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Introduction: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive change after stroke are unclear. We aimed to measure changes in the trajectory of cognitive function following a first stroke, controlling for pre-stroke cognitive performance using diverse population-based studies from the Cohort Studies of Memory in an International Consortium (COSMIC). Methods: Fourteen longitudinal cohorts from 11 countries from Asia, Africa, North America, South America, Europe, and Australia contributed data. Cognitive domain scores were formed by selecting the most common test administered amongst studies in each domain (memory, processing speed, language, and executive function) and the scores standardised; global cognition was the standardised average of the 4 domains and the primary outcome. One-stage IPD meta- analysis with linear mixed model and regression discontinuity design was used to model the change in cognitive function. Time-dependent incident stroke, age, time in study, and time since stroke were included in the basic model. In the full model we adjusted for sex, education, ethno- racial group, study period and potential confounders significant in the basic model at p

Abstract Background Although the detrimental health effects of alcohol are well established, consumption levels are high in many high-income countries such as Germany. Improving alcohol health literacy presents an integrated approach to alcohol prevention and an important complement to alcohol policy. Our aim was to identify and prioritize measures to enhance alcohol health literacy and hence to reduce alcohol consumption, using Germany as an example. Methods A series of recommendations for improving alcohol health literacy were derived from a review of the literature and subsequently rated by five experts. Recommendations were rated according to their likely impact on enhancing (a) alcohol health literacy and (b) reducing alcohol consumption. Inter-rater agreement was assessed using a two-way intra-class correlation coefficient (ICC). Results Eleven recommendations were established for three areas of action: (1) education and information, (2) health care system, and (3) alcohol control policy. Education and information measures were rated high to increase alcohol health literacy but low to their impact on alcohol consumption, while this pattern was reversed for alcohol control policies. The ratings showed good agreement (ICC: 0.85–0.88). Conclusions Improving alcohol health literacy and reducing alcohol consumption should be considered complementary and become part of a comprehensive alcohol strategy to curb the health, social, and economic burden of alcohol.

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies.Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe.Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards.Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression.

In the course of the recognition of mental health as an essential component of population health, the Robert Koch Institute has begun developing a Mental Health Surveillance (MHS) system for Germany. MHS aims to continuously report data for relevant mental health indicators, thus creating a basis for evidence-based planning and evaluation of public health measures. In order to develop a set of indicators for the adult population, potential indicators were identified through a systematic literature review and selected in a consensus process by international and national experts and stakeholders. The final set comprises 60 indicators which, together, represent a multidimensional public health framework for mental health across four fields of action. For the fifth field of action ‘Mental health promotion and prevention’ indicators still need to be developed. The methodology piloted proved to be practicable. Strengths and limitations will be discussed regarding the search and definition of indicators, the scope of the indicator set as well as the participatory decision-making process. Next steps in setting up the MHS will be the operationalisation of the single indicators and their extension to also cover children and adolescents. Given assured data availability, the MHS will contribute to broadening our knowledge on population mental health, supporting a targeted promotion of mental health and reducing the disease burden in persons with mental disorders.

BackgroundMild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI – “mild neurocognitive disorder” (mild NCD) – this diagnosis is still based on clinical criteria.MethodsTo link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63–79 years old) were selected from the Leipzig-population-based study of adults (LIFE).ResultsSerum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.ConclusionOur findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Abstract Background Sleep disorders and vitamin D deficiency are highly prevalent health problems. Few studies examined the effect of vitamin D concentrations on objectively measured sleep with high methodological quality and temporal proximity. Previous analysis within the LIFE-Adult-Study suggested that a lower concentration of serum vitamin D was associated with both shorter and later night sleep. However, no conclusion about underlying mechanisms could be drawn. We addressed the question whether this relationship is explained by the presence of depressive syndromes, which are linked to both vitamin D deficiency and sleep disturbances. Methods It was investigated whether the association of vitamin D concentrations and night sleep parameters is mediated or moderated by depressive symptomatology. We investigated a subset (n = 1252) of the community sample from the LIFE-Adult-Study, in which sleep parameters had been objectively assessed using actigraphy, based on which two sleep parameters were calculated: night sleep duration and midsleep time. Serum 25(OH) D concentrations were measured using an electrochemiluminescence immunoassay. Depressive symptomatology was evaluated with the Centre for Epidemiological Studies Depression Scale. The mediation effect was analyzed by using Hayes’ PROCESS macro tool for SPSS for Windows. Results The depressive symptomatology was neither significantly associated with night sleep duration nor midsleep time. The associations between vitamin D concentrations and night sleep duration/midsleep time through mediation by depressive symptomatology were not significant. Corresponding moderator analyses were also non-significant. Conclusion The associations between vitamin D concentrations and night sleep parameters (sleep duration and midsleep time) seem to be neither mediated nor moderated by depressive symptomatology.

