Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate

The serine/threonine kinase mammalian target of rapamycin (mTOR) governs growth, metabolism, and aging in response to insulin and amino acids (aa), and is often activated in metabolic disorders and cancer. Much is known about the regulatory signaling network that encompasses mTOR, but surprisingly few direct mTOR substrates have been established to date. To tackle this gap in our knowledge, we took advantage of a combined quantitative phosphoproteomic and interactomic strategy. We analyzed the insulin- and aa-responsive phosphoproteome upon inhibition of the mTOR complex 1 (mTORC1) component raptor, and investigated in parallel the interactome of endogenous mTOR. By overlaying these two datasets, we identified acinus L as a potential novel mTORC1 target. We confirmed acinus L as a direct mTORC1 substrate by co-immunoprecipitation and MS-enhanced kinase assays. Our study delineates a triple proteomics strategy of combined phosphoproteomics, interactomics, and MS-enhanced kinase assays for the de novo-identification of mTOR network components, and provides a rich source of potential novel mTOR interactors and targets for future investigation

Do self-reported hearing and visual impairments predict longitudinal dementia in older adults?

Background Sensory impairments have been associated with dementia in older adults. However, the contribution of different impairments and how they interact in the development of dementia is not clear. We examined the independent and interaction effects of hearing impairment (HI) and visual impairment (VI) on incident dementia. Design Multi-centric population-based prospective cohort study. Setting Data were taken from the AgeDifferent.de platform, pooling participants aged 75 and older from the German LEILA75+ and AgeCoDe/AgeQualiDe cohorts. Participants Older adults (N = 3497) with mean age 79.8 years, 67.2% female. Measurements Standardized interviews and questionnaires were used to assess self-reported HI and VI at baseline and all-cause dementia in 9 follow-ups, spanning over 20 years. Methods Competing risk regression models were conducted to test the main and interaction effects of HI and VI on dementia incidence, adjusting for established risk factors of dementia and accumulated mortality. Results HI and VI at baseline were reported by 30.3% and 16.6% of individuals, respectively. Adjusting for baseline information on sociodemographics, substance use, cognitive functioning and morbidity, and controlling for accumulated mortality risk, HI (sHR 1.16, 95% CI 1.04–1.30, p = 0.011) but not VI (sHR 1.07, 95% CI 0.90–1.28, p = 0.462) was significantly associated with incident dementia. There was no interaction between HI and VI (sHR 1.09, 95% CI 0.81–1.46, p = 0.567). Conclusions Hearing impairment is associated with an increased incidence of all-cause dementia in older adults. There is no excess risk or risk compensation through the additional presence or absence of visual impairment. Early prevention measures for hearing impairment might help to reduce the long-term risk of dementia

Prevalence of pain and its associated factors among the oldest-olds in different care settings – results of the AgeQualiDe study

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

Changes in Social Network Size Are Associated With Cognitive Changes in the Oldest-Old

Objectives:Social isolation is increasing in aging societies and several studies have shown a relation with worse cognition in old age. However, less is known about the association in the oldest-old (85+); the group that is at highest risk for both social isolation and dementia. Methods:Analyses were based on follow-up 5 to 9 of the longitudinal German study on aging, cognition, and dementia in primary care patients (AgeCoDe) and 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), a multi-center population-based prospective cohort study. Measurements included the Lubben Social Network Scale (LSNS-6), with a score below 12 indicating social isolation, as well as the Mini-Mental Status Examination (MMSE) as an indicator of cognitive function. Results:Dementia-free study participants (n = 942) were M = 86.4 (SD = 3.0) years old at observation onset, 68.2% were women. One third (32.3%) of them were socially isolated. Adjusted linear hybrid mixed effects models revealed significantly lower cognitive function in individuals with smaller social networks (β = 0.5, 95% CI = 0.3-0.7, p < .001). Moreover, changes in an individual's social network size were significantly associated with cognitive changes over time (β = 0.2, 95% CI = 0.1-0.4, p = .003), indicating worse cognitive function with shrinking social networks. Conclusion:Social isolation is highly prevalent among oldest-old individuals, being a risk factor for decreases in cognitive function. Consequently, it is important to maintain a socially active lifestyle into very old age. Likewise, this calls for effective ways to prevent social isolation

