Impact of depressive symptoms on medication adherence in older adults with chronic neurological diseases.

BACKGROUND: Nonadherence to medication contributes substantially to worse health outcomes. Especially among older adults with chronic illness, multimorbidity leads to complex medication regimes and high nonadherence rates. In previous research, depressive symptomology has been identified as a major contributor to nonadherence, and some authors hypothesize a link via motivational deficits and low self-efficacy. However, the exact mechanisms linking depressive symptomology and nonadherence are not yet understood. This is in part because the often-employed sum scores cannot do justice to the complexity of depressive symptomology; instead, it is recommended to assess the influence of individual symptoms. METHODS: Following this symptom-based approach, we performed correlation, network and regression analysis using depressive symptoms as depicted by the items of the revised Beck Depression Inventory II (BDI) to assess their influence with nonadherence in N = 731 older adults with chronic neurological diseases. Nonadherence was measured with the self-report Stendal Adherence to Medication Score (SAMS). RESULTS: Even when controlling for sociodemographic and health-related covariates, the BDI remained the most influential contributor to nonadherence. Across different methods, Loss of Interest and Difficulty with Concentration were identified as particularly influential for nonadherence, linking nonadherence with other affective or somatic BDI items, respectively. Additionally, Fatigue, Problems with Decision Making, Suicidal Thoughts, and Worthlessness contribute to nonadherence. CONCLUSION: Using a symptom-driven approach, we aimed to understand which depressive symptoms contribute to higher levels of nonadherence. Our results refine previous hypotheses about motivation and control beliefs by suggesting that it is not merely a lack of beliefs in the efficacy of medication that connects depressive symptoms and nonadherence, but rather an overall lack of interest in improving one's health due to feelings of worthlessness and suicidal tendencies. This lack of interest is further substantiated by already sparse resources caused by changes in concentration and fatigue. In order to improve health outcomes and reduce nonadherence, these associations between depressive symptoms must be further understood and targeted in tailored interventions.

An examination of anxiety and its influence on health-related quality of life in Parkinson's disease using the geriatric anxiety scale: a cross-sectional study.

BACKGROUND: Anxiety is one of the most common but often overlooked mood-related nonmotor symptoms in people with Parkinson's disease (PD). To improve the well-being of people with PD, it is important to understand the impact of anxiety in PD, especially its association with depressive and motor symptoms and its impact on health-related quality of life (HRQoL). METHODS: 91 people with PD were assessed between June 2017 and June 2018. Anxiety was measured using the Geriatric Anxiety Scale (GAS) and its cognitive, somatic, and affective subscales. HRQoL was assessed using the Parkinson's Disease Questionnaire 39 (PDQ-39). Moreover, sociodemographic information, depressive symptoms, cognition, motor and nonmotor symptoms were assessed. Descriptive statistics, regression analyses, and path analyses were performed to understand predictors of anxiety and its influence on HRQoL. RESULTS: Of the 91 people with PD, 35 (38.5%) experienced anxiety. Anxiety symptoms in these individuals primarily manifest as somatic sensations. Anxiety, motor, and depressive symptoms are interlinked but contribute individually to HRQoL. Beyond motor symptoms, cognitive and affective aspects of anxiety impact HRQoL. While anxiety and depression overlap, the somatic and cognitive aspects of anxiety play a significant role in determining HRQoL in addition to depressive symptoms. CONCLUSION: Our study used the GAS and its three subscales to shed light on the connections between anxiety, depression, and motor impairment in people with PD. Although anxiety is linked to depression and motor symptoms, it independently affects the HRQoL of people with PD. Thus, it is crucial to adopt a comprehensive diagnostic approach that detects and considers the impact of anxiety on HRQoL in PD.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.

Self-management of geriatric syndromes - an observational study.

