OBJECTIVES:The demographic trend towards an ageing society is accompanied by an increase in age-related illnesses, with late-life depression (LLD) being one of the most common mental illnesses in the oldest-old (≥ 80 years). As activity participation potentially prevents LLD, this study examines sex-specific differences in the relationship between activity participation and LLD risk. METHOD:Data were derived from the prospective multicenter cohort study AgeCoDe/AgeQualiDe with 9 follow-ups (FU). LLD was assessed using the 15-item Geriatric Depression Scale (GDS-15, cut-off score 6). Activity participation was first assessed at FU1 based on 14 physical, social and cognitive activities (5-point ordinal scale). Statistical analyses included descriptive statistics, Mann-Whitney U-tests and Cox regressions estimating incident LLD from FU2 to FU9. Time at risk began at FU1, where activity participation was first assessed. RESULTS:Analyses included n = 2,305 at FU1; mean age 81.0; 64% women. Men reported significantly more physical activity (U = 569,468, p = 0.010), women more cognitive activity (U = 658,426, p = 0.002). A higher activity participation at FU1 was associated with a lower risk of LLD with HR = 0.97, 95% CI [0.95, 0.98]. Particularly, participation in physical activities reduced LLD risk with HR = 0.96, 95% CI [0.93, 0.98], which could not be shown for social and cognitive activities. Analyses could not confirm a sex-dependent association. CONCLUSION:Activity participation, especially in physical activities, appears preventive for LLD in the oldest-old. Contrary to the hypothesis, these associations did not differ between men and women.

INTRODUCTION:Dementia is associated with progressive impairments that increase the risks to driving safety. General practitioners (GPs) play an important role in initiating conversations about fitness to drive and in supporting people with dementia and their families. This integrative review asked how counseling on driving with dementia can be improved through needs-based interventions in general practice in Germany. METHODS:An integrative review was conducted. Using a predefined, highly sensitive search strategy, we searched seven bibliographic databases without time restrictions. Study selection, analysis, and interpretation were performed by a multiprofessional team. Studies in English and German were included. RESULTS:69 primary studies met the inclusion criteria and were analyzed. 39 quantitative studies, 24 qualitative studies, 3 studies using mixed methods, and 3 consensus and Delphi studies were included. Driving was viewed as important for maintaining autonomy and social participation by both people with dementia and family caregivers. Physician recommendation can be decisive in facilitating voluntary driving cessation. GPs reported concerns about straining the patient-physician relationship as a barrier to addressing driving safety. They also described feelings of uncertainty when assessing driving-relevant impairments and a need for communication and decision-support tools. Existing guidelines were perceived as too general and insufficiently tailored to the general practice setting. DISCUSSION AND CONCLUSION:International studies identified several intervention elements that facilitate talks about driving safety and driving cessation in primary care. In Germany, counseling in general practice should focus on early planning and ongoing support to maintain social participation and to address fears experienced by people with dementia.

Hintergrund Demenzerkrankungen führen zu erhöhten Risiken für die Fahrsicherheit. Hausärzt:innen kommt in der Ansprache und Begleitung der Fahrsicherheit bei Demenz eine große Bedeutung zu. Die Hauptfragestellung dieser Arbeit ist, wie die Beratung zum Thema Autofahren bei Demenz durch bedarfsorientierte Interventionen im Rahmen der hausärztlichen Versorgung in Deutschland verbessert werden kann. Methode Es wurde ein integrativer Review durchgeführt. Die Literatursuche erfolgte mit einer vorab festgelegten hochsensitiven Suchstrategie in sieben Literaturdatenbanken (MEDLINE, Embase, PsycINFO, Psyindex, Cochrane Library, CINAHL, BASE) ohne zeitliche Einschränkung. Einbezogen wurden Studien in englischer und deutscher Sprache. Ergebnisse 69 Primärstudien erfüllten die Einschlusskriterien und wurden in die Analyse eingeschlossen. Es wurden 39 quantitative Studien, 24 qualitative Studien, 3 Mixed-Methods-Studien und 3 Konsensus- und Delphi-Verfahren eingeschlossen. Die Studien zeigen, dass Menschen mit Demenz und ihre Angehörigen das Autofahren als bedeutsam für Autonomieerhalt und soziale Teilhabe bewerten. Für den freiwilligen Fahrverzicht kann die Empfehlung durch Ärzt:innen entscheidend sein. Als Barriere für die Ansprache der Fahrsicherheit wird von Hausärzt:innen die Sorge vor Belastung der Patient:innen-Ärzt:innen-Beziehung benannt. Auch bestehen Unsicherheiten bei der Einschätzung fahrsicherheitsrelevanter Einschränkungen und ein Bedarf an Kommunikations- und Entscheidungshilfen. Bestehende Leitlinien werden als zu allgemein und als nicht ausreichend auf das hausärztliche Setting zugeschnitten empfunden. Diskussion und Schlussfolgerung Aus internationalen Studien wurden verschiedene Interventionselemente zur Verbesserung der Ansprache von Fahrsicherheit und Fahrverzicht im primärärztlichen Setting identifiziert. Der Beratungsansatz für Hausarztpraxen in Deutschland liegt vor allem in der frühzeitigen Planung und Begleitung mit dem Ziel, soziale Teilhabe zu sichern und die Ängste und das Verlusterleben von Menschen mit Demenz zu adressieren.