The Role of Social Isolation and the Development of Depression: A Comparison of the Widowed and Married Oldest Old in Germany

Widowhood is common in old age, can be accompanied by serious health consequences and is often linked to substantial changes in social network. Little is known about the impact of social isolation on the development of depressive symptoms over time taking widowhood into account. We provide results from the follow-up 5 to follow-up 9 from the longitudinal study AgeCoDe and its follow-up study AgeQualiDe. Depression was measured with GDS-15 and social isolation was assessed using the Lubben Social Network Scale (LSNS-6). The group was aligned of married and widowed people in old age and education through entropy balancing. Linear mixed models were used to examine the frequency of occurrence of depressive symptoms for widowed and married elderly people depending on the risk of social isolation. Our study shows that widowhood alone does not lead to an increased occurrence of depressive symptoms. However, "widowed oldest old", who are also at risk of social isolation, have significantly more depressive symptoms than those without risk. In the group of "married oldest old", women have significantly more depressive symptoms than men, but isolated and non-isolated do not differ. Especially for people who have lost a spouse, the social network changes significantly and increases the risk for social isolation. This represents a risk factor for the occurrence of depressive symptoms

Incidence of Anxiety in Latest Life and Risk Factors. Results of the AgeCoDe/AgeQualiDe Study

Research on anxiety in oldest-old individuals is scarce. Specifically, incidence studies based on large community samples are lacking. The objective of this study is to assess age- and gender-specific incidence rates in a large sample of oldest-old individuals and to identify potential risk factors. The study included data from N = 702 adults aged 81 to 97 years. Anxiety symptoms were identified using the short form of the Geriatric Anxiety Inventory (GAI-SF). Associations of potential risk factors with anxiety incidence were analyzed using Cox proportional hazard models. Out of the N = 702 older adults, N = 77 individuals developed anxiety symptoms during the follow-up period. The incidence rate was 51.3 (95% CI: 41.2–64.1) per 1000 person-years in the overall sample, compared to 58.5 (95% CI: 43.2–72.4) in women and 37.3 (95% CI: 23.6–58.3) in men. Multivariable analysis showed an association of subjective memory complaints (HR: 2.03, 95% CI: 1.16–3.57) and depressive symptoms (HR: 3.20, 95% CI: 1.46–7.01) with incident anxiety in the follow-up. Incident anxiety is highly common in late life. Depressive symptoms and subjective memory complaints are major risk factors of new episodes. Incident anxiety appears to be a response to subjective memory complaints independent of depressive symptoms

Frequency and gender differences in the use of professional home care in late life: Findings from three German old-age cohorts

Aim: The aim of this study was to investigate the frequency of and the gender differences in the use of professional home care in Germany. Methods: We used harmonized data from three large cohort studies from Germany (“Healthy Aging: Gender-specific trajectories into the latest life”; AgeDifferent.de Platform). Data were available for 5,393 older individuals (75 years and older). Mean age was 80.2 years (SD: 4.1 years), 66.6% were female. Professional homecare outcome variables were use of outpatient nursing care, paid household assistance, and meals on wheels’ services. Logistic regression models were used, adjusting for important sociodemographic variables. Results: Altogether 5.2% of older individuals used outpatient nursing care (6.2% women and 3.2% men; p < 0.001), 24.2% used paid household assistance (26.1% women and 20.5% men; p < 0.001) and 4.4% used meals on wheels’ services (4.5% women and 4.0% men; p = 0.49). Regression analysis revealed that women had higher odds of using paid household assistance than men (OR = 1.48, 95% CI: [1.24–1.76]; p < 0.001), whereas they had lower odds of using meals on wheels’ services (OR = 0.64, 95% CI: [0.42–0.97]; p < 0.05). No statistically significant differences in using outpatient nursing care between women and men were found (OR = 1.26, 95% CI: [0.87–1.81]; p = 0.225). Further, the use of home care was mainly associated with health-related variables (e.g., stroke, Parkinson’s disease) and walking impairments. Conclusions: Our study showed that gender differences exist in using paid household assistance and in culinary dependency. For example, meals on wheels’ services are of great importance (e.g., for individuals living alone or for individuals with low social support). Gender differences were not identified regarding outpatient nursing care. Use of professional home care servicesmay contribute to maintaining autonomy and independence in old age