BACKGROUND: Self-management of health refers to various actions and decisions that impact health outcomes. To improve health, independence, and quality of life (QoL) while reducing healthcare utilization and costs, patients' self-management abilities can be enhanced. However, disease-specific self-management interventions may not be applicable for older adults with multiple illnesses. Instead, focusing on prevalent geriatric syndromes, such as frailty, cognitive decline, pain, incontinence, or impaired mobility, may be more beneficial. To achieve this, a detailed understanding of the specific needs of the older population is crucial. METHODS: Patients who are 70 years old or older will be chosen from four geriatric hospitals, which include both inpatient and outpatient facilities. At baseline, each participant will undergo a comprehensive geriatric evaluation and answer various questionnaires that focus on their current self-management abilities, self-efficacy, anxiety, aging perception, and QoL. Moreover, extensive data on the presence and impact of geriatric syndromes will be gathered. Three and six months after the initial evaluation, follow-up assessments will be conducted to identify any changes in participants' health, independence in daily activities, geriatric syndromes, cognition and mood, QoL, and self-management. DISCUSSION: The present investigation aims to assess the factors that may facilitate or impede self-management in older adults afflicted with geriatric syndromes. Instead of concentrating on particular diseases, this study will analyze the association between self-management and geriatric syndromes. The information obtained will contribute to clinical expertise on the self-management habits of older adults and their effects on their well-being, autonomy, and overall QoL, as well as provide insights into geriatric syndromes. This valuable knowledge will be crucial for developing personalised programs to enhance self-management among older adults. TRIAL REGISTRATION: German Trial Register (Deutsches Register Klinischer Studien) DRKS00031016.

Gait Characteristics Associated with Fear of Falling in Hospitalized People with Parkinson's Disease.

BACKGROUND: Fear of falling (FOF) is common in Parkinson's disease (PD) and associated with distinct gait changes. Here, we aimed to answer, how quantitative gait assessment can improve our understanding of FOF-related gait in hospitalized geriatric patients with PD. METHODS: In this cross-sectional study of 79 patients with advanced PD, FOF was assessed with the Falls Efficacy Scale International (FES-I), and spatiotemporal gait parameters were recorded with a mobile gait analysis system with inertial measurement units at each foot while normal walking. In addition, demographic parameters, disease-specific motor (MDS-revised version of the Unified Parkinson's Disease Rating Scale, Hoehn & Yahr), and non-motor (Non-motor Symptoms Questionnaire, Montreal Cognitive Assessment) scores were assessed. RESULTS: According to the FES-I, 22.5% reported low, 28.7% moderate, and 47.5% high concerns about falling. Most concerns were reported when walking on a slippery surface, on an uneven surface, or up or down a slope. In the final regression model, previous falls, more depressive symptoms, use of walking aids, presence of freezing of gait, and lower walking speed explained 42% of the FES-I variance. CONCLUSION: Our study suggests that FOF is closely related to gait changes in hospitalized PD patients. Therefore, FOF needs special attention in the rehabilitation of these patients, and targeting distinct gait parameters under varying walking conditions might be a promising part of a multimodal treatment program in PD patients with FOF. The effect of these targeted interventions should be investigated in future trials.

The impact of poor medication knowledge on health-related quality of life in people with Parkinson's disease: a mediation analysis.

PURPOSE: This study aimed to determine how limited medication knowledge as one aspect of health literacy contributes to poorer health-related quality of life (HRQoL) in people with Parkinson's disease (PD). METHODS: Demographical data, PD-specific data (MDS-Unified Parkinson's Disease-Rating Scale, Nonmotor symptom scale), and data about depressive symptoms (Beck's depression inventory), cognition (Montreal cognitive assessment), HRQoL (Short-Form Health Questionnaire-36, SF-36), and medication knowledge (names, time of taking, indication, dosage) were assessed in 193 patients with PD. Multivariate analysis of variance (MANOVA), multivariate analysis of covariance, and mediation analyses were used to study the relationship between medication knowledge and HRQoL in combination with different mediators and covariates. RESULTS: Overall, 43.5% patients showed deficits in at least one of the 4 knowledge items, which was associated with higher age, number of medications per day and depression level, and poorer cognitive function, motor function, and lower education level. Using one-way MANOVA, we identified that medication knowledge significantly impacts physical functioning, social functioning, role limitations due to physical problems, and role limitations due to emotional problems. Mediation models using age, education level, and gender as covariates showed that the relationship between knowledge and SF-36 domains was fully mediated by Beck's Depression Inventory but not by Montreal Cognitive Assessment. CONCLUSIONS: Patients who expressed unawareness of their medication did not necessarily have cognitive deficits; however, depressive symptoms may instead be present. This concomitant depressive symptomatology is crucial in explaining the contribution of nonadherence and decreased medication knowledge to poor quality of life.

