Heterogeneous Disease Progression in a Mouse Model of Vascular Cognitive Impairment.

Recently, an asymmetric vascular compromise approach that replicates many aspects of human vascular cognitive impairment (VCI) has been reported. The present study aimed to first investigate on the reproducibility in the disease progression of this newly reported VCI model using wild-type C57BL6/J mice. The second aim was to assess how this approach will affect the disease progression of transgenic Alzheimer's disease (AD) 5XFAD mice subjected to VCI. C57BL6/J and 5XFAD mice were subjected to VCI by placing an ameroid constrictor on the right CCA and a microcoil on the left CCA. Infarcts and hippocampal neuronal loss did not appear predominantly in the right (ameroid side) as expected but randomly in both hemispheres. The mortality rate of C57BL6/J mice was unexpectedly high. Inducing VCI reduced amyloid burden in the hippocampi of 5XFAD mice. Since VCI is known to be complex and complicated, the heterogeneous disease progression observed from this current study shares close resemblance to the clinical manifestation of VCI. This heterogeneity, however, makes it challenging to test novel treatment options using this model. Further study is warranted to tackle the heterogeneous nature of VCI.

Survival and life-expectancy in a young-onset dementia cohort with six years of follow-up: the NeedYD-study.

OBJECTIVES: The aim of this study was to investigate survival time and life-expectancy in people with young-onset dementia (YOD) and to examine the relationship with age, sex, dementia subtype and comorbidity. DESIGN, SETTING AND PARTICIPANTS: Survival was examined in 198 participants in the Needs in Young-onset Dementia study, including participants with Alzheimer's dementia (AD), vascular dementia (VaD) and frontotemporal dementia (FTD). MEASURES: The primary outcomes were survival time after symptom onset and after date of diagnosis. Cox proportional hazards models were used to explore the relationship between survival and age, sex, dementia subtype and comorbidity. Additionally, the impact on remaining life expectancy was explored. RESULTS: During the six-year follow-up, 77 of the participants died (38.9%), 78 participants survived (39.4%) and 43 were lost to follow-up (21.7%). The mean survival time after symptom onset and diagnosis was 209 months (95% CI 185-233) and 120 months (95% CI 110-130) respectively. Participants with AD had a statistically significant shorter survival compared with VaD participants, both regarding survival after symptom onset (p = 0.047) as well as regarding survival after diagnosis (p = 0.049). Younger age at symptom onset or at diagnosis was associated with longer survival times. The remaining life expectancy, after diagnosis, was reduced with 51% for males and 59% for females compared to the life expectancy of the general population in the same age groups. CONCLUSION/IMPLICATIONS: It is important to consider the dementia subtype when persons with YOD and their families are informed about the prognosis of survival. Our study suggests longer survival times compared to other studies on YOD, and survival is prolonged compared to studies on LOD. Younger age at symptom onset or at diagnosis was positively related to survival but diagnosis at younger ages, nevertheless, still diminishes life expectancy dramatically.

Incident depression and mortality among people with different types of dementia: results from a longitudinal cohort study.

PURPOSE: The aim of this study was to investigate the independent and combined association of incident depression and dementia with mortality and to explore whether the magnitude of the association varies according to different types of dementia, including Alzheimer's disease and vascular dementia. METHODS AND DESIGN: The study was based on a population-based longitudinal cohort consisting of 9940 participants at baseline and followed for over 14 years. The sample used for the analyses included 6114 participants with available information on diagnosis of incident dementia and depression. For survival analyses, Cox regression models with incident dementia (n = 293; 5%) and incident depression (n = 746; 12%) as time-dependent variables were used. RESULTS: Cox models adjusted for relevant confounders indicated that comorbidity of incident vascular dementia and incident depression was associated with a much higher mortality risk (HR 6.99; 95% CI 3.84-12.75) than vascular dementia in the absence of depression (HR 2.80; 95% CI 1.92-4.08). In contrast, estimates for comorbidity of Alzheimer's disease and depression were slightly lower than those for Alzheimer in absence of depression (HR 3.56; 95% CI 1.83-6.92 and HR 4.19; 95% CI 2.97-5.90, respectively). Incident depression in the absence of incident dementia was only weakly associated with mortality. CONCLUSIONS: These findings indicate that depression and vascular dementia might have synergistic effects on mortality. The results have relevant public health implications for prevention, routine screening for and early treatment of depression among older people, especially those at risk of vascular dementia.