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study

PurposeThe present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups.MethodsData were derived from a prospective multicenter cohort study conducted in primary care – the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up. To assess depressive symptoms, the short version of the Geriatric Depression Scale (GDS-15, cutoff score 6) was used. Age-specific competing risk regressions were performed to analyze risk factors for incident depressive symptoms in different age groups (75 to 79, 80 to 84, 85+ years), taking into account the accumulated mortality.ResultsThe age-specific incidence rate of depression was 33 (95% CI 29-38), 46 (95% CI 40-52) and 63 (95% CI 45-87) per 1,000 person years for the initial age groups 75 to 79, 80 to 84 and 85+ years, respectively. In competing risk regression models, female sex, mobility as well as vision impairment, and subjective cognitive decline (SCD) were found to be risk factors for incident depression for age group 75 to 79, female sex, single/separated marital status, mobility as well as hearing impairment, and SCD for age group 80 to 84, and mobility impairment for age group 85+.ConclusionDepressive symptoms in latest life are common and the incidence increases with increasing age. Modifiable and differing risk factors across the highest age groups open up the possibility of specifically tailored prevention concepts

Prevalence of Anxiety Symptoms and Their Association With Loss Experience in a Large Cohort Sample of the Oldest-Old. Results of the AgeCoDe/AgeQualiDe Study

Background: Anxiety in adults is a common mental health problem. However, studies on anxiety in the oldest-old are lacking. We sought to identify the age- and gender-specific prevalence of anxiety symptoms in a large sample of general practice patients. Furthermore, we investigated relevant associations of anxiety specifically with respect to recent experience of loss.Methods: Based on the German Study on Ageing, Cognition and Dementia in general practice patients, a sample of 897 patients aged 82 years and older was assessed. Anxiety was assessed using the short form of the Geriatric Anxiety Inventory (GAI-SF). For the assessment of loss, patients were asked whether there were cases of death in their closer social environment since the last assessment. Descriptive and logistic regression analyses were run.Results: Of the oldest-old individuals (aged 82+ years, mean age: 86.8), 14.5% (95% CI 12.4–16.8) suffered from anxiety symptoms. Highest prevalence rates were found for 82- to 85-year-old women (17.2%, 95% CI 12.6–22.1) and for 86- to 90-year-old patients (both sexes) in general (15.9%, 95% CI 12.6–19.2). Older individuals who experienced cases of death in their close social environment within the last 18 months had almost twice the odds [odds ratio (OR) 1.91, 95% confidence interval (CI) 1.15–3.17] of reporting anxiety compared to those without a recent loss. As expected, depression and impaired cognitive status were associated with the presence of anxiety symptoms. No relation was found between social network, gender, age, frailty, or physical illness and anxiety in regression analysis.Conclusions: This study provides for the first time age- and gender-specific prevalence rates of anxiety symptoms and associated risk factors among a large population-based sample of oldest-old primary care attenders. Anxiety is highly prevalent in individuals aged 82 years and older. Depression, impaired cognitive status, and recent experience of loss are associated with late-life anxiety. Our findings support the idea that recent experience of loss should be taken seriously in the context of clinical practice with respect to diagnosing and treating anxiety in old age

Regionale Standards: Ausgabe 2019

Die "Regionalen Standards" gehen zurück auf die Initiative eines gemeinsamen Arbeitskreises, bestehend aus Vertretern des Statistischen Bundesamtes, der Arbeitsgemeinschaft Sozialwissenschaftlicher Institute e.V. (ASI) und des ADM Arbeitskreis Deutscher Markt- und Sozialforschungsinstitute e.V. Sie stellen ein Angebot für die Forschung in der Bundesrepublik Deutschland dar. Die "Regionalen Standards" beschreiben Gebietsabgrenzungen und Instrumente zur Typisierung von Regionen, wie sie in der Bundesrepublik Deutschland von der amtlichen Statistik und/oder der Markt- und Sozialforschung in gewisser Regelmäßigkeit eingesetzt werden. Zusätzlich werden Datensätze aus unterschiedlichen Quellen vorgestellt, die für die Regionalisierung von Bevölkerungsumfragen genutzt werden können und für die Forschung (teils jedoch mit Einschränkungen) zur Verfügung stehen