Fear of Falling Does Not Influence Dual-Task Gait Costs in People with Parkinson's Disease: A Cross-Sectional Study.

Cognitive deficits and fear of falling (FOF) can both influence gait patterns in Parkinson's disease (PD). While cognitive deficits contribute to gait changes under dual-task (DT) conditions, it is unclear if FOF also influences changes to gait while performing a cognitive task. Here, we aimed to explore the association between FOF and DT costs in PD, we additionally describe associations between FOF, cognition, and gait parameters under single-task and DT. In 40 PD patients, motor symptoms (MDS-revised version of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr), FOF (Falls Efficacy Scale International), and Montreal Cognitive Assessment (MoCA) were assessed. Spatiotemporal gait parameters were recorded with a validated mobile gait analysis system with inertial measurement units at each foot while patients walked in a 50 m hallway at their preferred speed under single-task and DT conditions. Under single-task conditions, stride length (ß = 0.798) and spatial variability (ß = 0.202) were associated with FOF (adjusted R2 = 0.19, p < 0.001) while the MoCA was only weakly associated with temporal variability (adjusted R2 = 0.05, p < 0.001). Under DT conditions, speed, stride length, and cadence decreased, while spatial variability, temporal variability, and stride duration increased with the largest effect size for speed. DT costs of stride length (ß = 0.42) and age (ß = 0.58) explained 18% of the MoCA variance. However, FOF was not associated with the DT costs of gait parameters. Gait difficulties in PD may exacerbate when cognitive tasks are added during walking. However, FOF does not appear to have a relevant effect on dual-task costs of gait.

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model.

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean- (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model-derived parameters. Case-control comparisons revealed widespread ALS-related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel-wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.

Impact of subthreshold depression on health-related quality of life in patients with Parkinson's disease based on cognitive status.

BACKGROUND: In patients with Parkinson's disease (PD), depression has a strong impact on quality of life (QoL). However, little is known about the influence of subthreshold depression (STD) on QoL in PD patients. METHODS: A total of 230 hospitalized PD patients with normal and impaired cognitive status were included in this observational study. We collected the following data for analysis: Beck Depression Inventory level, Montreal Cognitive Assessment (MOCA) score, non-motor symptoms questionnaire score, PD questionnaire-39 (PDQ-39) score, Hoehn-Yahr stage, and Movement Disorder Society-sponsored revision of the unified PD rating scale III (MDS-UPDRS III) score. To study the impact of STD on the PDQ-39 summary index (SI) and its domains, we used multivariate analysis of variance and multivariate analysis of covariance. RESULTS: In this cohort, 80 (34.8%) patients had STD [44 (32.3%) with high MOCA score (> 21) and 36 (38.3%) with low MOCA score (< 21)]. In PDQ-39 SI, there was a significant effect on depression level. In patients with higher MOCA score, STD was associated with worse PDQ-39 domains emotional well-being and cognition, whereas in patients with lower MOCA score, STD had no significant effect on PDQ-39 SI or its subdomains. CONCLUSION: In PD patients, QoL is significantly affected by STD, and thus, more attention in medical care should be focused on treating STD. However, the impact is only observable in PD patients with normal cognitive function. STD patients show more reduced QoL than non-depressed patients, indicating that STD should be treated as a transition zone between normal mood and depression.

Expectations and behaviour of older adults with neurological disorders regarding general practitioner consultations: an observational study.