Tube feeding decreases pneumonia rate in patients with severe dementia: comparison between pre- and post-intervention.

BACKGROUND: It is widely supposed that there is no benefit, including extended survival and decreased rate of pneumonia, in patients with severe dementia receiving enteral tube feeding (TF). However, there have been few studies comparing the frequency of pneumonia before and after TF in severe dementia. METHODS: Nine psychiatric hospitals in Okayama Prefecture participated in this retrospective survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty in oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition, and they decided whether or not to make use of long-term artificial nutrition from January 1, 2014 to December 31, 2014. RESULTS: We evaluated 58 patients including 46 with TF and 12 without. The mean age of all patients was 79.6 ± 9.0 years old. Patients with probable Alzheimer's disease (n = 38) formed the biggest group, and those with vascular dementia the second (n = 14). Median survival times were 23 months among patients with TF and two months among patients without TF. The start of TF decreased the frequency of pneumonia and the use of intravenous antibiotics. CONCLUSIONS: TF decreased pneumonia and antibiotic use, even in patients with severe dementia. The results of this study do not necessarily indicate that we should administer TF to patients with severe dementia. We should consider the quality of life of patients carefully before deciding the use or disuse of TF for patients with severe dementia.

Reporting of clinically diagnosed dementia on death certificates: retrospective cohort study.

BACKGROUND: mortality statistics are a frequently used source of information on deaths in dementia but are limited by concerns over accuracy. OBJECTIVE: to investigate the frequency with which clinically diagnosed dementia is recorded on death certificates, including predictive factors. METHODS: a retrospective cohort study assembled using a large mental healthcare database in South London, linked to Office for National Statistics mortality data. People with a clinical diagnosis of dementia, aged 65 or older, who died between 2006 and 2013 were included. The main outcome was death certificate recording of dementia. RESULTS: in total, 7,115 people were identified. Dementia was recorded on 3,815 (53.6%) death certificates. Frequency of dementia recording increased from 39.9% (2006) to 63.0% (2013) (odds ratio (OR) per year increment 1.11, 95% CI 1.07-1.15). Recording of dementia was more likely if people were older (OR per year increment 1.02, 95% CI 1.01-1.03), and for those who died in care homes (OR 1.89, 95% CI 1.50-2.40) or hospitals (OR 1.14, 95% CI 1.03-1.46) compared with home, and less likely for people with less severe cognitive impairment (OR 0.95, 95% CI 0.94-0.96), and if the diagnosis was Lewy body (OR 0.30, 95% CI 0.15-0.62) or vascular dementia (OR 0.79, 95% CI 0.68-0.93) compared with Alzheimer's disease. CONCLUSIONS: changes in certification practices may have contributed to the rise in recorded prevalence of dementia from mortality data. However, mortality data still considerably underestimate the population burden of dementia. Potential biases affecting recording of dementia need to be taken into account when interpreting mortality data.

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and vascular dementia.

BACKGROUND: Pneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated. METHODS: We retrospectively analyzed the data from medical and autopsy reports. All study patients had been hospitalized and underwent brain autopsy in a hospital in Toyohashi, Japan, between 2005 and 2014. The patients with subtypes of dementia, specifically Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), were neuropathologically diagnosed and examined. Pneumonia incidence, cause of death, and the clinical time-course of dementia were compared among the dementia subtypes. The time to death from dementia onset (survival time) was compared by the Kaplan-Meier method among subtypes of dementia with or without pneumonia. Risk factors for survival time on all study patients were analyzed with the Cox proportional hazard model. RESULTS: Of the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan-Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD. CONCLUSIONS: Pneumonia complications shortened the survival time of patients with AD, DLB, and VaD.

Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population.

BACKGROUND: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. METHODS: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. RESULTS: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. CONCLUSIONS: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study.

OBJECTIVES: People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs. METHODS: A clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality. RESULTS: Patients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87-1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59-1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93-1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results. CONCLUSIONS: The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD.

The natural history of dementia.

This review summarizes studies on the natural history of dementia with a focus on Alzheimer's disease and vascular dementia. Understanding the course of dementia is important not only for patients, caregivers, and health professionals, but also for health policy-makers, who have to plan for national resources needed in the management of an increasing number of dementia cases. From the available published data, the life expectancy of elderly people with dementia is shorter than that of non-demented elderly. Reports on survival after a diagnosis of dementia vary from 3 to 12 years. The wide variation is partly due to the diagnostic criteria used in the studies and the sites where they were conducted (i.e. hospitals, clinics, or homes). There is an apparent difference in survival between Alzheimer's disease patients with onset of illness before 75 years and those after 75 years: the younger patients have a longer life expectancy. However, there are conflicting data on survival (in years) comparing male and female patients and comparing patients of different ethnicities. For vascular dementia, published papers on life expectancy vary between 3 to 5 years. Vascular dementia appears to have a poorer prognosis than Alzheimer's disease. The stages of severity of dementia were compared in a follow-up of a sample of Alzheimer's disease patients in Singapore, and the mean duration of the mild phase (clinical dementia rating 1) was 5.6 years, the moderate phase (clinical dementia rating 2) was 3.5 years, and the severe phase (clinical dementia rating 3) was 3.2 years. At the various phases of the disease, the demand on health-care services and economic cost are different.

Evaluating the prevalence of dementia in hospitalized older adults and effects of comorbid dementia on patients' hospital course.

BACKGROUND AND AIMS: Many older adults with dementia are hospitalized for diagnoses other than dementia. We aimed to determine the prevalence of comorbid dementia among hospitalized older adults and evaluate its effects on their hospital course. METHODS: This retrospective case-control study reviewed the hospital records of all adults aged over 60 years admitted to one tertiary hospital in China from 2002 to 2012. In total, 34,888 patients meeting the age criterion were included. Patients admitted to departments of pediatrics, obstetrics and gynecology were not included. Demographic, clinical and outcome data from computerized discharge records were collected. Patients diagnosed with dementia at discharge by DSM-IV-TR criteria and MMSE scores formed the dementia group. All other patients were controls. Illness rating scale, comorbidities, mortality at discharge, dementia subtypes and long-term follow-up status for dementia patients were analyzed using comparative statistical methods (e.g., one-way ANOVA with Bonferroni pairwise comparison, Kruskal-Wallis and Mann-Whitney U test pairwise comparisons). RESULTS: A total of 918 patients (2.6% prevalence) had comorbid dementia, including Alzheimer's disease (39.1%) and vascular dementia (39.4%). Neurologic and respiratory system diseases were the most common main diagnoses for patients with comorbid dementia, who also had a higher percentage of level III or IV severity of main illness compared to controls and longer hospital stays (both P < 0.01). Mortality at discharge included 9.80% of the dementia group and 8.84% of controls (P = 0.312). CONCLUSION: Comorbid dementia has significant effects on hospital course of older adults with various main diagnoses, affecting length of stay, severity of illness, and mortality.

Prognosis of vascular mild cognitive impairment includes vascular dementia onset and death by cardiovascular disease: reanalysis from the Osaki-Tajiri project.

