RESUMEN
BACKGROUND: C9orf72 repeat expansions have been observed in a wide variety of neurodegenerative disorders. The cut-off between normal and pathogenic alleles is not well established as repeat sizing methods are often semi-quantitative. However, intermediate alleles might influence disease prevalence and phenotype, as seen for other repeat expansion disorders. We aimed to further delineate the prevalence of small, intermediate and expanded C9orf72 alleles and elucidate their potential influence on the disease phenotype. METHODS: DNA derived from patients (n = 1804) and healthy individuals (n = 643) was obtained from multiple collectives in Austria. Genotyping was performed using a two-step PCR assay followed by Southern blotting. RESULTS: 3.4% of clinically diagnosed frontotemporal dementia (FTD; n = 5/147) cases and 0.8% of clinically diagnosed Alzheimer's disease (AD; n = 5/602) cases were carriers of a pathological C9orf72 repeat expansion. A significantly earlier disease onset was detected in expansion carriers compared to non-carriers in the FTD and AD cohorts (median 50 years, range 39-64 vs. median 64 years, range 36-92, p = 0.018 and median 63 years, range 54-71 vs. median 74 years, range 45-92, p = 0.006, respectively). C9orf72 intermediate alleles were significantly associated with cerebellar symptoms (p = 0.0004) and sensory deficits in the dementia cohort (p = 0.01). CONCLUSIONS: C9orf72 repeat expansion carriers showed earlier disease onset compared to non-carriers with clinical diagnosis of FTD and AD. Furthermore, C9orf72 intermediate repeats might modify the phenotypic expression in dementia.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Humanos , Expansión de las Repeticiones de ADN/genética , Proteína C9orf72/genética , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Proteínas/genética , Fenotipo , Esclerosis Amiotrófica Lateral/genéticaRESUMEN
Language impairments, hallmarks of speech/language variant progressive supranuclear palsy, also occur in Richardson's syndrome (PSP-RS). Impaired communication may interfere with daily activities. Therefore, assessment of language functions is crucial. It is uncertain whether the Aachen Aphasia Test (AAT) is practicable in PSP-RS, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's dementia (AD) and language deficits differ in these disorders. 28 PSP-RS, 24 AD, and 24 bvFTD patients were investigated using the AAT and the CERAD-Plus battery. 16-25% of all patients failed in AAT subtests for various reasons. The AAT syndrome algorithm diagnosed amnestic aphasia in 5 (23%) PSP-RS, 7 (36%) bvFTD and 6 (30%) AD patients, Broca aphasia in 1 PSP-RS and 1 bvFTD patient, Wernicke aphasia in 1 bvFTD and 3 (15%) AD patients. However, aphasic symptoms resembled non-fluent primary progressive aphasia in 14 PSP-RS patients. In up to 46% of PSP-RS patients, 61% of bvFTD and 64% of AD patients significant impairments were found in the AAT subtests spontaneous speech, written language, naming, language repetition, language comprehension and the Token subtest. The CERAD-Plus subtest semantic fluency revealed significant impairment in 81% of PSP-RS, 61% of bvFTD, 44% of AD patients, the phonemic fluency subtest in 31, 40 and 31%, respectively. In contrast to bvFTD and AD, severity of language impairment did not correlate with cognitive decline in PSP-RS. In summary, the patterns of aphasia differ between the diagnoses. Local frontal language networks might be impaired in PSP-RS, whereas in AD and bvFTD, more widespread neuropathology might underly language impairment.
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Enfermedad de Alzheimer , Afasia , Demencia Frontotemporal , Trastornos del Desarrollo del Lenguaje , Parálisis Supranuclear Progresiva , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Afasia/etiología , Demencia Frontotemporal/complicaciones , Humanos , Pruebas Neuropsicológicas , Parálisis Supranuclear Progresiva/complicaciones , Parálisis Supranuclear Progresiva/diagnósticoRESUMEN
Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer's disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/diagnóstico por imagen , Austria/epidemiología , Estudios Transversales , Humanos , Estudios Prospectivos , Sistema de RegistrosRESUMEN
Studies on caregiver burden in patients with frontotemporal lobar degeneration are rare, differ methodologically and show variable results. Single center longitudinal pilot study on caregiver burden and potential risk factors in patients with behavioural variant frontotemporal dementia (bvFTD) and semantic (svPPA) and non-fluent variants (nfvPPA) primary progressive aphasia. Forty-six bvFTD, nine svPPA, and six nfvPPA patients and caring relatives were analysed for up to 2 years using the Mini-Mental State Examination as global measure for cognitive performance, Frontal Assessment Battery (frontal lobe functions), Frontal Behavioural Inventory (personality and behaviour), Neuropsychiatric Inventory (dementia-related neuropsychiatric symptoms), Barthel Index and Lawton IADL Scale (basic and instrumental activities of daily living), the Caregiver Strain Index (CSI), and in most participants also the Zarit Burden Interview (ZBI). CSI baseline sum scores were highest in bvFTD (mean ± SD 5.5 ± 3.4, median 5, IQR 6), intermediate in svPPA (2.9 ± 2.3; 3; 3.5) and low in nfvPPA (1.6 ± 2.1; 1; 2). Similar differences of caregiver burden were found using the ZBI. During follow-up, CSI and ZBI sum scores deteriorated in svPPA, not in bvFTD and nfvPPA, and correlated significantly with personality and behaviour, neuropsychiatric symptoms, caregiver age, and instrumental, but not basic activities of daily living, Mini-Mental State Examination scores or frontal lobe functions. This study reveals differences in caregiver burden in variants of frontotemporal lobar degeneration. Caregivers should be systematically asked for caregiver burden from the time of the diagnosis to provide comprehensive support in time.