INTRODUCTION:The polyunsaturated fatty acids (PUFAs) omega-6 (ω6) and omega-3 (ω3) are linked to cognitive performance and Alzheimer's-type dementia (DAT), but ω3-PUFA supplementation offers limited benefits. We propose that the ω6-PUFA/ω3-PUFA ratio better explains cognitive decline and DAT risk. METHODS:PUFA profiles were examined in the AgeCoDe cohort (n = 3327) and MAPT trial (n  = 1679). Cox and linear mixed models evaluated associations of individual PUFAs and the ω6-PUFA/ω3-PUFA ratio with DAT progression and cognitive decline. Mendelian randomization (MR) assessed genetic causal effects. The effect of ω3-PUFA on ω6-PUFA levels was analyzed. RESULTS:Higher ω6-PUFA/ω3-PUFA ratio increased DAT risk beyond ω3-PUFA levels alone. A baseline high (detrimental) ratio predicted faster cognitive decline, whereas longitudinal improvements slowed decline. MR supported a genetic non-causal link. Higher ω3-PUFA levels correlated with lower ω6-PUFA species. DISCUSSION:The ω6-PUFA/ω3-PUFA ratio better predicts cognitive decline and DAT progression than individual PUFAs, suggesting that dietary adjustments may help prevent dementia.

Listing tools were found to ameliorate drug treatment in older people; the FORTA (Fit-fOR-The-Aged) list is a clinically validated positive-negative list of medication appropriateness. Here, we retrospectively analyze longitudinal correlations between the FORTA score and key measures of physical and cognitive function in older people. 504 participants of a multi-center cohort study (AgeCoDe/AgeQualiDe) for whom the FORTA score (sum of over- and under-treatment errors) had been assessed were studied at three follow-up (FU) time points (FU 6–8; mean age range 87.9–89.7 years); comparisons between data at these FUs separated by 10 months were available for 292–328 patients. The univariate analysis of the association between FORTA_Delta_76 (change of FORTA score between FU 6 and 7) and ADL (Activities of Daily Living)_Delta_76 (− 0.155, p < 0.01) and between FORTA_Delta_76 and MMSE (Mini-Mental State Examination)_Delta_76 (− 0.203, p < 0.01) revealed significant correlations. Multivariable analysis (using a forward selection model, p < 0.05) revealed a significant association between FORTA_Delta_76 and MMSE_Delta_76 (p < 0.05). Univariate analyses for other comparisons were only significant for FORTA_Delta_86 and MMSE_Delta_86. This study indicates that longitudinal non-interventional changes of the FORTA score as an integral index of medication appropriateness are associated with changes in ADL and MMSE: the lower this score the better the functional outcome. These findings are in line with earlier interventional data and underscore the potential of FORTA to improve clinical endpoints in older people.

