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Subjective cognitive decline (SCD) and depressive symptoms (DS) frequently co-occur prior to dementia. However, the temporal sequence of their emergence and their combined prognostic value for cognitive decline and dementia is unclear.Temporal relationships of SCD, DS and memory decline were examined by latent difference score modeling in a high-aged, population-based cohort (N = 3217) and validated using Cox-regression of dementia-conversion. In 334 cognitively unimpaired SCD-patients from memory-clinics, we examined the association of DS with cognitive decline and with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers.In the population-based cohort, SCD preceded DS. High DS were associated with increased risk of dementia conversion in individuals with SCD. In SCD-patients from memory-clinics, high DS were associated with greater cognitive decline. CSF Aß42 predicted increasing DS.SCD typically precedes DS in the evolution to dementia. SCD-patients from memory-clinics with DS may constitute a high-risk group for cognitive decline.Subjective cognitive decline (SCD) precedes depressive symptoms (DS) as memory declines. Emerging or persistent DS after SCD reports predict dementia. In SCD patients, more amyloid pathology relates to increasing DS. SCD patients with DS are at high risk for symptomatic progression.

OBJECTIVES There is a lack of studies identifying the correlates of institutionalization specifically among the oldest old. Therefore, our aim was to fill this gap in knowledge. METHODS Cross-sectional data (Follow up wave 9; n = 633 observations in the analytical sample) were used from the multicenter prospective cohort study "Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" Correlates of institutionalization among the oldest old-Evidence from a multicenter cohort study. The sample consists of primary care patients aged 86 years and over (mean 90.5 years, SD: 2.9 years). Sociodemographic and health-related independent variables were included in our regression model. Institutionalization was defined as living in a nursing home or an old-age home (not including assisted living facilities). RESULTS Out of the 633 participants, 502 individuals (79.3%) did not live in an institutionalized setting, whereas 73 individuals (20.7%) lived in an institutionalized setting. Multiple logistic regressions showed that the likelihood of institutionalization increased with being divorced/widowed/single (compared to being married; OR: 5.35 [95% CI: 1.75-16.36]), the presence of social isolation (OR: 2.07 [1.20-3.59]), more depressive symptoms (OR: 1.11 [1.01-1.23]), increased cognitive impairment (OR: 1.67 [1.31-2.15]) and higher levels of frailty (OR: 1.48 [1.07-2.06]). CONCLUSION The study findings identified various sociodemographic and health-related factors associated with institutionalization among the oldest old. Longitudinal studies are required to gain further insights into these associations.

Objectives Previous studies have observed protective effects of high mental demands at work on cognitive functioning and dementia risk. However, it is unclear what types of demands drive this effect and whether this effect is subject to a person's genetic risk. We investigated to what extent eight different types of mental demands at work together with the APOE e4 allele, a major risk gene for late-onset Alzheimer's disease, affect cognitive functioning in late life. Methods/design The population-based German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe, n=2,154) followed cognitively healthy individuals aged 75 years and older in seven assessment waves. Cognitive functioning was assessed via the mini-mental status examination. Results Mixed-effects modeling (adjusted for education, gender, marital status, stroke, depression, and diabetes) indicated that participants who had an occupational history of working in jobs with high compared to low demands in 'Language & Knowledge', 'Pattern detection', 'Information processing', and 'Service' had a slower cognitive decline. APOE e4-allele carriers had an accelerated cognitive decline, but this decline was significantly smaller if they had a medium compared to a low level of demands in contrast to non-carriers. Conclusions Our longitudinal observations suggest that cognitive decline could be slowed by an intellectually enriched lifestyle even in risk gene carriers. Fostering intellectual engagement throughout the life-course could be a key prevention initiative to promote better cognitive health in old age. This article is protected by copyright. All rights reserved.

Introduction Subjective cognitive decline (SCD) is a risk condition for dementia, including dementia of Alzheimer type (DAT). Methods We report sensitivity, specificity, positive and negative predictive values (PPV, NPV) for conversion to all-cause dementia, and DAT in different SCD types (decline in memory, assocated worries, longitudinal consitency, of the AgeCoDe study (n = 2.402, 12 years follow-up). Results 82.7% of those converting to any dementia and 84.4% of those converting with DAT at follow-up, reported memory decline and fulfilled criteria of SCD at least at one time point before. SCD with worries at two consecutive time points showed a specificity of 92.2% for any dementia and also for DAT as well as a PPV of 44.3% for any dementia and of 36.9% for DAT at follow-up at the expense of low sensitivity. Discussion Different SCD subtypes were either sensitive or specific for future all-cause dementia and DAT in cognitively unimpaired individuals. Modest PPV of the most specific SCD subtypes were achieved in this low prevalence population.