BACKGROUND: Patients' relationship with their GPs is linked to adherence, patient behaviour and satisfaction with healthcare. Several factors pertaining to this relationship have already been identified, however expectations and preferences vary depending on age and diagnosis. Chronically ill elderly patients constitute a group of patients with specific needs that are not yet understood. METHODS: For this observational study, 100 (44 female, mean age 72.72 + - 8.28 years) patients were interviewed. Multiple linear or binary logistic regression as well as analysis of variance was used to understand the link between factors pertaining to GP relationship and patient behaviour, and principal component analysis was performed to understand the underlying structure of patients' needs. RESULTS: Patients attribute high importance to their GP's opinion of them. On average, what the GP thinks about the patients is almost as important as what their partners think. Patients primarily want to be perceived as engaged, friendly and respected individuals, and it is important for patients to be liked by their GP. This importance is linked to active preparation; 65% of the patients prepared actively for GP consultations. Expectations regarding GP consultations can be split into two components: a medical aspect with a subfactor concerning emotional support, and a social component. Prominent factors influencing the relationship are the possibility to talk about emotions and mental well-being, trust, and GP competency. Satisfaction and trust were mainly linked to medical competency. Being able to show emotions or talk about mental well-being enhances perceived GP competence, satisfaction, and active patient preparation. However, a focus on the social component such as frequent talking about private topics reduces both perceived GP competency as well as active patient preparation. CONCLUSION: Older patients take GP consultations seriously, and their expectations regarding GP consultations focus on medical competence and care as well as empathetic listening and understanding. Older persons seek a deeper connection to their GPs and are willing to be active and cooperative. As the patient-GP relationship influences health outcomes, treatment of older patients should be adjusted to enable this active participation.

Modelling disease course in amyotrophic lateral Sclerosis: pseudo-longitudinal insights from cross-sectional health-related quality of life data.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with limited robust disease-modifying therapies presently available. While several treatments are aimed at improving health-related quality of life (HRQoL), longitudinal data on how QoL changes across the disease course are rare. OBJECTIVES: To explore longitudinal changes in emotional well-being and HRQoL in ALS. METHODS: Of the 161 subjects initially recruited, 39 received 2 subsequent follow-up assessments at 6 and 12 months after baseline. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess physical impairment. HRQoL was assessed using the ALS Assessment Questionnaire (ALSAQ-40). The D50 disease progression model was applied to explore longitudinal changes in HRQoL. RESULTS: Patients were primarily in the early semi-stable and early progressive model-derived disease phases. Non-linear correlation analyses showed that the ALSAQ-40 summary index and emotional well-being subdomain behaved differently across disease phases, indicating that the response shift occurs early in disease. Both the ALSFRS-R and ALSAQ-40 significantly declined at 6- and 12-monthly follow-ups. CONCLUSION: ALSAQ-40 summary index and emotional well-being change comparably over both actual time and model-derived phases, indicating that the D50 model enables pseudo-longitudinal interpretations of cross-sectional data in ALS.

Cognitive deficits have only limited influence on health-related quality of life in amyotrophic lateral sclerosis.

OBJECTIVE: To explore the association between cognitive deficits and health-related quality of life in amyotrophic lateral sclerosis (ALS). METHODS: The revised ALS Functional Rating Scale (ALSFRS-R for physical impairment), the ALS Assessment Questionnaire (ALSAQ-40 for health-related quality of life) and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS for cognition) were assessed in 125 patients with ALS. Correlations between ALSAQ-40 domains and ECAS functions were tested using Spearman correlation. Linear regression was used to evaluate the relationship between dysphagia, depression, hopelessness, pain (all derived from corresponding items from the ALSFRS-R or ALSAQ-40), ALSFRS-R, ECAS and the ALSAQ-40. RESULTS: Verbal fluency, language and executive function were disturbed in 69 (55%), 54 (43%) and 41 (33%) patients, respectively. In the ALS non-specific domains the memory and visuospatial function were impaired in 44 (35%) and 12 (10%) patients. In the non-demented group the five ECAS functions did not correlate with the ALSAQ-40 subdomains. The ALSFRS-R score, hopelessness, pain, and depression explained 65% of the ALSAQ-40 SI variance; the ECAS total score did not significantly predict ALSAQ-40 summary index. The ECAS visuospatial, executive function and fluency significantly predicted emotional well-being (adjusted R2 = 0.08). When the model was controlled for depression, hopelessness and pain none of the ECAS functions (visuospatial, executive function and fluency) were significant predictors of emotional well-being. CONCLUSION: Deficits in visuospatial function, executive function and fluency constrain the ability to manage activities of daily living and this might cause decline in well-being.