Abstract Background Medical assistants (MAs) are pivotal for access, coordination, and continuity in German primary care, yet workforce shortages and limited attention in research and policy persist. Prior studies quantify dissatisfaction and attrition drivers but offer little insight into how MAs who remain in practice experience job satisfaction. This study explores the social, personal and structural factors shaping MA job satisfaction in everyday work. Methods We conducted 14 semi-structured telephone interviews with MAs from German general practices (November–December 2023), recruited via the research networks, the professional association (VMF e.V.) and teaching practice lists. Interviews lasted approximately 60 min and the interview guide covered practice organisation, communication, working conditions, and job satisfaction. Interview data were analysed using a rapid qualitative analysis approach. Key statements were summarised in a structured matrix aligned with interview topics and compared across cases. Categories were developed iteratively through team-based analysis and consensus meetings, resulting in three overarching domains influencing job satisfaction: social (team dynamics and leadership), personal (identity and motivation), and structural (roles, pay, digital infrastructure, and staffing). Ethics approval: University of Duisburg-Essen, Medical Faculty (23-11354-BO; 14 Nov 2023). Participants provided written consent and received a €75 expense allowance. Results Three interrelated domains influenced job satisfaction. (1) Social (team dynamics/leadership): Experiences ranged from respectful, supportive leadership to inattentive or inconsistent supervision; structured feedback and clear communication reduced errors and strain, while gossip/bullying and informal word-of-mouth channels increased frustration. (2) Personal (identity/motivation): Satisfaction peaked when responsibilities matched training and skills were recognised and used. Emotional labour, especially in patient communication, was salient. Intrinsic motivation remained important, yet financial pressures increasingly shaped commitment. (3) Structural (roles, pay, digital, staffing): Continuing education (CE) was valued, but many courses were only minimally reflected in pay scales and CE gains were not consistently implemented in contracts or roles. Pay was widely perceived as inadequate relative to responsibility, particularly during the pandemic. Digital infrastructure was often unreliable, especially in rural areas. Understaffing and irregular breaks and overtime contributed to overload. Substitution with non-clinical staff was viewed critically for clinically consequential tasks. Discussion MA job satisfaction is co-produced by social, personal and structural conditions; the most salient burdens were emotional labour in patient contact and a misalignment between responsibility and compensation. Retention improves where leadership and communication routines are supportive, continuing education is translated into role/grade changes and visible use, and existing collective agreements are implemented consistently. Rather than new pay models, pragmatic fixes are needed, certificate-to-grade mapping, transparent role profiles, inflation-sensitive supplements, alongside dependable digital support. Delegation to non-clinical staff should exclude clinically consequential tasks (e.g. triage or telephone decisions). Conclusion MA job satisfaction in German primary care emerges from interacting social, personal and structural conditions. Targeted actions across these domains are needed to sustain workforce capacity and patient-centred care.

BACKGROUND:This article explores the psychological burden experienced by medical assistants (MAs) in General Practices during the Covid-19 pandemic (Corona virus disease 2019 (SARS-CoV-2)) in Germany. The study aims on demanding patient behavior, increased workload, and the perceived lack of appreciation and discuss their potential impact on the MAs´ well-being and career decisions. METHODS:A qualitative approach was utilized. MAs were included via a regional practice network as well as professional associations and newsletters. In total, 21 interviews with MAs from various federal states in Germany were conducted between April and September 2021. The semi-structured interview guideline focused on daily work challenges during the pandemic and its consequences. Interviews were recorded, transcribed, and analyzed using qualitative content analysis according to Kuckartz. RESULTS:The findings highlight core challenges, including demanding communication with patients, lack of appreciation in the media, a high workload, resilience versus career migration, and the needs and wishes of MAs in their everyday work. Abusive language, insults, and theft of materials by patients added significant stress. The interviews reveal how important teamwork and a supportive working environment are for overcoming these challenges. CONCLUSIONS:The study underlines the urgent need for societal and political awareness regarding the challenges faced by MAs, especially during public health crises. The perceived social egoism in patient behavior, coupled with a lack of recognition and appreciation, contributed to a challenging work atmosphere and potential burnout risk. Recommendations include enhancing support for MAs, recognizing their contributions in the media, and fostering collaborative efforts between practitioners and policymakers to address the unique challenges in general practices. TRIAL REGISTRATION:German Register of Clinical Studies (DRKS) DRKS00032402; https://drks.de/search/de/trial/DRKS00032402 (Registration Date: 14.08.2023).

