A meta-analysis of genome-wide studies of resilience in the German population.

Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10-8), but suggested five genomic loci (p < 1 × 10-5). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10-6) and 32 potential candidates (p < 1 × 10-4). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience's relationship with other personality traits and mental health.

Profiles of met and unmet care needs in the oldest-old primary care patients with cognitive disorders and dementia - results of the AgeCoDe and AgeQualiDe study.

INTRODUCTION: The prevalence of MCI and dementia is increasing as the oldest-old population grows, requiring a nuanced understanding of their care needs. Few studies have examined need profiles of oldest-old patients with MCI or dementia. Therefore, this study aims to identify patients' need profiles. METHODS: The data analysis included cross-sectional baseline data from N = 716 primary care patients without cognitive impairment (n = 575), with MCI (n = 97), and with dementia (n = 44) aged 85+ years from the multicenter cohort AgeQualiDe study "Needs, Health Service Use, Costs and Health-Related Quality of Life in a Large Sample of Oldest-Old Primary Care Patients [85+]". Patients' needs were assessed using the Camberwell Assessment of Need for the Elderly (CANE), and latent class analysis identified need profiles. Multinomial logistic regression analyzed the association of MCI and dementia with need profiles, adjusting for sociodemographic factors, social network (Lubben Social Network Scale, LSNS-6), and frailty (Clinical Frailty Scale, CSHA-CFS). RESULTS: Results indicated three profiles: 'no needs', 'met physical and environmental needs', and 'unmet physical and environmental needs'. MCI was associated with the met and unmet physical and environmental needs profiles; dementia was associated with the unmet physical and environmental needs profile. Patients without MCI or dementia had larger social networks (LSNS-6). Frailty was associated with dementia. CONCLUSIONS: Integrated care should address the needs of the oldest-old and support social networks for people with MCI or dementia. Assessing frailty can help clinicians to identify the most vulnerable patients and develop beneficial interventions for cognitive disorders.

Development, validation and application of an LC-MS/MS method quantifying free forms of the micronutrients queuine and queuosine in human plasma using a surrogate matrix approach.

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside exclusively synthesized by bacteria. This micronutrient and its respective nucleobase form queuine (q) are salvaged by humans either from gut microflora or digested food. Depletion of Q-tRNA in human or mouse cells causes protein misfolding that triggers endoplasmic reticular stress and the activation of the unfolded protein responses. In vivo, this reduces the neuronal architecture of the mouse brain affecting learning and memory. Herein, a sensitive method for quantifying free q and Q in human blood was developed, optimised and validated. After evaluating q/Q extraction efficiency in several different solid-phase sorbents, Bond Elut PBA (phenylboronic acid) cartridges were found to have the highest extraction recovery for q (82%) and Q (71%) from pooled human plasma. PBS with 4% BSA was used as surrogate matrix for method development and validation. An LC-MS/MS method was validated across the concentration range of 0.0003-1 µM for both q and Q, showing excellent linearity (r2 = 0.997 (q) and r2 = 0.998 (Q)), limit of quantification (0.0003 µM), accuracy (100.39-125.71%) and precision (CV% < 15.68%). In a sampling of healthy volunteers (n = 44), there was no significant difference in q levels between male (n = 14; mean = 0.0068 µM) and female (n = 30; mean = 0.0080 µM) participants (p = 0.50). Q was not detected in human plasma. This validated method can now be used to further substantiate the role of q/Q in nutrition, physiology and pathology.

The effect of depressive symptoms on quality of life and its different facets in the oldest age population: evidence from the AgeQualiDe prospective cohort study.

PURPOSE: The present study aims to investigate the prospective effect of depressive symptoms on overall QoL in the oldest age group, taking into account its different facets. METHODS: Data were derived from the multicenter prospective AgeCoDe/AgeQualiDe cohort study, including data from follow-up 7-9 and n = 580 individuals 85 years of age and older. Overall QoL and its facets were assessed using the WHOQOL-OLD instrument. The short form of the geriatric depression scale (GDS-15) was applied to assess depressive symptoms. Cognitively impaired individuals were excluded. Linear mixed-effects models were used to assess the effect of depressive symptoms on QoL. RESULTS: Depressive symptoms were significantly associated with overall QoL and each of the different facets of WHOQOL-OLD, also after adjustment for time and sociodemographic characteristics such as age, gender, education, marital status, living situation, and cognitive status. Higher age and single as well as divorced marital status were also associated with a lower QoL. CONCLUSION: This work provides comprehensive longitudinal results on the relationship between depressive symptoms and QoL in the oldest age population. The results underscore the relevance of tailored and targeted care planning and the development of customized interventions.