OBJECTIVE Subjective cognitive decline (SCD), the earliest symptom in preclinical Alzheimer's disease (AD), is insufficient to identify individuals at risk for AD dementia. Therefore, we aimed to investigate whether function in instrumental activities of daily living (IADL) contributes to identification. METHODS We analysed data of cognitively unimpaired participants of the prospective German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) and its extension, the Study on Needs, Health Service Use, Costs and Health-related Quality of Life in a Large Sample of Oldest-old Primary Care Patients (AgeQualiDe), collected over 10.5 years. Development of AD dementia was quantified as incidence rates (IRs) per 1000 person-years. Cox regression was used to assess the association of SCD and IADL function in regard to incident AD dementia. RESULTS Of 1467 included individuals, 792 (54.0%) reported SCD at baseline. Impaired IADL were present in 50 (3.4%) individuals. IR for AD dementia was highest in individuals with SCD and impaired IADL (49.7; 95% CI, 24.8-99.3). Unadjusted and adjusted Cox analyses revealed an increased AD dementia risk for individuals with SCD and impaired IADL (uHR = 6.1; 95% CI, 2.9-13.0; P

OBJECTIVE To analyze the association of anxiety symptoms with health care use and costs in people aged 85 and older. METHODS Baseline data from AgeQualiDe (N = 856), a multicenter prospective cohort study of primary care patients aged 85 and older, were analyzed. Anxiety symptoms (Geriatric Anxiety Inventory-Short Form) and health care use were assessed via questionnaires. Health care use was monetarily valued using German unit costs to obtain sectoral (inpatient, outpatient, nursing care, medical supplies, and medication) and total costs. Health care use and costs were analyzed in regression models as a function of anxiety symptoms, as well as relevant covariates (predisposing, enabling, and other need characteristics based on the Behavioral Model of Health Care Use). RESULTS On a descriptive level, people with increased anxiety symptoms (12% of the sample) incurred on average € 10 909 (SD: 16 023) in the last 6 months, 31% more than those without increased anxiety (€ 8303, SD: 11 175; P = 0.12). Adjusting for predisposing, enabling, and other need characteristics, anxiety symptoms were not significantly associated with health care use or costs. Specifically, need characteristics (morbidity, cognitive decline, and functional impairment) were associated with total or sectoral costs, depending on the cost category analyzed. CONCLUSION In a sample of people of the oldest-old age group, the severity of anxiety symptoms was not associated with health care use or costs, when adjusting for relevant covariates. A longitudinal analysis could assess whether a change in anxiety symptom severity is associated with health care use or costs in old age.

Introduction Previous studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental work demands and whether it is exposure dependent. Methods Patients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315). Results We observed a significantly lower dementia risk in individuals with a higher level of "information processing" (HR, 0.888), "pattern detection" (HR, 0.878), "mathematics" (HR, 0.878), and "creativity" (HR, 0.878). Yet, exposure-dependent effects were only significant for "information processing" and "pattern detection." Discussion Our longitudinal observations suggest that dementia risk may be reduced by some but not all types of mental work demands.

Purpose: Since the beginning of the 21st century, serious adverse events and an increased risk of mortality have been documented in patients with dementia treated with antipsychotics. The aim of this study was to assess antipsychotic prescribing in patients with incident dementia compared with a non-demented control group. Methods: We analysed the claims data of a German health insurance company for incident dementia patients and age-matched and sex-matched non-demented controls aged 65 years and older in 2004 to 2006. The data were used to analyse the prescribing patterns of antipsychotics in the year of dementia incidence. We estimated odds ratios stratified by age, sex, care setting and care dependence and in a multivariate logistic regression. Results: The 1848 patients with and 7385 persons without dementia were on average 78.8 years old (standard deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients received antipsychotics compared with 4.3% of the controls (ORcrude: 7.61; 95%CI: 6.52–8.87). An increase in care level, age, female gender and living in a nursing home is associated with a considerably higher prevalence of at least one prescription for antipsychotics. After adjusting for all these variables, a significant influence of age could no longer be found. Conclusions: The results show that antipsychotics play an important role in dementia care—despite the risk of adverse events. Further research is needed with regard to safe pharmacological and non-pharmacological approaches for the behavioural and psychological symptoms of dementia in this vulnerable group.