BACKGROUND:Headaches are one of the most common symptoms worldwide. The majority of patients suffer from migraine. The prevalence of migraine is about 14% in the general population in industrialized countries. Its impact on primary care is high. Migraine is impairing and therefore a frequent and acute reason for consultation in primary care. Previous studies have attempted to derive the prevalence in the general population from a representative sample. Despite the importance of migraine, there is no data on its prevalence in general practitioner's (GP) practice. METHOD:This survey study of GPs in North Rhine Westphalia, Germany, presents the prevalence of patients with migraine in GP practices by asking GPs about the proportion of patients who present with their migraine. The headache frequency and incidence of these patients, as reported by GPs, were also surveyed. A questionnaire was designed according to methodological standards and sent to 362 GPs in North Rhine Westphalia. RESULTS:The questionnaire was answered in full by 49 GPs (response rate 13.5%). The GPs reported having spoken to 1,002 patients about their migraine within three months. This corresponded to a prevalence of 1.5% of all patients seen. Of these, 11.5% were severely affected patients with 8 to 14 (8.6%) or at least 15 (2.9%) headache days per month. CONCLUSIONS:The survey shows that around one tenth of the German general population suffering from migraine talk to their GP about their migraine. There is also a relevant proportion of one tenth of these patients who are severely affected by migraine. The GP practice offers a high and possibly underused potential to identify these patients, and offer them an adequate treatment option. In many cases, this could prevent the condition from becoming chronic.

Combining plasma phosphorylated Tau 217 (pTau217), with cognitive assessments allows for predicting incident dementia in mild cognitive impairment (MCI). However, the performance of this approach in primary care as well as the added value of other blood-based biomarkers (BBM) in this setting is unclear. We examined 833 older primary care patients from the AgeCoDe/AgeQualiDe study (median age=83). Plasma ALZpath pTau217 and other blood-based biomarkers (BBM; pTau181, GFAP, NfL, Abeta-42/40) were measured using single-molecule arrays. Subjective cognitive decline (SCD) and the Mini-Mental State Examination (MMSE) were assessed at baseline. We evaluated the performance of BBM, MMSE, and SCD reports for predicting the development of any cognitive impairment (MCI or dementia) or conversion to dementia at 3.5 and 7 years of follow-up using time-dependent ROC analysis with death as competing risk. Plasma pTau217 improved the prognosis of developing any cognitive impairment at follow-up beyond age, sex, and renal function (base model; Figure 1) and showed a high prognostic value at 7 years of follow-up (p<0.001, AUC=0.809; 3.5 years prognosis: p<0.001; AUC=0.767). Adding SCD and MMSE to the model provided only a small improvement in short-term prediction (3.5 years prognosis: p=0.002; AUC=0.785) while no significant improvements were observed by considering other BBM. For predicting incident dementia, pTau217 also increased the prognostic value beyond the base model (3.5 years: p=0.044, AUC=0.689; 7 years: p=0.002; AUC=0.697). However, this increase was smaller as compared to the prognosis of any cognitive impairment since individuals developing MCI but not dementia showed similar pTau217 levels at baseline. Furthermore, considering MMSE and SCD reports resulted in a considerable increase in prognostic value beyond pTau217 (3.5 years: p<0.001, AUC=0.791; 7 years: p=0.002; AUC=0.749). Plasma pTau217 in turn improved the long-term prediction beyond SCD reports and MMSE (p<0.001, AUC=0.749 vs 0.724). Again, other BBM did not increase the prognostic value. In our sample, pTau217 showed a high ability to discriminate between older primary care patients who will stay cognitively stable over seven years from patients developing any cognitive impairment, in contrast to other BBM. Assessments of SCD and cognition can further improve the identification of patients at increased short-term risk for dementia.

BACKGROUND:In the future, an increase in health care needs in the elderly is expected. Reports on unmet care needs of the oldest old with cognitive disorders are pending. This study aims at exploring unmet needs in the oldest old primary care patients with mild cognitive impairment (MCI) and dementia. Furthermore, the association between sociodemographic and clinical factors and unmet needs ought to be analyzed.METHODS:Based on the study "Needs, Health Service Use, Costs and Health-Related Quality of Life in a Large Sample of Oldest-Old Primary Care Patients (85+)" (AgeQualiDe), 749 patients (unimpaired, MCI, and dementia) aged 85 years and older, their relatives (n = 421), and general practitioners (GPs) (n = 607) were assessed. Descriptive, inferential, and regression analyses were run.RESULTS:Most unmet needs were observed in dementia patients, although needs were less frequently rated as unmet by dementia patients themselves as compared to relatives and GPs. Unmet needs were associated with MCI and dementia; other risk factors were age, education, and marital status.CONCLUSION:This study provides first data on unmet needs according to different perceptions in the elderly with MCI and dementia in Germany. Need assessments should be part of medical examinations to ensure a high-quality health care in the elderly.

