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1.

Objective

To assess the influence of cognitive, functional and behavioral factors, co-morbidities as well as caregiver characteristics on driving cessation in dementia patients.

Methods

The study cohort consists of those 240 dementia cases of the ongoing prospective registry on dementia in Austria (PRODEM) who were former or current car-drivers (mean age 74.2 (±8.8) years, 39.6% females, 80.8% Alzheimer’s disease). Reasons for driving cessation were assessed with the patients’ caregivers. Standardized questionnaires were used to evaluate patient- and caregiver characteristics. Cognitive functioning was determined by Mini-Mental State Examination (MMSE), the CERAD neuropsychological test battery and Clinical Dementia Rating (CDR), activities of daily living (ADL) by the Disability Assessment for Dementia, behavior by the Neuropsychiatric Inventory (NPI) and caregiver burden by the Zarit burden scale.

Results

Among subjects who had ceased driving, 136 (93.8%) did so because of “Unacceptable risk” according to caregiver’s judgment. Car accidents and revocation of the driving license were responsible in 8 (5.5%) and 1(0.7%) participant, respectively. Female gender (OR 5.057; 95%CI 1.803–14.180; p = 0.002), constructional abilities (OR 0.611; 95%CI 0.445–0.839; p = 0.002) and impairment in Activities of Daily Living (OR 0.941; 95%CI 0.911–0.973; p<0.001) were the only significant and independent associates of driving cessation. In multivariate analysis none of the currently proposed screening tools for assessment of fitness to drive in elderly subjects including the MMSE and CDR were significantly associated with driving cessation.

Conclusion

The risk-estimate of caregivers, but not car accidents or revocation of the driving license determines if dementia patients cease driving. Female gender and increasing impairment in constructional abilities and ADL raise the probability for driving cessation. If any of these factors also relates to undesired traffic situations needs to be determined before recommendations for their inclusion into practice parameters for the assessment of driving abilities in the elderly can be derived from our data.  相似文献   

2.

Background

We aimed to calculate 3-year incidence of multimorbidity, defined as the development of two or more chronic diseases in a population of older people free from multimorbidity at baseline. Secondly, we aimed to identify predictors of incident multimorbidity amongst life-style related indicators, medical conditions and biomarkers.

Methods

Data were gathered from 418 participants in the first follow up of the Kungsholmen Project (Stockholm, Sweden, 1991–1993, 78+ years old) who were not affected by multimorbidity (149 had none disease and 269 one disease), including a social interview, a neuropsychological battery and a medical examination.

Results

After 3 years, 33.6% of participants who were without disease and 66.4% of those with one disease at baseline, developed multimorbidity: the incidence rate was 12.6 per 100 person-years (95% CI: 9.2–16.7) and 32.9 per 100 person-years (95% CI: 28.1–38.3), respectively. After adjustments, worse cognitive function (OR, 95% CI, for 1 point lower Mini-Mental State Examination: 1.22, 1.00–1.48) was associated with increased risk of multimorbidity among subjects with no disease at baseline. Higher age was the only predictor of multimorbidity in persons with one disease at baseline.

Conclusions

Multimorbidity has a high incidence at old age. Mental health-related symptoms are likely predictors of multimorbidity, suggesting a strong impact of mental disorders on the health of older people.  相似文献   

3.

Objectives

Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer''s disease (AD).

Methods

The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008–2011 were extracted and compared with age-related population data on a regional and national level.

Results

There were 20 305 patients registered in SveDem during 2008–2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80–84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD.

Conclusions

Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD.  相似文献   

4.

Objective

The present study aimed to determine prospective associations between work content after a working life of more than 20 years and serious mental illness among Japanese men aged 50 to 59 years, using a nationwide population-based survey.