Objectives: To compare the accuracy of commonly used tasks with that of the Visual Association Test (VAT), a conceptually different test involving cued recall of pictorial stimuli, in the recognition of dementia within primary care. Design: A cross-sectional diagnostic study of concurrent validity. Setting: Twenty-nine German primary care practices. Participants: Four hundred twenty-three individuals in primary care participating in a longitudinal cohort study. Measurements: Participants underwent a comprehensive neuropsychological interview. The validated clinical dementia diagnosis was used as reference standard. Index tests comprised the VAT, Mini-Cog, clock drawing, verbal fluency, episodic memory, and subjective complaints. Validity parameters were calculated; possible confounders of test performance (age, sex, education, comorbidity, depression, language) were evaluated. Results: Twenty-one participants (5%) had dementia according to the reference standard. The VAT distinguished dementia from nondementia with a sensitivity of 95.2% (95% confidence interval (CI) = 86.1�100.0), a specificity of 96.0% (95% CI = 94.1�97.9), a positive predictive value (PPV) of 55.6% (95% CI = 39.3�71.8), and a negative predictive value (NPV) of 99.7% (95% CI = 99.2�100.0). The next-most-accurate tasks were the Mini-Cog and immediate and delayed recall. Their sensitivity and NPV are similar to those of the VAT, but their PPV and specificity were significantly lower than those of the VAT. Age and depression affected all test scores. Conclusion: The VAT (cued recall of pictorial material) is superior to other tasks for the recognition of dementia in terms of higher specificity and PPV. Age-specific cutoff scores may improve the validity of all tests.

Androgen receptor (AR) expression profile in the different Gleason patterns (GP) of primary prostate cancers and nodal metastases is unknown. More information about AR distribution is needed to optimize evaluation methods and to better understand the role of AR in development and progression of prostate cancer.

SUMMARY Background Little is known about the prevalence and risk factors of alcohol problems among older people (especially those aged 75 years and more). The aims of this study were to report alcohol consumption patterns and to determine their association with socio-demographic variables and health characteristics. Method 3224 non-demented subjects aged 75 and over and attending general practitioners (GPs) (n ¼ 138) in an urban area of Germany were studied by structured clinical interviews including detailed assessment of alcohol consumption patterns distinguishing between abstainers, moderate drinkers and at-risk drinkers (>20 g of alcohol for women and >30 g of alcohol for men). Results A high proportion (50.1%) of the sample were abstainers, 43.4% were moderate drinkers. The prevalence of at-risk alcohol consumption was 6.5% (95% CI 5.6–7.4). Rates were significantly higher for men (12.1%; 95% CI 10.2–14.0) compared to women (3.6%; 95% CI 2.8–4.4). After full adjustment for confounding variables we found that compared to moderate drinking abstaining from alcohol was significantly associated with female gender, lower education, and mobility impairment. Compared to moderate drinking at-risk drinking was significantly higher among men, individuals with a liver disease, and current smokers. Conclusions Multivariate analysis revealed that, apart from liver disease, at-risk drinking in a non-demented population aged 75 and over was associated with relatively good physical and mental health. Nevertheless, public prevention measures should focus on at-risk drinkers to make them aware of potential risks of high alcohol consumption in old age. Copyright # 2009 John Wiley & Sons, Ltd.

Objectives: Friend leukemia integration- 1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph - CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. Methods: Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph - CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. Results: Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph - CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph - CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph - CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. Conclusion: Fli-1 is rather constitutively expressed by bone marrow cells in Ph - CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph - CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded.

Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.

Thirty-four alcoholics were treated with acupuncture to the ear and the body in a randomized single-blind placebo-controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add-on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol-related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon-W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.

Proliferative activity of tumour cells, as assessed by the Ki-67 labelling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. Meaningful application of the immunohistochemically determined tumour cell growth fraction in clinical decision-making requires information about its inter-laboratory reproducibility. To assess the reproducibility of Ki-67 determined growth fraction, a multi-centre immunohistochemical trial was performed with 172 participating laboratories, each testing 30 different tissue samples. Evaluating 5160 Ki-67 labelling indices with a newly developed tissue microarray, good inter-observer reproducibility but high inter-laboratory variability was found. Reassessment of all stainings revealed considerable inter-laboratory differences in the intensity and frequency of labelled nuclei, suggesting that antigen retrieval or staining techniques are predominantly responsible for the inter-laboratory variability found in this trial. Consequently, cut-off levels for Ki-67, suggested to distinguish prognostic subgroups in tumours, appear to have limited reproducibility in a multi-centre approach. It is concluded that there is a need to standardize the immunohistochemical determination of the Ki-67 labelling index when it is used as a prognostic indicator in surgical pathology.

In this paper, a statistical model for clinical trials is presented for the special situation that a varying and unstructered number of binary responses is obtained from each subject. The assumptions of the model are the following: 1.) For each subject there is a (constant) individual Bernoulli parameter determining the distribution of the binary responses of this subject. 2.) The Bernoulli parameters associated with the subjects are realizations of independent random variables with distributions Pg in treatment group g(g = 1, 2, …, G). 3.) Given the value of the Bernoulli parameter, the observations are stochastically independent within each subject. Under these assumptions, a test statistic is derived to test the hypothesis H0:E(P1) = E(P2) = … = E(PG). It is proven and demonstrated by simulations, that the test statistic asymptotically (i.e. for a large number of subjects) follows the X2-distribution.