Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease.

BACKGROUND: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. OBJECTIVE: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. METHODS: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. RESULTS: All individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA. CONCLUSIONS: We here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Introducing a machine learning algorithm for delirium prediction-the Supporting SURgery with GEriatric Co-Management and AI project (SURGE-Ahead).

INTRODUCTION: Post-operative delirium (POD) is a common complication in older patients, with an incidence of 14-56%. To implement preventative procedures, it is necessary to identify patients at risk for POD. In the present study, we aimed to develop a machine learning (ML) model for POD prediction in older patients, in close cooperation with the PAWEL (patient safety, cost-effectiveness and quality of life in elective surgery) project. METHODS: The model was trained on the PAWEL study's dataset of 878 patients (no intervention, age ≥ 70, 209 with POD). Presence of POD was determined by the Confusion Assessment Method and a chart review. We selected 15 features based on domain knowledge, ethical considerations and a recursive feature elimination. A logistic regression and a linear support vector machine (SVM) were trained, and evaluated using receiver operator characteristics (ROC). RESULTS: The selected features were American Society of Anesthesiologists score, multimorbidity, cut-to-suture time, estimated glomerular filtration rate, polypharmacy, use of cardio-pulmonary bypass, the Montreal cognitive assessment subscores 'memory', 'orientation' and 'verbal fluency', pre-existing dementia, clinical frailty scale, age, recent falls, post-operative isolation and pre-operative benzodiazepines. The linear SVM performed best, with an ROC area under the curve of 0.82 [95% CI 0.78-0.85] in the training set, 0.81 [95% CI 0.71-0.88] in the test set and 0.76 [95% CI 0.71-0.79] in a cross-centre validation. CONCLUSION: We present a clinically useful and explainable ML model for POD prediction. The model will be deployed in the Supporting SURgery with GEriatric Co-Management and AI project.

A 10-step participatory program for developing, implementing, and evaluating physical activity promoting actions in nursing homes in Germany.

BACKGROUND: Since multidimensional barriers challenge nursing homes, a socio-ecological approach is needed for physical activity promotion in this setting. So far, little is known about how such an approach can be transferred into the successful development and implementation of PA-promoting actions together with stakeholders on-site. We aimed to investigate the actions and dimensions of PA-promoting actions and their sustainable implementation. To contribute to closing this gap, we present a 10-step program for co-developing and co-evaluating PA-promoting actions in nursing homes through an integrated counselling approach. METHODS: We used a multiple case study approach that built upon manifold data sources, collected in 7 nursing homes over 3 years between 2021 and 2023. We collected fieldnotes and photologs from 14 future workshops (2 per home); 7 evaluation workshops (1 per home); 36 individual counsellings (2 sessions per resident), as well as 87 implementation protocols (action type and frequency), 11 evaluation questionnaires (changes among resources, cooperations, and collaborations); 7 goal attainment scales and 18 individual activity schedules. In addition, we retrieved and documented progress information at regular intervals by phone or email. RESULTS: With staff, residents, relatives, and volunteers, we co-developed 112 ideas for PA promotion; from which 54 ideas were implemented and integrated into everyday life, differentiated into "activities of daily living," "structured activities," and "activity-friendly environments."; 18 residents in 4 homes participated in individual counselling to develop individual activity schedules. Eighteen actions were rated as "(much) more successful than expected"; 10 "(much) worse than expected," and 23 "as successful as expected." Three actions were not evaluated. DISCUSSION: The participatory integrated counselling approach led to home-specific actions and promoted implementation into everyday life. The number and dimensions of actions implemented largely depended on the mission and vision of the respective home. The lack of staff could partially be compensated for by involving neighbourhoods, volunteers, and community organisations, such as local clubs. CONCLUSION: To effectively promote PA in nursing homes, a tailored approach considering structural conditions, locations, volunteer engagement, and organisational visions is essential. Long-lasting partnerships and low-threshold opportunities prove promising. Future research should delve into structural-level change processes and outcomes in this context.

Physical Activity, Sedentary Behavior, and Their Predictors Among Nursing Home Residents-Cross-Sectional Results of the BaSAlt Study.