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Afasia Progresiva Primaria , Demencia Frontotemporal , Actividades Cotidianas , Carga del Cuidador , Humanos , Proyectos Piloto , SemánticaRESUMEN
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) progress relentlessly and lead to a need for care. Caregiving is often burdensome. Little is known about the course of caregiver burden (CB) in PSP and CBS patients. Longitudinal analysis of CB in family members caring for PSP and CBS patients. Single-center longitudinal pilot study in 68 newly diagnosed patients with probable PSP and CBS (52 Richardson's syndrome; 1 progressive gait freezing of PSP; 15 CBS). Demographic, educational, occupational parameters, family status, motor functions (UPDRSIII, Hoehn and Yahr Score, Tinetti) and neuropsychological performance (CERAD Plus, Frontal Assessment Battery) were assessed, as well as behavioral and neuropsychiatric impairments (Frontal Behavioral Inventory, Neuropsychiatric Inventory), activities of daily living (ADL) and caregiver burden using the Caregiver Strain Index (CSI), in most patients also the Zarit Burden Interview (ZBI). Patients were followed up every 6 months for up to 2 years. Caregivers reported mild to moderate CB at baseline, which increased by 25-30% in 2 years and was significantly greater in PSP than in CBS. Risk for mental health problems increased over time, especially in female caregivers (depression). Important patient-related factors were apathy, aspontaneity, depression, irritability, disorganization, poor judgment, impairment of language, impairments in ADL, a high educational level of the patient and close family relationship. Behavioral symptoms and impaired ADL are the main patient-related factors of CB in PSP and CBS. CB can be severe and needs to be assessed repeatedly from the time of diagnosis to provide comprehensive support.
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Parálisis Supranuclear Progresiva , Actividades Cotidianas , Cuidadores , Femenino , Humanos , Proyectos Piloto , SíndromeRESUMEN
INTRODUCTION: Aphasic and other language disturbances occur in patients with epilepsy during and after epileptic seizures. Moreover, the interictal language profile in these patients is heterogeneous, varying from normal language profile to impairment in different language functions. The aim of this paper was to critically review the terms and concepts of ictal language alterations. MATERIAL AND METHOD: For this review we performed an extensive literature search on the term "epileptic aphasia" and analyzed the semiology and terminology indicating language-associated seizure symptoms. In addition, we give an overview on EEG, etiology, and brain imaging findings and ictal language disorders. RESULTS: In the literature, a plethora of terms indicates language-associated seizure symptoms. Simultaneous Video-EEG monitoring represents the gold standard to correctly classify ictal versus postictal language disturbances and to differentiate aphasic symptoms from speech automatisms. Different rhythmic and periodic EEG patterns associated with ictal language disturbances are recognized. Cerebral magnetic resonance imaging (cMRI) is essential in the diagnosis of seizures and epilepsy. Brain tumors and acute or remote cerebrovascular lesions are the most frequently reported structural etiologies underlying ictal language alterations. However, it has to be recognized that brain imaging may show alterations being the consequence of seizures itself rather than its cause. Functional brain imaging might be informative in patients with inconclusive EEG and MRI findings. Overall, seizure-associated aphasia is reported to have good lateralizing significance. CONCLUSION: Various language disturbances are caused by different types of seizures, epilepsies and underlying etiologies. In the clinical context, simultaneous Video-EEG monitoring facilitates precise classification of ictal versus postictal language alterations and differentiation of aphasic symptoms from speech automatisms.
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Afasia , Epilepsia , Afasia/etiología , Encéfalo/diagnóstico por imagen , Electroencefalografía , Epilepsia/complicaciones , Humanos , ConvulsionesRESUMEN
BACKGROUND: Pupil examination represents a diagnostic and prognostic test in the management of several neurological diseases. Infrared video pupillometry (IVP) is the gold standard, since it is not routinely available, a noninvasive bedside ultrasound assessment has been proposed as an alternative. The aim of this study was to assess the feasibility and reproducibility of ultrasound pupillometry (UP) in comparison with IVP. MATERIALS AND METHODS: 81 subjects (43 men and 38 women, mean age: 52â±â20 years and 49â±â19 years, respectively) with no history of neurophthalmologic disease were enrolled. UP was performed with a 12-MHz linear probe according to current guidelines for orbital insonation. Light and painful stimuli were applied to test pupillary light reflex (PLR) and ciliospinal reflex (CR). In 30 of these subjects IVP examination was performed additionally to obtain intra-observer and inter-observer agreement. RESULTS: Increasing age was associated with a decreased pupillary diameter (PD) at rest, after PLR and CR (R -0.728, pâ<â0.01, R -0.643, pâ<â0.01, R 0.674, pâ<â0.001 respectively), while no association was noticed with time to constriction/dilation. UP measurements were reproducible (rate of inter- and intra-observer agreement: R 0.979, pâ<â0.01, R 0.946, pâ<â0.01 respectively) and concordant with IVP (PLR R 0.831, pâ<â0.01; CR R 0.879, pâ<â0.01). CONCLUSION: According to our study, ultrasound pupillometry is a feasible and reliable technique for bedside pupillary function assessment, and is a good alternative to infrared video pupillometry. Moreover, it represents the only way for functional pupillary assessment in patients with periorbital hematoma.