The relationship of predementia stage with cerebrovascular disease (CVD) has not been fully clarified. Following our Prevalence Study 1998 in Tajiri, Japan, Incidence Study 2003 disclosed that 17.9% of subjects developed vascular dementia (VaD). Some cases developed after stroke (type I), whereas others already met the criteria for subcortical VaD (SVD) despite very mild stage (Clinical Dementia Rating [CDR] 0.5) and progressed to mild stage (CDR 1) (type II). We hypothesized that prognosis of vascular mild cognitive impairment (MCI) included type II VaD or death due to causes associated with vascular risk factors. Prevalence Study 1998 included 497 randomly selected participants, including 346 with a CDR of 0, 119 with a CDR of 0.5, and 32 with a CDR of 1+. The first 2 groups were targeted for Incidence Study 2003. Based on the database, we reanalyzed the ratio of SVD in the subjects with CDR 0.5 and VaD, prognosis with or without CVD, and 2 types of VaD onset. The criteria for SVD were achieved by 67% of those with VaD and by 7% of those with vascular MCI (ie, CDR 0.5). In the CDR 0 group, CVD had no affect on prognosis; however, in the CDR 0.5 group, CVD had an affect on death by cardiovascular disease. The majority of subjects in the CDR 0 and CDR 0.5-CVD (-) groups were classified as type I, whereas all subjects in the CDR 0.5-CVD (+) group were type II. Although vascular MCI is treatable, it may progress to death as well as apparent dementia. Individuals with this "buried under the community" phenomenon of SVD should be targeted for secondary prevention interventions.

Survival in a large elderly population of patients with dementia and other forms of psychogeriatric diseases.

BACKGROUND: Dementia and other psychogeriatric diseases in elderly patients bring an increased risk of death. Better knowledge of prognosis in elderly patients affected by dementia or mental illness should be of great importance in order to improve care plans and assist in medical decisions. METHODS: We have investigated the survival time in 2,112 patients with dementia and other forms of psychogeriatric diseases, enrolled during 1990 to 2005 and followed up until 2009, and the influence of diagnoses, plasma homocysteine level, presence of vascular disease and renal impairment. RESULTS: The survival time after diagnosis in most diagnostic groups is about a third compared to an average population of similar age and sex. Age was the main predictor of survival time in all patients. CONCLUSIONS: All diagnoses, except in patients with subjective cognitive impairments, showed an increased mortality. These estimates can be used for prognosis and planning for patients, carers, service providers and policy makers.

Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size.

BACKGROUND AND PURPOSE: We sought to assess the efficacy and safety of donepezil in patients with vascular dementia (VaD) fulfilling National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria. METHODS: This international, multicenter, 24-week trial was conducted from March 2003 to August 2005. Patients (N=974; mean age, 73.0 years) with probable or possible VaD were randomized 2:1 to receive donepezil 5 mg/d or placebo. Coprimary outcome measures were scores on the Vascular-Alzheimer Disease Assessment Scale-Cognitive Subscale and Clinician's Interview-Based Impression of Change, plus carer interview. Analyses were performed for the intent-to-treat population with the last-observation-carried-forward method. RESULTS: Compared with placebo, donepezil-treated patients showed significant improvement from baseline to end point on the Vascular-Alzheimer Disease Assessment Scale-Cognitive Subscale (least-squares mean difference, -1.156; 95% CI, -1.98 to -0.33; P<0.01) but not on the Clinician's Interview-Based Impression of Change, plus carer interview. Patients with hippocampal atrophy who were treated with donepezil demonstrated stable cognition versus a decline in the placebo-treated group; in those without atrophy, cognition improved with donepezil versus relative stability with placebo. Results on secondary efficacy measures were inconsistent. The incidence of adverse events was similar across groups. Eleven deaths occurred in the donepezil group (1.7%), similar to rates previously reported for donepezil trials in VaD, whereas no deaths occurred in the placebo group. CONCLUSIONS: Patients treated with donepezil 5 mg/d demonstrated significant improvement in cognitive, but not global, function. Donepezil was relatively well tolerated; adverse events were consistent with current labeling. Mortality in the placebo group was unexpectedly low. The differential treatment response of VaD patients by hippocampal size suggests that hippocampal imaging warrants further investigation for understanding VaD.