BackgroundGhrelin and the adipokines leptin and adiponectin have been suggested to be involved in mood and anxiety regulation and to be altered in affective disorders. However, studies investigating the association between ghrelin, leptin and adiponectin and depressive symptomatology are scarce but might contribute to a better understanding of their involvement in mood regulation. We thus aimed investigating the association between depressive symptomatology and total ghrelin as well as leptin and adiponectin serum levels in a large population-based sample.MethodsTotal serum ghrelin, adiponectin and leptin levels were determined in 1666 subjects of a population-based cross-sectional study (“LIFE”). The Center for Epidemiological Studies Depression Scale (CES-D) and the Inventory of Depressive Symptoms – Self Rating (IDS-SR) were administered. Multiple linear regression analyses were conducted to examine the association between total serum ghrelin, leptin and adiponectin and the intensity of depressive symptoms.ResultsIn the total sample (n = 1,092), neither ghrelin nor leptin or adiponectin serum levels showed a significant association with CES-D or IDS-SR sum scores (N = 1,092) or in depressed/non-depressed subjects. Leptin serum levels showed a significantly positive association with IDS-SR sum scores in elderly men (≥60 years; β = 0.122, 95% CI: 0.009; 0.236; p = 0.035).ConclusionOur study suggests that peripheral levels of ghrelin and adipokines in a cross-sectional study design might not be sufficient to measure their involvement in depression, suggesting that associations are more complex and multi-layered.

Abstract Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.

Abstract Background In Germany, patients are consulting general practitioners increasingly frequently, resulting in a high burden on the healthcare system. This study aimed to identify factors associated with frequent primary care attendance in the German healthcare system. Methods The German Health Interview and Examination Survey for Adults (DEGS) is part of Germany’s national health monitoring, and includes a large representative sample of the German population aged 18–79 years. We defined the 10% of participants with the highest number of general practitioner contacts in the preceding 12 months as frequent attenders of primary care services. Binary logistic regression models with average marginal effects were used to identify potential determinants for frequent use of primary care services. Results The sample comprised 7956 participants. Significant effects on frequent use of primary care were observed for low socioeconomic status, stressful life events, factors related to medical need for care such as medically diagnosed chronic conditions and for subjective health. In the full model, the number of non-communicable diseases and subjective health status had the strongest effect on frequent primary care use. We found an interaction effect suggesting that the association between subjective health status and frequent attendance vanishes with a higher number of non-communicable diseases. Conclusions We observed strong associations between frequent primary care attendance and medical need for care as well as subjective health-related factors. These findings suggest that better coordination of care may be a preferred method to manage health services utilization and to avoid redundant examinations and uncoordinated clinical pathways. Further research is needed to clarify moderating and mediating factors contributing to high utilization of primary care services.