Predictors of dementia among the oldest old: longitudinal findings from the representative "survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)".

BACKGROUND/AIMS: Our current study aimed to investigate the determinants of dementia among the oldest old using longitudinal data from a representative sample covering both community-dwelling and institutionalized individuals. METHODS/DESIGN: Longitudinal representative data were taken from the "Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)" that surveyed community-dwelling and institutionalized individuals aged 80 years and above (n = 1,296 observations in the analytic sample), living in North Rhine-Westphalia (most populous state of Germany). The established DemTect was used to measure cognitive impairment (i.e., probable dementia). A logistic random effects model was used to examine the determinants of probable dementia. RESULTS: The mean age was 86.3 years (SD: 4.2 years). Multiple logistic regressions revealed that a higher likelihood of probable dementia was positively associated with lower education (e.g., low education compared to medium education: OR: 3.31 [95% CI: 1.10-9.98]), a smaller network size (OR: 0.87 [95% CI: 0.79-0.96]), lower health literacy (OR: 0.29 [95% CI: 0.14-0.60]), and higher functional impairment (OR: 13.45 [3.86-46.92]), whereas it was not significantly associated with sex, age, marital status, loneliness, and depressive symptoms in the total sample. Regressions stratified by sex were also reported. DISCUSSION: Our study identified factors associated with dementia among the oldest old. This study extends current knowledge by using data from the oldest old; and by presenting findings based on longitudinal, representative data (also including individuals residing in institutionalized settings). CONCLUSIONS: Efforts to increase, among other things, formal education, network size, and health literacy may be fruitful in postponing dementia, particularly among older women. Developing health literacy programs, for example, may be beneficial to reduce the burden associated with dementia.

Behind the times? Associations of working-time autonomy with health-related and occupational outcomes in health care personnel- a latent profile analysis.

BACKGROUND: In the light of personnel shortage, the health care sector is facing the challenge to combine increasing employees' as well as patients' needs. The aim of this study was to investigate the association between working-time autonomy and health-related (fatigue, psychosomatic complaints and work ability), as well as occupational outcomes (job satisfaction and turnover intention) in a large sample of health care employees. METHOD: Based on data of the BauA-Working Time survey, a sample of n = 1,093 employees working in the health care sector was analysed. Outcomes were assessed by the German Fatigue Scale, the Work Ability-Index and single-item measurements. Besides descriptive analyses, latent profile analysis (LPA) was used to determine clusters of employees based on working-time autonomy. Subsequently, regression analyses have been conducted to examine the association between autonomy clusters with health-related and occupational outcomes, controlling for sociodemographic characteristics and employment status. RESULTS: LPA revealed that a three-cluster model was most suitable: high autonomy (cluster 1), medium autonomy (cluster 2) and low autonomy (cluster 3). The extracted profiles of working-time autonomy differed significantly in terms of sociodemographic and occupational characteristics, but not in terms of average working hours per week or monthly household income. The multivariate regression analysis revealed that being in the low-autonomy cluster was associated with more psychosomatic health complaints (IRR: 1.427, p = 0.008), lower work ability (OR 0.339, p < 0.001), as well as less job satisfaction (OR 0.216, p < 0.001). DISCUSSION: Overall, the analyses indicate that it is crucial to prospectively consider working-time autonomy as an important factor of satisfaction, well-being and turnover intention in health care employees.

Associations between person-environment fit and mental health - results from the population-based LIFE-Adult-Study.