Mortality and institutionalization in early survivors of stroke: the effects of cognition, vascular mild cognitive impairment, and vascular dementia.

We explored th effects of vascular mild cognitive impairment (VaMCI), vascular dementia (VaD), and other predictors on mortality and institutionalization in early survivors of ischemic stroke without previous dementia who had been admitted to a stroke unit. A total of 202 consecutive consenting eligible ischemic stroke survivors and a matched sample of 97 community controls were followed for up to 10 years. Data for 167 patients who underwent detailed assessment 3-6 months after stroke were analyzed to determine predictors of outcomes. Cumulative mortality rates for patients (and controls) were 27% (4%) for the first 5 years and rose to 83% (10%) by 10 years. Predictors of mortality were older age, any cognitive impairment, less independent function, and less education. Nursing home admission rates were 24% at 5 years and 32% at 10 years for patients and 0 for controls over 8.9 years. Predictors of institutionalization were less independent function and older age. Patients with ischemic stroke who survive the first week have moderate, lower-than-expected mortality rates in the first 5 years that increase thereafter. VaMCI, VaD, and functional decline are predictors of mortality, while functional decline and older age predict institutionalization.

[Do dementia patients living at home live longer than in a nursing home?]. / Leben Demenzkranke zu Hause länger als im Heim?

Many studies have shown that the number of new dementia diagnoses in Germany is increasing yearly. Thus, two social tasks are important: the adequate support and care of dementia patients, now and in the future, as well as covering the costs thereof. The survival period of dementia patients has a central meaning - especially for health policy planning. Therefore, the question of our 8-year follow-up study was whether living conditions affect the survival period of dementia patients? A total of 173 dementia outpatients (ICD-10 numbers F00 and F01) were screened for survival time and living conditions. For deceased patients, a close reference person was interviewed, and the exact date of death was recorded. For statistical evaluation, the Cox proportional hazard model was used and dying risks were determined. Our investigation shows that a clear difference exists in the survival period of dementia patients, according to whether they have lived at home or in a senior citizen's home. Patients in senior citizen's homes had a higher relative dying risk of around 53.1% (hazard ratio), than for those cared for at home (p=0.047). Prospective research is needed to gain more evidence about the impact of social factors, e.g., living conditions, on the survival time of demented patients.

MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population.

BACKGROUND AND PURPOSE: MRI biomarkers play an important role in the diagnostic work-up of dementia, but their prognostic value is less well-understood. We investigated if simple MRI rating scales predict mortality in a memory clinic population. METHODS: We included 1138 consecutive patients attending our memory clinic. Diagnostic categories were: subjective complaints (n=220), mild cognitive impairment (n=160), Alzheimer disease (n=357), vascular dementia (n=46), other dementia (n=136), and other diagnosis (n=219). Baseline MRIs were assessed using visual rating scales for medial temporal lobe atrophy (range, 0-4), global cortical atrophy (range, 0-3), and white matter hyperintensities (range, 0-3). Number of microbleeds and presence of infarcts were recorded. Cox-regression models were used to calculate the risk of mortality. RESULTS: Mean follow-up duration was 2.6 (+/-1.9) years. In unadjusted models, all MRI markers except infarcts predicted mortality. After adjustment for age, sex, and diagnosis, white matter hyperintensities, and microbleeds predicted mortality (white matter hyperintensities: hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; microbleeds: HR, 1.02 95% CI, 1.00-1.03; categorized: HR, 1.5; 95% CI, 1.1-2.0). The predictive effect of global cortical atrophy was restricted to younger subjects (HR, 1.7; 95% CI, 1.2-2.6). An interaction between microbleeds and global cortical atrophy indicated that mortality was especially high in patients with both microbleeds and global cortical atrophy. CONCLUSIONS: Simple MRI biomarkers, in addition to their diagnostic use, have a prognostic value with respect to mortality in a memory clinic population. Microbleeds were the strongest predictor of mortality.