Abstract Background Late-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective. Psychotherapy may be particularly beneficial for LLD due to specific psychological conditions in old age and a low risk of side effects. Although cognitive behavioural therapy (CBT) is highly established and effective in depression in young and mid-life there is only a limited number of small studies on CBT in LLD. An LLD-specific CBT has not yet been compared to an active, but unspecific supportive psychological intervention in a multicentre trial. Methods Here we present the design of the CBTlate trial, which is a multicentre, randomized, observer-blinded, active-controlled, parallel group trial. CBTlate aims at including 248 patients with LLD of both genders at 7 sites in Germany. The purpose of the study is to test the hypothesis that a 15-session individually-delivered CBT specific for LLD is of superior efficacy in reducing symptoms of depression in comparison with a supportive unspecific intervention (SUI) of the same quantity. The intervention includes 8 weeks of individual treatment sessions twice per week and a follow-up period of 6 months after randomization. The primary end point is the severity of depression at the end of treatment measured by the self-rated 30-item Geriatric Depression Scale (GDS). Secondary endpoints include depressive symptoms at week 5 and at follow-up (6 months after randomization). Additional secondary endpoints include the change of depressive symptoms assessed with a clinician-rating-scale and a patient reported outcome instrument for major depressive disorder, anxiety symptoms, sleep, cognition, quality of life, and overall health status from baseline to end-of treatment and to end of follow-up. Add-on protocols include MRI and the collection of blood samples. Discussion This study is the first multicentre trial of a specific CBT intervention for LLD compared to an unspecific supportive psychological intervention administered in a specialist setting. It has important implications for developing and implementing efficient psychotherapeutic strategies for LLD and may be a significant step to broaden treatment options for people suffering from LLD. Trial registration ClinicalTrials.gov (NCT03735576, registered on 24 October 2018); DRKS (DRKS00013769, registered on 28 June 2018).

Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.

Selecting relevant indicators is an important step in the development of public health monitoring for older people. Indicators can be used to combine information comprehensively from various data sources and enable recurring, comparable findings to be made about the health of older people. Indicators were systematically compiled from existing international monitoring systems. An indicator set on health in old age was developed using a multistage, structured consensus-based process together with an interdisciplinary panel of experts. The resulting 18 indicators were assigned to three health areas: (1) environmental factors, (2) activities and participation, and (3) personal factors. Data sources that can be used for the indicators are the health surveys within the framework of the Robert Koch Institute’s (RKI) health monitoring system, as well as surveys from other research institutes and official statistics. In the future, the indicator set is to be developed further and integrated into an overall approach that is geared towards health reporting and the monitoring of chronic diseases in all phases of life.

Syria has been the main country of citizenship of refugees in Germany since 2013. Syrians face numerous human rights violations in their country that can be accompanied by the experience of potentially traumatic events, loss and displacement. Along the migration process, refugees are exposed to various factors that can have an impact on mental health. The aim of this study is to investigate sociodemographic, war- and flight-related as well as post-migration factors as predictors of posttraumatic stress, depression, somatization and anxiety in Syrian refugees with posttraumatic stress symptoms based in Germany. Data were based on the baseline sample of the “Sanadak” randomized-controlled trial. A total of 133 adult Syrian refugees participated in the study. A questionnaire covered sociodemographic and flight-related questions as well as standardized instruments for symptoms of PTSD (PDS-5), depression (PHQ-9), somatization (PHQ-15), anxiety (GAD-7), generalized self-efficacy (GSE), religiousness (Z-Scale), social support (ESSI) and mental health stigma (SSMIS-SF). Linear regression models were executed to predict mental health outcomes. Sociodemographic predictors (i.e., female sex, higher education) and flight-related predicting factors (i.e., variability of traumatic events) have a negative impact on mental health in Syrian refugees with posttraumatic stress symptoms in Germany. Mental health stigma predicts worse mental health outcomes. Post-migration factors have a major impact on mental health, such as low income, lack of social support, low life satisfaction or a strongly felt connection to Syria. Somatization is an important manifestation of mental distress in Syrian refugees with posttraumatic stress symptoms. Our study showed a range of factors predicting the mental health of Syrian refugees with posttraumatic stress symptoms. Measures to foster mental health could be securing financial security, promoting gender equality and tailored psychosocial programs addressing mental health stigma, loss and social support networks.

Abstract Background The prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life. Methods Participants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI). Results Results show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings. Conclusions Sufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

