risk of dementia

BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimer's disease (AD) (odds ratio = OR = 2.62–3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6.23–11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15–0.35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages and dementia among participants with VaD.     

Reporting of dementia on death certificates: a community study.

OBJECTIVE: To determine the extent to which conditions suggesting dementia are reported on death certificates of older adults and to identify the factors associated with reporting of dementia. DESIGN: A prospective epidemiological study in which community-dwelling subjects with and without dementia were identified and followed until death, after which their death certificates were examined. POPULATION: A total of 527 individuals who died during 8 years of follow-up of a population-based cohort of 1422 persons aged 65 and older at study entry. MEASUREMENTS: Demographic; study diagnoses, including Clinical Dementia Rating (CDR) Scale stages and diagnoses of Probable and Possible Alzheimer's disease (AD) by NINCDS-ADRDA criteria; disorders listed on death certificates as immediate, underlying, or contributory causes of death. RESULTS: Of 172 deceased subjects with study diagnoses of dementia, 30.2% had CDR = .5 and 69.8% had CDR > or = 1. Of 168 subjects in which dementia subtype could be diagnosed, Probable AD was diagnosed in 31.0% and Possible AD in 38.7%. On their death certificates, conditions indicating or suggesting dementia were reported in 23.8% of dementias overall; in 1.9% of those with CDR = .5 and 33.3% of those with CDR > or = 1; in 36.5% of those with Probable AD and 21.5% of those with Possible AD. In a multiple logistic regression model, variables associated independently with the reporting of dementia in demented individuals were: higher CDR stage of dementia (odds ratio (OR) 22.6; 95% confidence interval (CI), 2.9-174.7); likely etiology of dementia, Probable AD (OR = 3.5; CI, 1.1-10.6); and place of death, long-term care institution (OR = 3.8; 95% CI, 1.6-9.0). CONCLUSIONS: Although Alzheimer's disease is widely regarded as a leading cause of death, dementias are reported on the death certificates of only a quarter of demented individuals in the population at large. Reporting is more likely in those with more advanced dementia, with Probable Alzheimer's disease, and those who die in long-term care institutions.     

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.     

Endogenous sex hormones as risk factors for dementia in elderly men and women

BACKGROUND: The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known. METHODS: The relationship of baseline serum total estradiol (E2) and free testosterone (FT) to 4-year risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was examined in a dementia-free, population-based cohort of 433 women (mean age 74 years) and 376 men (mean age 73 years). Multivariable proportional hazards regression was used to adjust for sociodemographic and lifestyle variables, body mass index, apolipoprotein E genotype, cardiovascular conditions, and homocysteinemia. RESULTS: Dementia developed in 71 women (46 AD, 21 VaD) and 39 men (23 AD, 12 VaD). In women with high E2 (serum E2 >or= 10 pg/mL), the multivariable-adjusted hazard ratio (HR) for dementia was 1.75 (95% confidence interval [CI], 1.06-2.89). The corresponding multivariable-adjusted HR for AD was 1.94 (95% CI, 1.04-3.61), whereas no association was found for VaD. No association with dementia was found for serum FT in women and for either serum E2 or FT in men. CONCLUSION: High serum E2 is an independent predictor for dementia and AD in elderly women.     

Agreement Between Nosologist and Cardiovascular Health Study Review of Deaths: Implications of Coding Differences

OBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS). DESIGN: Observational. SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh). PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004. MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only. RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% confidence interval (CI)=0.89–0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95% CI=0.58–0.64; stroke, kappa=0.59, 95% CI=0.54–0.64; chronic obstructive pulmonary disease, kappa=0.58, 95% CI=0.51–0.65; dementia, kappa=0.40, 95% CI=0.34–0.45; and pneumonia, kappa=0.35, 95% CI=0.29–0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5%) to dementia as the underlying cause. CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause‐specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.     

Sensitivity and specificity of death certificate diagnoses for dementing illnesses, 1988-1990.

OBJECTIVE: To evaluate the extent to which mortality data, which is often used to track secular trends for specific diseases, underestimates the prevalence of dementia. DESIGN: Retrospective analysis of existing data. SETTING: Department of Mental Health inpatient facilities in South Carolina. SUBJECTS: Inpatients at Department of Mental Health facilities who were listed in the South Carolina Statewide Alzheimer's Disease and Related Disorders Registry and who died between 1988 and 1990 (n = 450). MAIN OUTCOME MEASURES: Sensitivity and specificity of dementia diagnoses on death certificates compared to medical record diagnoses for inpatients with a pre-mortem dementia diagnosis. RESULTS: Twenty-three percent of death certificates contained any dementia diagnosis (104/450). The sensitivity of death certificates varied by type of dementia (28 percent for Alzheimer's disease; 8 percent for multi-infarct dementia) as well as by race, sex, and age. CONCLUSIONS: Mortality statistics substantially underestimate the prevalence of dementing illnesses and do not fully represent the public health burden of dementia.     