Little is known about physical activity (PA) and sedentary behavior (SB) among nursing home residents although PA is known as a health promoter. This study examined PA, SB, and their predictors among nursing home residents (n = 63). Dependent variables were accelerometry-based PA and SB. Predictor variables included in a path analysis were age, sex, body mass index, Barthel Index, cognitive status (Mini-Mental State Examination), physical performance (hand grip strength and habitual walking speed), and well-being (World Health Organization-5 well-being index). PA was very low (M steps per day = 2,433) and SB was high (M percentage of sedentary time = 89.4%). PA was significantly predicted by age (ß = -0.27, p = .008), body mass index (ß = -0.29, p = .002), Barthel Index (ß = 0.24, p = .040), and hand grip strength (ß = 0.30, p = .048). SB was significantly predicted by body mass index (ß = 0.27, p = .008) and Barthel Index (ß = -0.30, p = .012). Results might be helpful for everyday practice to identify individuals at high risk for low PA and high SB.

[Sarcopenia, physical activity and sedentary behavior among nursing home residents in Germany]. / Sarkopenie, körperliche Aktivität und sedentäres Verhalten von Pflegeheimbewohnenden in Deutschland.

BACKGROUND: Residents in nursing homes show a high prevalence of the musculoskeletal syndrome sarcopenia and tend not to achieve current physical activity recommendations. OBJECTIVE: The aim of this study is to identify differences in physical activity and sedentary behavior of sarcopenic residents compared with nonsarcopenic and presarcopenic residents. METHODS: Sarcopenia assessment was performed among 63 nursing home residents in Baden-Wuerttemberg (D) using the European Working Group on Sarcopenia in Older People 2 specifications. Structured activity sessions (per week), accelerometer-based physical activity (steps/day), and sedentary behavior (percentual/day) were examined. The group comparisons were determined with Kruskal-Wallis tests and Dunn-Bonferroni post hoc tests. RESULTS: Significant differences were found for number of steps (p = 0.005) and percentual sedentary behavior (p = 0.019). Moreover, steps per day presented significant results in group comparison for no sarcopenia (2824.4 [423-14275]) with probable sarcopenia (1703.9 [118-5663]) and confirmed/severe sarcopenia (1571.2 [240-2392]) (both p = 0.022; |r| = 0.34). Sedentary behavior demonstrated significant differences in groups with no sarcopenia (87.9% [69.1-94.3]) and with probable sarcopenia (91.7% [80.4-9835]) (p = 0.018; |r| = 0.35). CONCLUSION: Nonsarcopenic residents demonstrated a higher number of steps and lower sedentary behavior compared with presarcopenic and sarcopenic residents. Increasing steps, reducing sedentary behavior and promoting activities of daily living can contribute to the prevention and treatment of sarcopenia in the nursing home setting.

The relationship between pre-surgery self-rated health and changes in functional and mental health in older adults: insights from a prospective observational study.

BACKGROUND: Elective surgeries are among the most common health stressors in later life and put a significant risk at functional and mental health, making them an important target of research into healthy aging and physical resilience. Large-scale longitudinal research mostly conducted in non-clinical samples provided support of the predictive value of self-rated health (SRH) for both functional and mental health. Thus, SRH may have the potential to predict favorable adaptation processes after significant health stressors, that is, physical resilience. So far, a study examining the interplay between SRH, functional and mental health and their relative importance for health changes in the context of health stressors was missing. The present study aimed at addressing this gap. METHODS: We used prospective data of 1,580 inpatients (794 complete cases) aged 70 years or older of the PAWEL study, collected between October 2017 and May 2019 in Germany. Our analyses were based on SRH, functional health (Barthel Index) and self-reported mental health problems (PHQ-4) before and 12 months after major elective surgery. To examine changes and interrelationships in these health indicators, bivariate latent change score (BLCS) models were applied. RESULTS: Our analyses provided evidence for improvements of SRH, functional and mental health from pre-to-post surgery. BLCS models based on complete cases and the total sample pointed to a complex interplay of SRH, functional health and mental health with bidirectional coupling effects. Better pre-surgery SRH was associated with improvements in functional and mental health, and better pre-surgery functional health and mental health were associated with improvements in SRH from pre-to-post surgery. Effects of pre-surgery SRH on changes in functional health were smaller than those of functional health on changes in SRH. CONCLUSIONS: Meaningful changes of SRH, functional and mental health and their interplay could be depicted for the first time in a clinical setting. Our findings provide preliminary support for SRH as a physical resilience factor being associated with improvements in other health indicators after health stressors. Longitudinal studies with more timepoints are needed to fully understand the predictive value of SRH for multidimensional health. TRIAL REGISTRATION: PAWEL study, German Clinical Trials Register, number DRKS00013311. Registered 10 November 2017 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013311 .