The role of genetic risk markers for Alzheimer’s disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundació ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-ε4 was significantly associated with the memory function NEs “delayed recall (DR)” (β = -0.76, p = 4.1 × 10-10), “learning” (β = -1.35, p = 2.91 × 10-6), and “recognition memory” (β = -0.58, p = 9.67 × 10-5); and with “DR” in the aMCI group (β = -0.36, p = 2.96 × 10-5). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-ε4 was also significantly associated with the NE “learning” in individuals classified as having Pss-aMCI (β = -1.37, p = 5.82 × 10-5). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the “backward digits” working memory NE (β = 0.52, p = 7.57 × 10-5) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE “repetition” (β = -0.19, p = 5.34 × 10-6). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Reported prevalence rates vary substantially between 1:500 (0.2%) and 1:3,000 (0.03%), which may be attributed to different study designs and population characteristics. Prevalence data for Germany is not available. Consequently, this study aimed (1) to quantify age- and gender-specific clinically diagnosed HCM prevalence in Germany based on the analysis of health care claims data of > 5 million insurants in 2015, and (2) to analyze temporal prevalence trends from 2011 to 2015.Data were extracted from the InGef (Insitute for Applied Health Research) database, which is an anonymized healthcare claims database with longitudinal data from patients insured in one of approximately 70 German social health insurances (SHIs). Patients were classified as HCM prevalent, if they had at least one verified ambulatory or one hospital main- or secondary discharge diagnosis of HCM (I42.1 or I42.2).In 2015, HCM was prevalent in 4,000 out of 5,490,810 patients (0.07%; 1:1,372). HCM prevalence increased gradually with age from 7.4/100,000 persons (95% CI 5.2-10.1) in 0-9 years old to 298.7/100,000 persons (95% CI 276.4-322.4) in patients > 80 years. In all age categories, men had a numerically higher prevalence than women with significant differences in patients > 30 years. There was a gradual annual prevalence increase from 75.8 (95% CI 75.2-76.4) in 2011 to 84.2 (95% CI 83.5-84.8) in 2015 per 100,000 persons.Overall, prevalence of clinically diagnosed HCM in Germany is lower than in systematic population studies based on echocardiographic diagnosis. Prevalence increased with advancing age and showed a constant yearly rise. Those observations may improve our understanding of the burden of this genetic heart disease on the health care system in Germany, increase the diagnostic awareness among clinicians and shape future screening and management strategies.

Abstract Background Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Results Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. Conclusions SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

For the treatment of depressive disorders, the framework of collaborative care has been recommended, which showed improved outcomes in the primary care sector. Yet, an earlier literature review did not find sufficient evidence to draw robust conclusions on the cost-effectiveness of collaborative care.To systematically review studies on the cost-effectiveness of collaborative care, compared with usual care for the treatment of patients with depressive disorders in primary care.A systematic literature search in major databases was conducted. Risk of bias was assessed using the Cochrane Collaboration's tool. Methodological quality of the articles was assessed using the Consensus on Health Economic Criteria (CHEC) list. To ensure comparability across studies, cost data were inflated to the year 2012 using country-specific gross domestic product inflation rates, and were adjusted to international dollars using purchasing power parities (PPP).In total, 19 cost-effectiveness analyses were reviewed. The included studies had sample sizes between n = 65 to n = 1,801, and time horizons between six to 24 months. Between 42% and 89% of the CHEC quality criteria were fulfilled, and in only one study no risk of bias was identified. A societal perspective was used by five studies. Incremental costs per depression-free day ranged from dominance to US$PPP 64.89, and incremental costs per QALY from dominance to US$PPP 874,562.Despite our review improved the comparability of study results, cost-effectiveness of collaborative care compared with usual care for the treatment of patients with depressive disorders in primary care is ambiguous depending on willingness to pay. A still considerable uncertainty, due to inconsistent methodological quality and results among included studies, suggests further cost-effectiveness analyses using QALYs as effect measures and a time horizon of at least 1 year.

ObjectiveThe objective of this study was to describe and analyze the effects of depression on health care utilization and costs in a sample of multimorbid elderly patients.MethodThis cross-sectional analysis used data of a prospective cohort study, consisting of 1,050 randomly selected multimorbid primary care patients aged 65 to 85 years. Depression was defined as a score of six points or more on the Geriatric Depression Scale (GDS-15). Subjects passed a geriatric assessment, including a questionnaire for health care utilization. The impact of depression on health care costs was analyzed using multiple linear regression models. A societal perspective was adopted.ResultsPrevalence of depression was 10.7%. Mean total costs per six-month period were €8,144 (95% CI: €6,199-€10,090) in patients with depression as compared to €3,137 (95% CI: €2,735-€3,538; pConclusionAmong multimorbid elderly patients, depression was associated with significantly higher health care utilization and costs. The effect of depression on costs was even greater than reported by previous studies conducted in less morbid patients.