Abstract Background Neurodegenerative disorders, including Alzheimer’s disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts. Methods DNA derived from post-mortem middle temporal gyrus (MTG) tissue from AD patients (n = 45) and age-matched controls (n = 35) was analyzed, along with DNA derived from blood samples from two independent cohorts: the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) cohort (n = 96) and the Dutch BioBank Alzheimer Center Limburg (BBACL) cohort (n = 262). Molecular profiling, including assessing mRNA expression and DNA (hydroxy)methylation levels, was conducted using HumanHT-12 v4 Expression BeadChip and HM 450 K BeadChip arrays, respectively. Functional interactions between genes and identification of common phenotype-specific positive and negative elementary circuits were conducted using computational modeling, i.e. gene regulatory network (GRN) and network perturbational analysis. DNA methylation of IDO2 (cg11251498) was analyzed using pyrosequencing. Results Twelve TRP- and twenty NAD-associated genes were found to be differentially expressed in the MTG of AD patients. Gene sets associated in the kynurenine pathway, the most common TRP pathway, and NAD pathway, showed enrichment at the mRNA expression level. Downstream analyses integrating data on gene expression, DNA (hydroxy)methylation, and AD pathology, as well as GRN and network perturbation analyses, identified IDO2, an immune regulatory gene, as a key candidate in AD. Notably, one CpG site in IDO2 (cg11251498) exhibited significant methylation differences between AD converters and non-converters in the AgeCoDe cohort. Conclusion These findings reveal substantial transcriptional and epigenetic alterations in TRP- and NAD-pathway-associated genes in AD, highlighting IDO2 as a key candidate gene for further investigation. These genes and their encoded proteins hold potential as novel biomarkers and therapeutic targets for AD.

BACKGROUND:Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts. METHODS:DNA derived from post-mortem middle temporal gyrus (MTG) tissue from AD patients (n = 45) and age-matched controls (n = 35) was analyzed, along with DNA derived from blood samples from two independent cohorts: the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) cohort (n = 96) and the Dutch BioBank Alzheimer Center Limburg (BBACL) cohort (n = 262). Molecular profiling, including assessing mRNA expression and DNA (hydroxy)methylation levels, was conducted using HumanHT-12 v4 Expression BeadChip and HM 450 K BeadChip arrays, respectively. Functional interactions between genes and identification of common phenotype-specific positive and negative elementary circuits were conducted using computational modeling, i.e. gene regulatory network (GRN) and network perturbational analysis. DNA methylation of IDO2 (cg11251498) was analyzed using pyrosequencing. RESULTS:Twelve TRP- and twenty NAD-associated genes were found to be differentially expressed in the MTG of AD patients. Gene sets associated in the kynurenine pathway, the most common TRP pathway, and NAD pathway, showed enrichment at the mRNA expression level. Downstream analyses integrating data on gene expression, DNA (hydroxy)methylation, and AD pathology, as well as GRN and network perturbation analyses, identified IDO2, an immune regulatory gene, as a key candidate in AD. Notably, one CpG site in IDO2 (cg11251498) exhibited significant methylation differences between AD converters and non-converters in the AgeCoDe cohort. CONCLUSION:These findings reveal substantial transcriptional and epigenetic alterations in TRP- and NAD-pathway-associated genes in AD, highlighting IDO2 as a key candidate gene for further investigation. These genes and their encoded proteins hold potential as novel biomarkers and therapeutic targets for AD.

Introduction After being diagnosed with dementia, patients need a medical professional to empathetically address their fears and get initial questions answered. This scoping review therefore addresses how patients newly diagnosed with dementia are cared for in the general practitioner (GP) setting and how the communication between different healthcare professionals and the GP is handled. Methods The scoping review was conducted based on the PRISMA Extension for Scoping Reviews checklist. After developing a search algorithm, literature searches were performed in PubMed, Scopus, Web of Science, Cochrane Library, PsychInfo, GeroLit and Cinahl using defined search criteria, such as a focus on qualitative study designs. After the removal of duplicates, title/abstract and full text screening was carried out. Results Final data extraction included 10 articles out of 12,633 records. Strategies regarding the post-acute care of newly diagnosed patients included providing clarity and comfort to the patients and giving support and information both pre- and post-diagnosis. Care efforts were focused on advanced care planning and deprescribing. Involving people with dementia and their caregivers in further care was seen as crucial to provide them with the support needed. GPs emphasised the importance of listening to concerns, as well as ensuring wishes are respected, and autonomy is maintained. All studies found communication between the GP setting and other healthcare professionals regarding post-acute care to be inadequate. Lack of information sharing, clinical notes and recommendations for the GP setting resulted in inefficient provision of support, as GPs feel limited in their ability to act. Discussion Sharing necessary information with the GP setting could promote patient-centred care for people living with dementia and facilitate appropriate and timely resource allocation and effective healthcare collaboration between the settings, for example, by defining clear care pathways and clarifying roles and expectations.