Frailty index and its association with the onset of postoperative delirium in older adults undergoing elective surgery.

BACKGROUND: The association of frailty based on the accumulation of deficits with postoperative delirium (POD) has been poorly examined. We aimed to analyze this association in older patients undergoing elective surgery. METHODS: Preoperative data was used to build a 30-item frailty index (FI) for participants of the PAWEL-study. Delirium was defined by a combination of I-CAM and chart review. Using logistic regressions models we analysed the association between frailty and POD adjusting for age, sex, smoking, alcohol consumption, education and type of surgery. RESULTS: Among 701 participants (mean age 77.1, 52.4% male) median FI was 0.27 (Q1 0.20| Q3 0.34), with 528 (75.3%) frail participants (FI ≥ 0.2). Higher median FI were seen in orthopedic than cardiac surgery patients (0.28 versus 0.23), and in women (0.28 versus 0.25 in men). Frail participants showed a higher POD incidence proportion (25.4% versus 17.9% in non-frail). An increased odds for POD was observed in frail versus non-frail participants (OR 2.14 [95% CI 1.33, 3.44], c-statistic 0.71). A 0.1 increment of FI was associated with OR 1.57 [95% CI 1.30, 1.90] (c-statistic 0.72) for POD. No interaction with sex or type of surgery was detected. Adding timed-up-and-go-test and handgrip strength to the FI did not improve discrimination. CONCLUSION: Our data showed a significant association between frailty defined through a 30-item FI and POD among older adults undergoing elective surgery. Adding functional measures to the FI did not improve discrimination. Hence, our preoperative 30-item FI can help to identify patients with increased odds for POD. TRIAL REGISTRATION: PAWEL and PAWEL-R (sub-) study were registered on the German Clinical Trials Register (number DRKS00013311 and DRKS00012797).

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

OBJECTIVE: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. METHODS: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/ß-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. RESULTS: Among risk and prodromal markers, physical inactivity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical inactivity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with ß-diversity. Subthreshold parkinsonism and physical inactivity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and ß-diversity. Constipation was highest in individuals with the Firmicutes-enriched enterotype, and physical inactivity was most frequent in the Bacteroides-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. INTERPRETATION: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2021;90:E1-E12.

[Telemedicine in mobile geriatric rehabilitation : Results of the VITAAL study]. / Telemedizin in der mobilen geriatrischen Rehabilitation : Ergebnisse der VITAAL-Studie.

BACKGROUND: In order to implement the principle of rehabilitation before care, adaptive concepts for geriatric patients are required. Patients with visual impairments, impaired communication skills, mental illnesses or cognitive deficits are often not or only insufficiently treatable in a rehabilitation clinic. Mobile geriatric rehabilitation (MoGeRe) closes this gap in the care system, but its scope is limited. With the 22 locations in Germany, it is not possible to make a comprehensive MoGeRe possible so far. Telemedicine offers solutions here. OBJECTIVE: Telemedicine supplements to MoGeRe in the form of video visits and video recording were examined with respect to their feasibility and acceptance in a very old target group. METHOD: A total of 101 video visits and 26 diagnostic video recordings were carried out with 25 patients. Interviews with patients and team members were evaluated with the help of a qualitative content analysis. RESULTS AND DISCUSSION: In particular, the acceptance of the video visit was high among all those involved. Its potential lies in the adaptation of the individual treatment, motivation, medical guidance and supervision of the team. The video recording can offer the opportunity to enrich the interdisciplinary exchange and to evaluate and adapt the therapeutic procedure. Specific strategies such as accompanying relatives, explaining the procedure and good timing are necessary for cognitively impaired patients. Our results prove that older people should also be taken into account as users of digital media.

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

OBJECTIVE: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. METHODS: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/ß-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. RESULTS: Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with ß-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and ß-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. INTERPRETATION: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020;88:320-331.

[Nonpharmaceutical concepts for prevention and treatment of delirium]. / Nichtmedikamentöse Konzepte zu Prävention und Behandlung eines Delirs.