Methods

Data were extracted from a national longitudinal survey of middle-aged and elderly persons previously conducted by the Ministry of Health, Labour and Welfare in Japan. We analyzed data across 10 work content categories for Japanese men who had been working in the same job type or industry for over 20 years. As part pf the survey, participants completed the Kessler (K)6 scale each year to determine their level of psychological distress (with scores ≥13 indicating serious mental illness). Cox discrete time proposal hazard regression analysis was used to examine potential associations between work content and serious mental illness from 2005 to 2010. Further adjustments were made for other sociodemographic characteristics and lifestyle factors.

Results

The current study involved a total of 11,942 participants with a mean (± standard deviation [SD]) of follow-up was 3.4 (± 2.0) years, during which time 892 participants (7.5%) had been classified as having a new-onset serious mental illness. Men who had worked in service jobs and in manufacturing jobs at baseline were more likely to develop serious mental illness than those in managerial jobs (hazard ratio 1.37, 1.30, 95% confidence intervals 1.04–1.80, 1.02–1.65) after adjustment for confounding variables.

Conclusion

These findings suggest that Japanese men aged 50 to 59 years who have worked in service and manufacturing jobs after a working life of over 20 years have an increased risk of serious mental illness during follow-up. Identifying the most at-risk work content category after a working life of over 20 years would be an essential part of providing more effective interventions for psychological distress among Japanese men in this age group.  相似文献   

5.

Background

Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia.

Methods and Findings

179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer''s disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson''s disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11–18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11–5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52–4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19–3.80), autonomic symptom score (HR per point 0–36: 1.055, 1.012–1.099), and Cornell depression score (HR per point 0–40: 1.053, 1.01–1.099). Higher levels of physical activity were protective (HR per point 0–9: 0.827, 0.716–0.956).

Conclusions

The management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority.  相似文献   

6.

Background

Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.

Methods

In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.

Findings

Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005).After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia.The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009.

Interpretation

A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.  相似文献   

7.

Introduction

Self-rated health (SRH) predicts chronic disease morbidity including cardiovascular disease (CVD). In a population-based cohort, we examined the association between SRH and incident CVD and whether this association was independent of socio-demographic, clinical and behavioural participant characteristics.

Methods

Population-based prospective cohort study (European Prospective Investigation of Cancer-Norfolk). 20,941 men and women aged 39–74 years without prevalent CVD attended a baseline health examination (1993–1998) and were followed for CVD events/death until March 2007 (mean 11 years). We used a Cox proportional hazards model to quantify the association between baseline SRH (reported on a four point scale – excellent, good, fair, poor) and risk of developing CVD at follow-up after adjusting for socio-demographic, clinical and behavioural risk factors.

Results

Baseline SRH was reported as excellent by 17.8% participants, good by 65.1%, fair by 16.0% and poor by 1.2%. During 225,508 person-years of follow-up, there were 55 (21.2%) CVD events in the poor SRH group and 259 (7.0%) in the excellent SRH group (HR 3.7, 95% CI 2.8–4.9). The HR remained significant after adjustment for behavioural risk factors (HR 2.6, 95% CI 1.9–3.5) and after adjustment for all socio-demographic, clinical and behavioural risk factors (HR 3.3, 95% CI 2.4–4.4). Associations were strong for both fatal and non-fatal events and remained strong over time.

Conclusions

SRH is a strong predictor of incident fatal and non-fatal CVD events in this healthy, middle-aged population. Some of the association is explained by lifestyle behaviours, but SRH remains a strong predictor after adjustment for socio-demographic, clinical and behavioural risk factors and after a decade of follow-up. This easily accessible patient-centred measure of health status may be a useful indicator of individual and population health for those working in primary care and public health.  相似文献   