Purpose The present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups.Methods Data 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.Results The 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+.Conclusion Depressive 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.

BackgroundPrimary care research networks can generate important information in the setting where most patients are seen and treated. However, this requires a suitable IT infrastructure (ITI), which the North Rhine-Westphalian general practice research network is looking to implement. ObjectiveThis mixed methods research study aims to evaluate (study 1) requirements for an ITI and (study 2) the usability of an IT solution already available on the market, the FallAkte Plus (FA+) system for the North Rhine-Westphalian general practice research network, which comprises 8 primary care university institutes in Germany’s largest state. MethodsIn study 1, a survey was conducted among researchers from the institutes to identify the requirements for a suitable ITI. The questionnaire consisted of standardized questions with open-ended responses. In study 2, a mixed method approach combining a think-aloud approach and a quantitative survey was used to evaluate the usability and acceptance of the FA+ system among 3 user groups: researchers, general practitioners, and practice assistants. Respondents were asked to assess the usability with the validated system usability scale and to test a short questionnaire on vaccination management through FA+. ResultsIn study 1, five of 8 institutes participated in the requirements survey. A total of 32 user requirements related primarily to study management were identified, including data entry, data storage, and user access management. In study 2, a total of 36 participants (24 researchers and 12 general practitioners or practice assistants) were surveyed in the mixed methods study of an already existing IT solution. The tutorial video and handouts explaining how to use the FA+ system were well received. Researchers, unlike practice personnel, were concerned about data security and data protection regarding the system’s emergency feature, which enables access to all patient data. The median overall system usability scale rating was 60 (IQR 33.0-85.0), whereby practice personnel (median 82, IQR 58.0-94.0) assigned higher ratings than researchers (median 44, IQR 14.0-61.5). Users appreciated the option to integrate data from practices and other health care facilities. However, they voted against the use of the FA+ system due to a lack of support for various study formats. ConclusionsUsability assessments vary markedly by professional group and role. In its current stage of development, the FA+ system does not fully meet the requirements for a suitable ITI. Improvements in the user interface, performance, interoperability, security, and advanced features are necessary to make it more effective and user-friendly. Collaborating with end users and incorporating their feedback are crucial for the successful development of any practice network research ITI.

Listing tools have been developed to improve medications in older patients, including the Fit fOR The Aged (FORTA) list, a clinically validated, positive-negative list of medication appropriateness. Here, we aim to validate MyFORTA, an automated tool for individualized application of the FORTA list. 331 participants of a multi-center cohort study (AgeCoDe) for whom the FORTA score (sum of overtreatment and undertreatment errors) had been determined manually (gold standard [GS]) were reassessed using the automated MyFORTA (MF) tool. This tool determines the score from ATC and ICD codes combined with clinical parameters. The FORTA scores were 9.01 ± 2.91 (mean ± SD, MF) versus 6.02 ± 2.52 (GS) (p < 0.00001). Removing undertreatment errors for calcium/vitamin D (controversial guidelines) and influenza/pneumococcal vaccinations (no robust information in the database), the difference decreased: 7.5 ± 2.7 (MF) versus 5.98 ± 2.55 (GS) (p < 0.00001). The remaining difference was driven by, for example, missing nitro spray in coronary heart disease/acute coronary syndrome as the related information was rarely found in the database, but notoriously detected by MF. Three hundred and forty errors from those 100 patients with the largest score deviation accounted for 68

Introduction About 49% of the women in Germany take part in the German national mammography screening program. Reasons (not) to participate are still not well understood.Materials and methods Women were recruited from the participants of a former questionnaire study on the same issue. Considering their willingness to participate (6 yes, 2 no), level of education (6 high, 2 low) and confidence in their decision-making (6 high, 2 low), 8 women were selected and questioned in 2014 individually in problem-centered interviews. Sequences of the interview transcripts were evaluated by a multidisciplinary team using the content analysis approach.Results All 8 women had undergone mammography before. Analysis identified six overarching categories: sense of duty, autonomy, doubt, uncertainty, role of the physician, institutional setting. The women perceived screening as a chance to avoid the risk of being affected by breast cancer. Experience with breast cancer in their family or acquaintances influenced their decision. They put great emphasis on self-determination, but on the other hand they followed the advice of their trusted physician. During the screening procedure, they felt that they were exposed to an impersonal procedure that was painful.Conclusion Women tend to decide to participate in mammography screening on the emotional level. To enable women the opportunity to make an informed consent/refusal to mammography screening, physicians should discuss women's perceptions and experiences, and also provide factual information.