Cause of death in patients with dementia disorders.

BACKGROUND: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. METHODS: The autopsy reports were studied on all patients (n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974-2004. RESULTS: The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. CONCLUSIONS: In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders.

Association of hyperglycemia episodes on long-term mortality in type 2 diabetes mellitus with vascular dementia: A population-based cohort study.

AIM: This study investigated the effect of severe hyperglycemia episodes on survival and associated factors related to risk of mortality in type 2 diabetes mellitus (DM) patients with dementia. METHODS: We enrolled all type 2 DM patients newly diagnosed as having dementia in Taiwan from 1998 to 2005. These patients were categorized into those who had hyperglycemia episodes and those who did not based on whether or not they had been hospitalized for hyperglycemia after dementia diagnosis. Factors independently associated with mortality were evaluated. RESULTS: Of 5314 patients identified, 303 (5.7%) had at least one hyperglycemia hospitalization. Patients with at least one hyperglycemia hospitalization had a 30% greater risk of mortality than those who had no such admissions (adjusted hazard ratio: 1.30, 95% confidence interval: 1.09-1.55). Other variables, including age, sex, geographical region, insurance amount, patient with congestive heart failure, cerebrovascular disease, renal disease, use of anti-hypertensive drugs, use of anti-lipid drugs, and use of insulin were independently associated with risk of mortality. CONCLUSION: Severe hyperglycemia is common in type 2 DM patients with dementia and it substantially shortens their life. The findings of this study suggest a great need to improve care in DM patients with dementia.

IL-1α and IL-6 predict vascular events or death in patients with cerebral small vessel disease-Data from the SHEF-CSVD study.

PURPOSE: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up. PATIENTS AND METHODS: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation. RESULTS: The mean age was 72 ± 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 ± 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1α (HR 1.4; 95%CI 1.09-1.8), IL-6 (1.4;1.1-2.2), hs-CRP (1.1;1.06-1.9), homocysteine (1.4;1.1-1.8), fibrinogen (1.4;1.05-2), and d-dimer (2.7;1.6-4.5) were significantly associated with the primary outcome. IL-1α (1.3;1.07-1.8), IL-6 (1.4;1.02-2.2), d-dimer (2.8;1.6-5) and homocysteine (1.4;1.1-1.8) remained significant after adjusting for age, sex and CSVD radiological markers. CONCLUSIONS: Our study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1α, IL-6 and recurrent stroke, other vascular events and death.

Early-onset dementia is associated with higher mortality.

BACKGROUND/AIMS: Our objective was to compare the mortality risks of patients with early- and late-onset dementia with non-demented controls of the same age range and to analyse the mortality risks in subtypes of dementia. METHODS: We included 1,203 subjects from our memory clinic. Patients with dementia were subdivided into 2 groups, with early- (<65 years) or late-onset dementia (>or=65 years), and compared with non-demented controls of the same age range. We used Cox proportional hazard models to estimate mortality risks. RESULTS: When compared to non-demented controls of the same age range, the patients with early-onset dementia had a strongly elevated mortality risk [hazard ratio (95% confidence interval) = 43.3 (3.1-600.4)], while those with late-onset dementia had a moderately increased mortality risk compared to older controls [hazard ratio (95% confidence interval) = 3.4 (1.8-6.2)]. An additional analysis showed that, adjusted for age, Alzheimer's disease seemed to have the most benign course, with a fourfold increased mortality risk. Dementia with Lewy bodies and vascular dementia (frequently seen at older age) and frontotemporal lobar degeneration and 'other dementias' (often found at younger age) had a six- to eightfold increased mortality risk. CONCLUSION: Dementia is a risk factor for death. Especially in young patients the impact of dementia on mortality is high.