Pharmacological prevention and treatment of vascular dementia: Approaches and perspectives

Vascular dementia (VaD) is a common dementing illness. There are no pharmacological agents with a regulatory approval for its treatment or prevention. Review of published clinical trial reports indicates that early treatment of hypertension, a risk factor for stroke, reduces VaD risk and slows progression. However, unlike stroke, treatment of hyperlipidemia with statin class drugs or treatment of blood clotting abnormalities with acetylsalicylic acid do not appear to have an effect on VaD incidence or progression. Pharmacological agents for treatment of Alzheimer's dementia (AD) such as memantine or acetylcholinesterase inhibitors have small positive effects on cognition in VaD, which are likely due to their action on co-existing AD-related neuropathology. Drug development efforts using novel approaches such as patient stratification by their genotype are needed in order to address the increasing need for effective VaD therapeutics.     

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.     

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.     

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.     

Causes of death for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team cohort study

BACKGROUND: To our knowledge, no previous study has systematically examined pneumonia-related and pneumonia-unrelated mortality. This study was performed to identify the cause(s) of death and to compare the timing and risk factors associated with pneumonia-related and pneumonia-unrelated mortality. METHODS: For all deaths within 90 days of presentation, a synopsis of all events preceding death was independently reviewed by 2 members of a 5-member review panel (C.M.C., D.E.S., T.J.M., W.N.K., and M.J.F.). The underlying and immediate causes of death and whether pneumonia had a major, a minor, or no apparent role in the death were determined using consensus. Death was defined as pneumonia related if pneumonia was the underlying or immediate cause of death or played a major role in the cause of death. Competing-risk Cox proportional hazards regression models were used to identify baseline characteristics associated with mortality. RESULTS: Patients (944 outpatients and 1343 inpatients) with clinical and radiographic evidence of pneumonia were enrolled, and 208 (9%) died by 90 days. The most frequent immediate causes of death were respiratory failure (38%), cardiac conditions (13%), and infectious conditions (11%); the most frequent underlying causes of death were neurological conditions (29%), malignancies (24%), and cardiac conditions (14%). Mortality was pneumonia related in 110 (53%) of the 208 deaths. Pneumonia-related deaths were 7.7 times more likely to occur within 30 days of presentation compared with pneumonia-unrelated deaths. Factors independently associated with pneumonia-related mortality were hypothermia, altered mental status, elevated serum urea nitrogen level, chronic liver disease, leukopenia, and hypoxemia. Factors independently associated with pneumonia-unrelated mortality were dementia, immunosuppression, active cancer, systolic hypotension, male sex, and multilobar pulmonary infiltrates. Increasing age and evidence of aspiration were independent predictors of both types of mortality. CONCLUSIONS: For patients with community-acquired pneumonia, only half of all deaths are attributable to their acute illness. Differences in the timing of death and risk factors for mortality suggest that future studies of community-acquired pneumonia should differentiate all-cause and pneumonia-related mortality.     

The impact of altitude on mortality from tuberculosis and pneumonia.

OBJECTIVE: To examine the association between altitude and mortality from tuberculosis (TB) and pneumonia-influenza in Mexico. DESIGN: We analysed specific causes of death in Mexico according to death certificates for the period 1993-1997, totalling over 2,700,000 deaths and including nearly 23,000 attributed to TB and 115,000 to pneumonia and influenza. Thirty population subgroups were formed based on altitude of residence (six categories) and level of poverty (five categories). The effect of altitude on mortality was estimated through Poisson regression models, with adjustment for age, gender and socioeconomic status. RESULTS: Adjusted death rates for TB decreased with altitude and increased for pneumonia-influenza. Compared to people living below 500 m above sea level, those living between 2000 and 2499 m had a 58% mortality rate for TB and a three-fold increase in mortality due to pneumonia-influenza, despite adjustment for poverty, age and gender. CONCLUSION: The mortality rate for TB based on death certificates decreases with altitude of residence, whereas the opposite is observed for pneumonia and influenza.     

Vascular dementia. Differential diagnosis and therapeutic issues

Although it has long been felt that dementia may be due to atherosclerosis, the concept has recently evolved to include multiple pathophysiological mechanisms related to deficiencies in cerebral blood supply. Epidemiological data has identified hypertension and stroke as the most potent risk factors for the development of vascular dementia (VaD). New diagnostic criteria have been proposed and new neuroimaging techniques have led to a better detection of cerebral vascular pathology. However, the differential diagnosis between Alzheimer's disease and VaD, the two most common causes of dementia, remains clinically challenging. Therapeutic interventions for VaD are limited, nevertheless several lines of evidence suggest a strong potential for preventive treatment through the control of vascular risk factors.     

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.     

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。     

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.