8.
Although a clear risk of mortality is associated with obesity, the risk of mortality associated with overweight is equivocal. The objective of this study is to estimate the relationship between BMI and all‐cause mortality in a nationally representative sample of Canadian adults. A sample of 11,326 respondents aged ≥25 in the 1994/1995 National Population Health Survey (Canada) was studied using Cox proportional hazards models. A significant increased risk of mortality over the 12 years of follow‐up was observed for underweight (BMI <18.5; relative risk (RR) = 1.73, P < 0.001) and obesity class II+ (BMI >35; RR = 1.36, P <0.05). Overweight (BMI 25 to <30) was associated with a significantly decreased risk of death (RR = 0.83, P < 0.05). The RR was close to one for obesity class I (BMI 30–35; RR = 0.95, P >0.05). Our results are similar to those from other recent studies, confirming that underweight and obesity class II+ are clear risk factors for mortality, and showing that when compared to the acceptable BMI category, overweight appears to be protective against mortality. Obesity class I was not associated with an increased risk of mortality.  相似文献   

9.

Background

Association of frailty with adverse clinical outcomes has been reported in Western countries, but data from the Asian population are scarce. This study aimed to evaluate the epidemiology of frailty among community-dwelling middle-aged and elderly population and to explore its association with musculoskeletal health in Taiwan.

Methods

I-Lan Longitudinal Aging Study (ILAS) data were retrieved for this study. Frailty was defined by the Fried’s criteria; a comparison of demographic characteristics, physical performance, and body composition, including skeletal muscle mass and bone mineral density (BMD), as well as recent falls, history of hip fractures and the functional status of subjects with different frailty statuses were accomplished.

Results

Overall, the data of 1,839 participants (mean age: 63.9±9.3 years, male 47.5%) were obtained for analysis. The prevalence of pre-frailty was 42.3% in men and 38.8% in women, whereas the prevalence of frailty was 6.9% and 6.7% in men and women, respectively. Frailty was significantly associated with older age, the male gender, larger waist circumference, lower skeletal muscle index, lower hip BMD, poorer physical function, poorer nutritional status, and poorer cognitive function. Also, frailty was significantly associated with osteoporosis (OR: 7.73, 95% CI: 5.01–11.90, p<0.001), history of hip fractures (OR: 8.66, 95% CI: 2.47–30.40, p = 0.001), and recent falls (O.R: 2.53, 95% CI: 1.35–4.76, p = 0.004).

Conclusions

Frailty and pre-frailty, in Taiwan, was closely associated with recent falls, history of hip fractures and osteoporosis among community-dwelling people 50 years of age and older. Furthermore, frailty intervention programs should take an integrated approach towards strengthening both and muscle mass, as well as prevention of falls.  相似文献   

10.
11.
目的在实验豚鼠饲养盒内增加梯形和管形两种不同的模具,进行环境丰富化模具对豚鼠生长及行为影响的研究。方法每组豚鼠饲养4周,每周称1次体重,记录体重变化趋势,并观察豚鼠行为变化。结果放入模具的豚鼠生长情况优越于对照组,管形模具优于其他实验组。结论增加环境丰富化模具有利于豚鼠生长,且管形模具更接近豚鼠自然洞穴状态,更加有利于豚鼠实现自然躲藏行为和良好的生长、生活。  相似文献   