Within occupational settings, mental health of employees can be affected by complex interactions between individuals and their work environment. The aim of this cross-sectional analysis was to investigate the association between person-environment fit and mental health in employees. Data of n = 568 participants from the LIFE adult cohort study was analysed, including socio-demographic characteristics, three dimensions of person-environment fit (P-E fit), symptoms of depression and anxiety. Assessment took place between 2017 and 2021. Statistical analysis included descriptive analyses as well as generalized linear regression models adjusted for age, gender, socioeconomic status, marital status, and job status. Correlational analysis revealed significant associations between age, marital status, SES, employment status, symptoms of depression and anxiety and P-E fit. According to regression models, greater perceived fit between person and organization was associated with lower depression scores and lower symptoms of anxiety. Higher perceived fit between demands and abilities was significantly related to lower severity of depression and anxiety. Similarly, participants reporting a higher fit between needs and supplies, exhibited less symptom severity regarding depression and anxiety. These results underline the importance of person-environment fit regarding mental health. Finding ways to obtain an optimal balance should not only be recognized as an important factor for health and well-being, but might also be beneficial for organizations and employers in the long-term.

Quality over quantity - rethinking social participation in dementia prevention: results from the AgeWell.de trial.

BACKGROUND: Social participation as a protective factor against cognitive decline was one of the targets in the AgeWell.de study, a multi-domain interventional trial in a sample of older adults at increased risk for dementia. This study aimed to examine differential effects of the intervention and other influencing factors on social participation throughout the trial. METHODS: A longitudinal analysis of study data at the primary follow-up after 24 months (n = 819) was conducted. The Lubben Social Network Scale (LSNS-6) was used to assess quantitative aspects of social networks, and self-reported social activities were classified using a three-tiered categorical framework to capture qualitative aspects. RESULTS: A positive effect of the intervention was observed at the qualitative framework level, with an OR of 1.38 [95% CI: 1.05-1.82] for achieving or maintaining higher social participation at follow-up, while no effect could be detected on quantitative social network characteristics. Later phases of the Covid-19 pandemic showed a negative impact on the level of social participation at follow-up with an OR of 0.84 [95% CI: 0.75-0.95]. CONCLUSIONS: These findings suggest that by focusing on qualitative aspects of social participation as a component of dementia prevention, future interventions can promote enriched social interactions within established social networks. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) ID DRKS00013555.

Motivation to work and attitudes towards retirement among physicians.

BACKGROUND: The healthcare system is currently in a state of tension due to a shortage of physicians, the early retirement of health care professionals and an increasing need for care within an (aging) society. Therefore, the aim of the present study was to examine physicians' attitudes towards retirement and possible influencing factors on their motivation to work. METHOD: Data were collected as part of a baseline survey of a long-term study. The sample includes a variety of physicians (n = 625), working in outpatient or inpatient care, who have not yet reached the retirement age of 67. The primary outcome was to survey attitudes towards retirement using the Motivation to Work scale. Work-related characteristics (e.g., with regard to contract or working hour) as well as job satisfaction, overall health, and burnout were also included in the analyses (correlations and linear regression models). RESULTS: According to the results, sociodemographic characteristics are not significantly related to motivation to work, whereas the other parameters (satisfaction, health, and burnout) influence attitudes towards retirement significantly. CONCLUSIONS: The results underline the need to improve the occupational conditions of physicians across different medical settings. More research is needed to understand physicians' decision-making with regard to retirement, especially in terms of work-related characteristics and differences.

Potential for reducing dementia risk: association of the CAIDE score with additional lifestyle components from the LIBRA score in a population at high risk of dementia.

OBJECTIVES: Various dementia risk scores exist that assess different factors. We investigated the association between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score and modifiable risk factors in the Lifestyle for Brain Health (LIBRA) score in a German population at high risk of Alzheimer's disease. METHOD: Baseline data of 807 participants of AgeWell.de (mean age: 68.8 years (SD = 4.9)) were analysed. Stepwise multivariable regression was used to examine the association between the CAIDE score and additional risk factors of the LIBRA score. Additionally, we examined the association between dementia risk models and cognitive performance, as measured by the Montreal Cognitive Assessment. RESULTS: High cognitive activity (ß = -0.016, p < 0.001) and high fruit and vegetable intake (ß = -0.032, p < 0.001) correlated with lower CAIDE scores, while diabetes was associated with higher CAIDE scores (ß = 0.191; p = 0.032). Although all were classified as high risk on CAIDE, 31.5% scored ≤0 points on LIBRA, indicating a lower risk of dementia. Higher CAIDE and LIBRA scores were associated with lower cognitive performance. CONCLUSION: Regular cognitive activities and increased fruit and vegetable intake were associated with lower CAIDE scores. Different participants are classified as being at-risk based on the dementia risk score used.