BACKGROUND: Cognitive impairment is common among older patients in German hospitals (40%). Dementia, other brain diseases and frailty significantly increase the risk of delirium and pose great challenges to interdisciplinary and interprofessional teams. Delirium prevention is achievable but requires complex interdepartmental strategies with specific components for timely recognition of the individual delirium risk, to carry out structured and sustained implementation of appropriate measures for delirium prevention as well as prompt etiological diagnostics and immediate treatment when delirium occurs. OBJECTIVE: The present work aims to shed light on the role of interprofessional and interdisciplinary collaboration in evidence-based, nonpharmacological delirium prevention programs. MATERIAL AND METHODS: Narrative review of international best practice programs. RESULTS: Nonpharmacological prevention of delirium is effective but requires differentiated risk identification, regular delirium screening and daily targeted cognitive activation and sleep promotion. This can only be achieved in close interprofessional collaboration and is mostly carried out interdepartmentally by specialized teams. DISCUSSION: Interprofessional multicomponent programs for delirium prevention hold the potential to reduce delirium and complication rates in older high-risk patients in regular care, thereby improving treatment and long-term quality of life. Additional interprofessional delirium prevention teams are deployed in different settings simultaneously and provide regular training on optimal delirium management. Demonstration of the effectiveness of cross-setting programs requires large multicenter studies and is therefore particularly laborious.

The effect of age and gender on anti-saccade performance: Results from a large cohort of healthy aging individuals.

By 2050, the global population of people aged 65 years or older will triple. While this is accompanied with an increasing burden of age-associated diseases, it also emphasizes the need to understand the effects of healthy aging on cognitive processes. One such effect is a general slowing of processing speed, which is well documented in many domains. The execution of anti-saccades depends on a well-established brain-wide network ranging from various cortical areas and basal ganglia through the superior colliculus down to the brainstem saccade generators. To clarify the consequences of healthy aging as well as gender on the execution of reflexive and voluntary saccades, we measured a large sample of healthy, non-demented individuals (n = 731, aged 51-84 years) in the anti-saccade task. Age affected various aspects of saccade performance: The number of valid trials decreased with age. Error rate, saccadic reaction times (SRTs), and variability in saccade accuracy increased with age, whereas anti-saccade costs, accuracy, and peak velocity of anti-saccades and direction errors were not affected by age. Gender affected SRTs independent of age and saccade type with male participants having overall shorter SRTs. Our rigid and solid statistical testing using linear mixed-effect models provide evidence for a uniform slowing of processing speed independent of the actually performed eye movement. Our data do not support the assumption of a specific deterioration of frontal lobe functions with aging.

Application of the movement disorder society prodromal Parkinson's disease research criteria in 2 independent prospective cohorts.

BACKGROUND: The research criteria for prodromal PD of the MDS propose a new approach for the assessment of the individual probability of prodromal PD. These criteria require a testing of their reliability in different prospective cohorts. OBJECTIVES: The objective was to evaluate the MDS prodromal PD criteria in 2 independent prospective studies. METHODS: Prodromal PD probabilities of the Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration cohort (TREND study, n = 650, recruited by the presence of probable rapid eye movement sleep behavior disorder, depression, and/or hyposmia or none of these at baseline and 2-, 4-, and 6-year follow-up) and the population-based Prospective Evaluation of Risk Factors for Idiopathic Parkinson's Syndrome cohort (PRIPS Tübingen subsample; n = 715, baseline and 3- and 5-year follow-up) were calculated. Baseline posttest probabilities, time to PD diagnosis, marker constellations, and longitudinal changes of prodromal PD probabilities were analyzed. RESULTS: Incident PD cases (TREND, n = 10; PRIPS = 7) showed significantly higher likelihood ratios of risk and prodromal markers at baseline when compared with nonconverters. Only 2 of 17 incident PD cases met the criteria for probable prodromal PD (ie, posttest probability > 80%) and 5 had possible prodromal PD (ie, > 50%) 1.4 to 3.8 years before diagnosis. The criteria showed high specificity and negative predictive values (>98%), but low sensitivity (TREND, 30%; PRIPS, 14%) and positive predictive values (TREND, 19%, PRIPS, 50%). The individual risk for prodromal PD in incident PD cases showed an inverse correlation with the time to conversion (Spearman rho = .80, P = .006) and unlike in nonconverters, increased during follow-up. CONCLUSION: The MDS prodromal criteria provide a practical framework for the calculation of prodromal PD risk. Although specificity of the criteria is high, most patients will not meet the criteria before diagnosis unless testing is thoroughly performed with numerous and highly specific markers objectively assessed. © 2017 International Parkinson and Movement Disorder Society.