Measuring Anxiety in Older Adults: Development, Diagnostic Accuracy, and Preliminary Validation of a Short-Form of the German Geriatric Anxiety Scale (GAS-G-SF).

Anxiety symptoms and anxiety disorders are highly prevalent among older adults, and are associated with considerable distress, functional impairment, and burden. Also, there is growing need for brief instruments to measure anxiety symptoms in primary care and geriatric medical settings. Therefore, the current study focuses on the development and psychometric evaluation of a short-form of the Geriatric Anxiety Scale (GAS-G), a well-established anxiety instrument for use with older adults. Study 1 draws on the original data from the GAS-G validation study (N = 242) to develop the short-form (GAS-G-SF) and determines whether the results replicate with the short-form. Study 2 extends the validation of the GAS-G-SF to a clinical sample (N = 156; 62 patients with heart disease, 94 patients with Parkinson's disease). Overall, the GAS-G-SF showed promising psychometric properties in terms of internal consistency and validity. Also, the GAS-G-SF showed good discriminatory power based on receiver operating characteristic curve analysis in both studies. These results support the utility of the GAS-G-SF as a brief assessment measure for anxiety.

[Parkinson Networks in Germany: Future or Utopia?] / Parkinson-Netzwerke in Deutschland: Zukunft oder Utopie?

BACKGROUND: Parkinson's disease requires a close interaction between different care partners from the point of diagnosis in order to provide the best possible care for patients. However, the treatment reality shows that there are often still significant gaps in care. In recent years it has been recognised that the formation of networks can contribute to improving the care of Parkinson's patients. OBJECTIVES: To present the current status of the development of Parkinson's networks in Germany, the available evidence and the future of Parkinson's networks. MATERIAL AND METHODS: Experiences from existing networks in Germany were systematically recorded on the basis of personal reports and publications. The existing national and international evidence was summarised, and critical success factors and hurdles were analysed. In addition, possible future scenarios were developed. RESULTS: There are many integrated approaches to improve the care of Parkinson's patients. However, this is usually subject to the initiative at individual locations, without binding conditions being created for this by the legislator or the funding agencies outside of model projects. DISCUSSION: It must be noted that it is currently very difficult to implement a problem-free and cost-efficient development of intersectoral network structures within the existing possibilities of the German health care system. The high personal commitment of individual actors currently forms the basis of existing regional networks. An overarching health policy concept is needed to further promote the content and infrastructure of Parkinson's disease networks.

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

Interferon-γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A mice.

Motor neurons are markedly vulnerable to excitotoxicity mostly by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) stimulation and are principal targets in the neurodegenerative disease Amyotrophic Lateral Sclerosis. Interferon-gamma (IFN-γ), a pro-inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium-permeable complex of IFN-γ receptor 1(IFNGR1) subunit and AMPAR subunit GluR1. This receptor complex is formed via a non-canonical neuron-specific IFN-γ pathway that involves Jak1/Stat1 and Protein Kinase A. In this study, we explore the expression of the pathway's participants for the first time in the hSOD1G93A Amyotrophic Lateral Sclerosis mouse model. Elevated IFNGR1 and GluR1 are detected in motor neurons of hSOD1G93A symptomatic mice ex vivo, unlike the downstream targets - Jak1, Stat1, and Protein Kinase A. We, also, determine effects of IFN-γ alone or in the presence of an excitotoxic agent, kainate, on motor neuron survival in vitro. IFN-γ induces neuronal damage, but does not influence kainate-mediated excitotoxicity. Increased IFNGR1 can most likely sensitize motor neurons to excitotoxic insults involving GluR1 and/or pathways mediated by IFN-γ, thus, serving as a potential direct link between neurodegeneration and inflammation in Amyotrophic Lateral Sclerosis.