Blood-based biomarkers offer a major benefit to Alzheimer’s disease screening because they are less invasive and costly than cerebrospinal fluid or imaging biomarkers, but they have been mainly studied in individuals from memory clinics often exhibiting only mild comorbidities. Therefore, it is necessary to validate plasma biomarkers in more heterogeneous population-based studies to transfer these results to the general population. Plasma levels of Aβ42/Aβ40, P-tau181, NfL, and GFAP were measured using Single molecule array (Simoa) technology in samples from 1007 non-demented participants from the longitudinal population-based German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). Participants had a median age of 83 years old and were followed for up to 8 years. We evaluated the association of plasma biomarkers with risk of progression to dementia of the Alzheimer’s type (DAT) and cognitive decline using Cox regressions and linear mixed-effects models, and their capacity to discriminate between non-converters and DAT-converters with logistic regressions. Cox regressions adjusted for age and sex in non-demented participants indicated that higher levels of P-tau181 (HR = 1.32, p = 2.14×10 −5 ), NfL (HR = 1.15, p = 0.03), and GFAP (HR = 1.33, p = 2.55×10 −7 ), and a lower Aβ42/Aβ40 ratio (HR = 0.83, p = 0.02) were associated with a higher risk of progression to DAT. In addition, higher plasma levels of P-tau181 ( p = 3.05×10 −4 ), NfL ( p = 0.04), and GFAP ( p = 2.78×10 −7 ) were associated with faster cognitive decline, but no association was found with plasma Aβ42/Aβ40 ratio ( p = 0.24). When evaluated separately, plasma biomarkers displayed a rather low AUC at different time points (2, 4, 6, 8 years from baseline; AUC < 0.7) to discriminate between non-converters and DAT-converters. However, when combined into a single prediction model, plasma biomarkers substantially improved the discrimination capacity beyond demographics and APOE genotype within a 6-year period (AUC base model = 0.66, AUC biomarkers model = 0.72, DeLong’s test: p = 0.01). Plasma biomarkers are associated with progression to DAT in non-demented participants. Assessing multiple plasma biomarkers will considerably improve risk assessment for progressing to DAT in primary care.

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer’s dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

The gut microbiome may be involved in the occurrence of dementia primarily through the molecular mechanisms of producing bioactive molecules and promoting inflammation. Epidemiological evidence linking gut microbiome molecules and inflammatory markers to dementia risk has been mixed, and the intricate interplay between these groups of biomarkers suggests that their joint investigation in the context of dementia is warranted. We aimed to simultaneously investigate the association of circulating levels of selected gut microbiome molecules and inflammatory markers with dementia risk. This case-cohort epidemiological study included 805 individuals (83 years, 66% women) free of dementia at baseline. Plasma levels of 19 selected gut microbiome molecules comprising lipopolysaccharide, short-chain fatty acids, and indole-containing tryptophan metabolites as well as four inflammatory markers measured at baseline were linked to incident all-cause (ACD) and Alzheimer's disease dementia (AD) in binary outcomes and time-to-dementia analyses. Independent of several covariates, seven gut microbiome molecules, 5-hydroxyindole-3-acetic acid, indole-3-butyric acid, indole-3-acryloylglycine, indole-3-lactic acid, indole-3-acetic acid methyl ester, isobutyric acid, and 2-methylbutyric acid, but no inflammatory markers discriminated incident dementia cases from non-cases. Furthermore, 5-hydroxyindole-3-acetic acid (hazard ratio: 0.58; 0.36-0.94, P = 0.025) was associated with time-to-ACD. These molecules underpin gut microbiome-host interactions in the development of dementia and they may be crucial in its prevention and intervention strategies. Future larger epidemiological studies are needed to confirm our findings, specifically in exploring the repeatedly measured circulating levels of these molecules and investigating their causal relationship with dementia risk.