The borderline personality disorder is a common mental disorder. It is frequently associated with various mental co-morbidities and a fundamental loss of functioning. The borderline personality disorder causes high costs to society. The aim of this study was to perform a systematic literature review of existing economic evaluations of treatments for borderline personality disorder.We performed a systematic literature search in MEDLINE, EMBASE, PsycINFO and NHSEED for partial and full economic evaluations regarding borderline personality disorder. Reported cost data were inflated to the year 2012 and converted into US-$ using purchasing power parities to allow for comparability. Quality assessment of the studies was performed by means of the Consensus on Health Economic Criteria checklist, a checklist developed by a Delphi method in cooperation with 23 international experts.We identified 6 partial and 9 full economic evaluations. The methodical quality was moderate (fulfilled quality criteria: 79.2% [SD: 15.4%] in partial economic evaluations, 77.3% [SD: 8.5%] in full economic evaluations). Most evaluations analysed psychotherapeutic interventions. Although ambiguous, most evidence exists on dialectical-behavioural therapy. Cognitive behavioural therapy and schema-focused therapy are cost-saving. Evidence on other interventions is scarce.The economic evidence is not sufficient to draw robust conclusions for all treatments. It is possible that some treatments are cost-effective. Most evidence exists on dialectical-behavioural therapy. Yet, it is ambiguous. Further research concerning the cost-effectiveness of treatments is necessary as well as the identification of relevant cost categories and the validation of effect measures.

BACKGROUND: Multimorbidity has a negative impact on health-related quality of life (HRQL). Previous studies included only a limited number of conditions. In this study, we analyse the impact of a large number of conditions on HRQL in multimorbid patients without preselecting particular diseases. We also explore the effects of these conditions on the specific dimensions of HRQL. MATERIALS AND METHODS: This analysis is based on a multicenter, prospective cohort study of 3189 multimorbid primary care patients aged 65 to 85. The impact of 45 conditions on HRQL was analysed. The severity of the conditions was rated. The EQ-5D, consisting of 5 dimensions and a visual-analogue-scale (EQ VAS), was employed. Data were analysed using multiple ordinary least squares and multiple logistic regressions. Multimorbidity measured by a weighted count score was significantly associated with lower overall HRQL (EQ VAS), b = -1.02 (SE: 0.06). Parkinson's disease had the most pronounced negative effect on overall HRQL (EQ VAS), b = -12.29 (SE: 2.18), followed by rheumatism, depression, and obesity. With regard to the individual EQ-5D dimensions, depression (OR = 1.39 to 3.3) and obesity (OR = 1.44 to 1.95) affected all five dimensions of the EQ-5D negatively except for the dimension anxiety/depression. Obesity had a positive effect on this dimension, OR = 0.78 (SE: 0.07). The dimensions "self-care", OR = 4.52 (SE: 1.37) and "usual activities", OR = 3.59 (SE: 1.0), were most strongly affected by Parkinson's disease. As a limitation our sample may only represent patients with at most moderate disease severity. CONCLUSIONS: The overall HRQL of multimorbid patients decreases with an increasing count and severity of conditions. Parkinson's disease, depression and obesity have the strongest impact on HRQL. Further studies should address the impact of disease combinations which require very large sample sizes as well as advanced statistical methods.

OBJECTIVE: To analyse predictors of costs in dementia from a societal perspective in a longitudinal setting. METHOD: Healthcare resource use and costs were assessed retrospectively using a questionnaire in four waves at 6-month intervals in a sample of dementia patients (N = 175). Sociodemographic data, dementia severity and comorbidity at baseline, cognitive impairment and impairment in basic and instrumental activities of daily living were also recorded. Linear mixed regression models with random intercepts for individuals were used to analyse predictors of total and sector-specific costs. RESULTS: Impairment in activities of daily living significantly predicted total costs in dementia patients, with associations between basic activities of daily living and formal care costs on the one and instrumental activities of daily living and informal care costs on the other hand. Nursing home residence was associated with lower total costs than residence in the community. There was no effect of cognition on total or sector-specific costs. CONCLUSION: Cognitive deficits in dementia are associated with costs only via their effect on the patients' capacity for activities of daily living. Transition into a nursing home may reduce total costs from a societal perspective, owing to the fact that a high amount of informal care required by severely demented patients prior to transition into a nursing home may cause higher costs than inpatient nursing care.