Plasma VCAM1 levels correlate with disease severity in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development of novel neuroprotective therapies. OBJECTIVE: Assessing potential dysregulation of a panel of inflammatory mediators in the peripheral blood mononuclear cells (PBMCs) and plasma of PD patients and in the context of clinical outcome metrics. METHODS: We performed a screening of selected cell-surface chemokine receptors and adhesion molecules in PBMCs from PD patients and age-matched healthy controls in a flow cytometry-based assay. ELISA was used to quantify VCAM1 levels in the plasma of PD patients. Lymphocytic chemotactic ability was assessed using a modified Boyden chamber assay. RESULTS: VLA4 expression was significantly downregulated on CD3+ T cells, CD56+ NK cells, and CD3+/CD56+ NK-T cells from PD patients; further, an increase of the soluble VLA4 ligand VCAM1 in patient plasma was noted. sVCAM1 in PD patients was even higher than reported for patients with multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis. sVCAM1 levels correlated with the disease stage (Hoehn and Yahr scale) and motor impairment. Chemoattraction with SDF-1α revealed impaired motility of lymphocytes from PD patients relative to controls. CONCLUSION: Our data provides evidence for a functional dysregulation of the sVCAM1-VLA4 axis in PD. Further studies evaluating the therapeutic potential of this axis are warranted.

Cerebral patterns of neuropsychological disturbances in hepatitis C patients.

Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.

Adherence to medication in neurogeriatric patients: an observational cross-sectional study.

BACKGROUND: Poor adherence is a major issue and is associated with increased morbidity, mortality, and immense costs for the healthcare system. Due to demographic changes, the burden of neurological diseases is increasing with a crucial exacerbation of the problem of nonadherence. However, comprehensive data on geriatric patients with neurological disorders do not exist to date. In this cross-sectional observational study we aim to identify disease-specific adherence-modulating factors in neurogeriatric patients. METHODS: Patients 60 years or older with neurological disorders will receive an assessment of adherence (Stendal Adherence with Medication Score) and a comprehensive geriatric assessment during their stay in the Department of Neurology or Geriatrics at the Jena University Hospital (baseline data). In addition disease specific data will be derived from medical records. After one and twelve months a telephone interview will be conducted to evaluate if and why changes of medication occurred (follow up data). DISCUSSION: This study aims to explore disease-specific patterns of nonadherence in elderly patients with neurological disorders and characteristics of information transfer between a specialized center, practicing neurologists, general practitioners, and the patients and their caregivers. This comprehensive data may help to develop and apply complex and disease-specific interventions to enhance adherence. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016774. Registered 19.02.2019.

Dysphagia from a neurogeriatric point of view : Pathogenesis, diagnosis and management.

Dysphagia is becoming increasingly more common in aging societies and, like the classical geriatric syndromes, it is a relevant functional impairment. The prevalence of dysphagia is highest in the group of old patients with neurological disorders, particularly in patients with stroke, dementia and Parkinson's disease. In the various neurological diseases of older people disease-specific factors often have a decisive influence on the clinical management of dysphagia. In addition, the concept of primary and secondary presbyphagia plays an important role in understanding age-related dysphagia. Whereas at the organ level of the International Classification of Functioning, Disability and Health (ICF) model, the diagnosis and treatment of dysphagia in neurogeriatrics have already made progress, more research is needed on the levels of activity/mobility, social environment, personal factors and the environment. This article summarizes the pathophysiological aspects as well as the current evidence for diagnosis and treatment of neurogeriatric dysphagia. Due to its high clinical relevance dysphagia should be added to the geriatric syndromes as "impaired swallowing".