12.
13.
The Ca(2+) binding sites of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum (SR) have been identified as two high-affinity sites orientated towards the cytoplasm, two sites of low affinity facing the lumen, and a transient occluded species that is isolated from both membrane surfaces. Binding and release studies, using (45)Ca(2+), have invoked models with sequential binding and release from high- and low-affinity sites in a channel-like structure. We have characterised turnover conditions in isolated SR vesicles with oxalate in a Ca(2+)-limited state, [Ca(2)](lim), where both high- and low-affinity sites are vacant in the absence of chelators (Biochim. Biophys. Acta 1418 (1999) 48-60). Thapsigargin (TG), a high-affinity specific inhibitor of the Ca(2+)-ATPase, released a fraction of total Ca(2+) at [Ca(2+)](lim) that accumulated during active transport. Maximal Ca(2+) release was at 2:1 TG/ATPase. Ionophore, A23187, and Triton X-100 released the rest of Ca(2+) resistant to TG. The amount of Ca(2+) released depended on the incubation time at [Ca(2+)](lim), being 3.0 nmol/mg at 20 s and 0.42 nmol/mg at 1000 s. Rate constants for release declined from 0. 13 to 0.03 s(-1). The rapidly released early fraction declined with time and k=0.13 min(-1). Release was not due to reversal of the pump cycle since ADP had no effect; neither was release impaired with substrates acetyl phosphate or GTP. A phase of reuptake of Ca(2+) followed release, being greater with shorter delay (up to 200 s) following active transport. Reuptake was minimal with GTP, with delays more than 300 s, and was abolished by vanadate and at higher [TG], >5 microM. Ruthenium red had no effect on efflux, indicating that ryanodine-sensitive efflux channels in terminal cisternal membranes are not involved in the Ca(2+) release mechanism. It is concluded that the Ca(2+) released by TG is from the occluded Ca(2+) fraction. The Ca(2+) occlusion sites appear to be independent of both high-affinity cytoplasmic and low-affinity lumenal sites, supporting a multisite 'in line' sequential binding mechanism for Ca(2+) transport.  相似文献   

14.
The Ruff Figural Fluency Test (RFFT) is a cognitive test to measure executive function. Longitudinal studies have shown that repeated testing improves performance on the RFFT. Such a practice effect may hinder the interpretation of test results in a clinical setting. Therefore, we investigated the longitudinal performance on the RFFT in persons aged 35–82 years. Performance on the RFFT was measured three times over an average follow-up period of six years in 2,515 participants of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study in Groningen, the Netherlands: 53% men; mean age (SD), 53 (10) years. The effect of consecutive measurements on performance on the RFFT was investigated with linear multilevel regression models that also included age, gender, educational level and the interaction term consecutive measurement number x age as independent variables. It was found that the mean (SD) number of unique designs on the RFFT increased from 73 (26) at the first measurement to 79 (27) at the second measurement and to 83 (26) at the third measurement (p<0.001). However, the increase per consecutive measurement number was negatively associated with age and decreased with 0.23 per one-year increment of age (p<0.001). The increase per consecutive measurement number was not dependent on educational level. Similar results were found for the median (IQR) number of perseverative errors which showed a small but statistically significant increase with repeating testing: 7 (3–13) at the first measurement, 7 (4–14) at the second measurement and 8 (4–15) at the third measurement (p trend = 0.002). In conclusion, the performance on the RFFT improved by repeating the test over an average follow-up period of three to six years. This practice effect was the largest in young adults and not dependent on educational level.  相似文献   

15.
BackgroundResearch has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI.ConclusionsA variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.  相似文献   

16.

Objective

We evaluated the postmortem changes of striated muscle by comparing computed tomography (CT) images obtained postmortem and antemortem in the same patients.

Materials and Methods

We studied 33 consecutive patients who underwent antemortem CT, postmortem CT, and pathological autopsy in our tertiary care hospital between April 2009 and December 2010. Postmortem CT was performed within 20 h after death and was followed by pathological autopsy. Pathological autopsy confirmed the absence of muscular diseases such as amyotrophic lateral sclerosis, muscular dystrophy, myositis, and myasthenia, in all of the patients. The CT attenuation values of four cardiac muscle sites (anterior wall of the left ventricle, left ventricular free wall, posterior wall of the left ventricle, and the ventricular septum) and two skeletal muscle sites (the pectoralis major muscle and the erector spinae muscle) were compared between antemortem and postmortem CT using paired t test.

Results

Striated muscle had significantly greater attenuation on postmortem CT than on antemortem CT (P<0.001) in all six tissue sites. No significant association was found between postmortem change in the CT attenuation of striated muscle and gender, age, or elapsed time since death.