[Diagnostics and multimodal treatment of depression in old age : New developments]. / Diagnostik und multimodale Therapie der Altersdepression : Neue Entwicklungen.

Depressive disorders in elderly persons are frequent and can either first be manifested at a younger age and show a recurrent pattern during later life (ICD 10, F33.*) or have an onset beyond 60 years, which is termed late onset depression (LOD). This LOD has a higher tendency to chronification and implies an increased risk of progression, especially to vascular dementia. The multifactorial genesis of depression in old age includes psychosocial, vascular and metabolic factors and requires multimodal therapy modules at the biological and psychosocial level, which is now increasingly being empirically proven. Depressive disorders with executive and cognitive deficits have to be considered a defined entity with respect to prognosis and treatment. As a first step of treatment watchful waiting is appropriate, especially in depressive adjustment disorders triggered by acute psychosocial stressors (e.g. loss of relatives and conflicts). After 2-4 weeks pharmacological antidepressant therapy should be initiated, at least in a moderate depressive episode. Furthermore, the revised national guidelines for depressive disorders also explicitly recommend psychotherapy as an alternative or supplement to pharmacotherapy in the elderly. Several forms of psychotherapy are emphasized: cognitive behavioral therapy, interpersonal therapy and in particular problem solving, as this is a form of treatment that can also be carried out by other professional groups, thus alleviating the treatment gap caused by the lack of psychotherapists. In summary, a depressive disorder in old age should not induce therapeutic nihilism: after stepped diagnostic assessments, multimodal therapies are individually adapted to the physical, cognitive and social resources of the patients.

[Implementation of auricular acupuncture by the NADA protocol in geriatric patients suffering from major depression : A mixed methods feasibility study]. / Implementierung von Ohrakupunktur nach dem NADA-Protokoll bei geriatrischen Patienten mit einer depressiven Episode : Eine Machbarkeitsstudie mit gemischten Methoden.

BACKGROUND: The number of elderly patients with depression has steadily increased in recent years; therefore, new treatment options and therapy approaches are urgently needed to improve treatment in this patient group. The aim of this project was to evaluate the additional application of auricular acupuncture according to the NADA protocol in patients treated in a daytime ward in terms of acceptability and feasibility. METHODS: A total of 20 psychogeriatric patients from a daytime clinic suffering from major depression (ICD-10: F32-F33) received auricular acupuncture in addition to the standard treatment three times per week over a treatment course of 3 weeks. Semi-structured interviews were conducted with the participants and the therapeutic team and qualitative content analyses were carried out. Depression, cognition, quality of sleep and quality of life were assessed using validated quantitative instruments. RESULTS: There was a 95 % utilization of the therapy. The qualitative analysis showed a high acceptance by all participants. The dominant perception by the patients was a positive expectation and conviction that acupuncture was an effective form of therapy without side effects, which could contribute to recovery. The majority of patients also felt that there was an improvement in the symptoms. The quantitative analysis revealed significant improvements in the target parameters. CONCLUSION: The acceptance of the intervention by the patients and the willingness of the interdisciplinary team underlines the feasibility of this implementation within a fixed therapeutic concept. The significant pre-post improvements indicated a potential benefit and should be verified in further efficacy studies.

The relation of SMI and the VSEP in a risk sample for neurodegenerative disorders.

Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with Alzheimer's disease and subjects with mild cognitive impairment compared to age-matched healthy controls. In this study, the association of VSEP with subjective memory impairment (SMI), a potential risk or prodromal marker for Alzheimer's disease, was examined. The association of VSEP latencies and SMI was studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders. The results show increased VSEP latencies for peak P2 at Fz-F4 in subjects who report SMI and are worried about it as compared to subjects who report memory impairment, but are not concerned and subjects without complaints. The results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer's disease.

Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.

Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 µg/g; n = 602), moderate (> 50-100 µg/g; n = 64) and high (> 100 µg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.

Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers.

With disease-modifying treatment for Parkinson's disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan-Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan-Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.