Conclusion

This is the first longitudinal study to show hyperattenuation of striated muscle on postmortem CT images compared with antemortem CT images in the same patients.  相似文献   

17.
Ca(2+)-dependent transmitter release is the most important signaling mechanism for fast information transfer between neurons. Transmitter release takes places at highly specialized active zones with sub-micrometer dimension, which contain the molecular machinery for vesicle docking and -fusion, as well as a high density of voltage-gated Ca(2+) channels. In the absence of direct evidence for the ultrastructural localization of Ca(2+) channels at CNS synapses, important insights into Ca(2+) channel-vesicle coupling has come from functional experiments relating presynaptic Ca(2+) current and transmitter release, at large and accessible synapses like the calyx of Held. First, high slope values in log-log plots of transmitter release versus presynaptic Ca(2+) current indicate that multiple Ca(2+) channels are involved in release control of a single vesicle. Second, release kinetics in response to step-like depolarizations revealed fast- and slowly releasable sub-pools of vesicles, FRP and SRP, which, according to the "positional" model, are distinguished by a differential proximity to Ca(2+) channels. Considering recent evidence for a rapid conversion of SRP- to FRP vesicles, however, we highlight that multivesicular release events and clearance of vesicle membrane from the active zone must be taken into account when interpreting kinetic release data. We conclude that the careful kinetic analysis of transmitter release at presynaptically accessible and molecularly targeted synapses has the potential to yield important insights into the molecular physiology of transmitter release.  相似文献   

18.

Background

Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS).

Methods and Findings

A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%).

Conclusions

Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively “pure,” but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia. Please see later in the article for the Editors'' Summary  相似文献   

19.
In acute leukaemias there was a stable plateau in the survival curve at 45% after two years if grafted in first complete remission (n = 20) but only 13% of the patients are disease-free alive if grafted in a more advanced stage of the disease (n = 8). In 16 patients transplanted for chronic myeloid leukaemia the overall survival is 40%, in cases with graft-versus-host disease (GVHD) prevention by cyclosporine survival rate could be improved. Only 8 patients with severe aplastic anaemia, partially in low performance status were able to be transplanted; three died of infections, another by acute GVHD. The fatal complications in our study characterize the international well-known major problems in BMT: GVHD, interstitial pneumonitis, infections, graft failure in aplastic anaemia and recurrence of leukaemia, especially in more advanced leukaemia stage.  相似文献   

20.

Background

Predictors of unscheduled return visits (URV), best time-frame to evaluate URV rate and clinical relationship between both visits have not yet been determined for the elderly following an ED visit.

Methods

We conducted a prospective-observational study including 11,521 patients aged ≥75-years and discharged from ED (5,368 patients (53.5%)) or hospitalized after ED visit (6,153 patients). Logistic Regression and time-to-failure analyses including Cox proportional model were performed.

Results

Mean time to URV was 17 days; 72-hour, 30-day and 90-day URV rates were 1.8%, 6.1% and 10% respectively. Multivariate analysis indicates that care-pathway and final disposition decisions were significantly associated with a 30-day URV. Thus, we evaluated predictors of 30-day URV rates among non-admitted and hospitalized patient groups. By using the Cox model we found that, for non-admitted patients, triage acuity and diagnostic category and, for hospitalized patients, that visit time (day, night) and diagnostic categories were significant predictors (p<0.001). For URV, we found that 25% were due to closely related-clinical conditions. Time lapses between both visits constituted the strongest predictor of closely related-clinical conditions.

Conclusion

Our study shows that a decision of non-admission in emergency departments is linked with an accrued risk of URV, and that some diagnostic categories are also related for non-admitted and hospitalized subjects alike. Our study also demonstrates that the best time frame to evaluate the URV rate after an ED visit is 30 days, because this is the time period during which most URVs and cases with close clinical relationships between two visits are concentrated. Our results suggest that URV can be used as an indicator or quality.  相似文献   

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