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Pupila , Reflejo Pupilar , Ultrasonografía , Adulto , Anciano , Femenino , Humanos , Luz , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
A substantial number of neurological diseases lead to chronic impairment of activities of daily living (ADL) and physical or mental dependence. In Austria, homecare is provided mostly by female family members. Moreover, mainly female personnel, in the majority from southern and eastern European countries, contributes to care. Dependence and need for care vary between neurological diagnoses and accompanying diseases. Caregiver burden (CB) depends on patient- and caregiver-related and external factors, such as integrity of a family network, spatial resources, and socioeconomic factors. Depending on the neurological diagnosis, disease severity, and behavioral impairment and psychiatric symptoms, caregivers (CG) are at a significant risk of mental and somatic health problems because of limitations in personal needs, occupational and social obligations, financial burden, and restricted family life and leisure. Subjective and objective CB needs to be assessed in time and support should be provided on an individual basis. Recently, COVID-19 has caused additional multifactorial distress to dependent patients and informal and professional CG.
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COVID-19 , Servicios de Atención de Salud a Domicilio , Actividades Cotidianas , Cuidadores , Costo de Enfermedad , Femenino , Humanos , SARS-CoV-2RESUMEN
Trust is one of the foundations of human society and pervades all aspects of human live. Research on humans focused primarily on identifying the biological basis of trust behavior in healthy subjects, and this evidence hints to certain brain areas, hormones, and genetic factors to be fundamentally involved. The contribution of cortisol in trust has not yet elicited much attention in research, especially when specifically examined at basal cortisol levels. Trust has been previously studied in some neurological diseases but not in patients with epilepsy, and the influence of hormones on trust in these diseases remains yet unknown. Against this background, we designed an experimental study with a group of patients with juvenile myoclonic epilepsy and a group of healthy controls to compare trust behavior and plasma cortisol levels between the two groups. This economic game is frequently used in research to operationalize trust behavior. All participants further underwent neuropsychological assessment. Our results showed that there was no significant difference in trust behavior during the trust game, but a trend toward lower trust in patients. Furthermore, there was a significant difference in cortisol levels between groups with lower levels in patients. Interestingly, cortisol levels correlated with trust only in the patient group, but not in the control group. Future studies should specifically differentiate the effect of induced cortisol increases (e.g., acute stress) versus the effect of basal cortisol levels reflecting homeostasis or chronic stress on trust behavior and leverage the potential of comparison between patients and healthy controls.
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Hidrocortisona/sangre , Epilepsia Mioclónica Juvenil/sangre , Epilepsia Mioclónica Juvenil/psicología , Pruebas Neuropsicológicas , Confianza/psicología , Adolescente , Adulto , Biomarcadores/sangre , Femenino , Voluntarios Sanos , Humanos , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Parkinson patients suffering from disease progression become increasingly dependent on personal care, which is mostly provided by female family members. Burden of care correlates with severity of motor impairment, neurocognitive and neuropsychiatric symptoms, behavioral abnormalities, autonomic nervous system disorders, impairment of micturition, sleep, and dependence. Caregiver burden also results from restrictions in time for personal matters, family, leisure and social activities, occupational limits, costs, lack of social support and impairment of sleep, depression, and emotional and other health problems of the carer (such as depression and anxiety). Caregivers at risk of caregiver burden need to be identified in time in order to provide information and adequate personal, psychological and financial support.
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Cuidadores/psicología , Enfermedad de Parkinson , Adaptación Psicológica , Costo de Enfermedad , Depresión , Humanos , Apoyo SocialRESUMEN
There is consensus that the neuropathological characteristic of Parkinson's disease (PD) is the neuronal cell loss of the substantia nigra pars compacta (SNc) in connection with a Lewy pathology. The transsynaptic spread of Lewy pathology is considered essential in PD pathogenesis. Therefore, the knowledge of pre-existing neuroanatomical connections of the SNc is essential. We describe recent animal experiments on the afferent and efferent projections of the SNc and discuss the evidence for and against the sequential transsynaptic spread of Lewy pathology in the pathogenesis of PD.
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Enfermedad de Parkinson , Porción Compacta de la Sustancia Negra , Animales , Humanos , Enfermedad de Parkinson/patología , Porción Compacta de la Sustancia Negra/patologíaRESUMEN
The objective of this work was to develop and evaluate a classifier for differentiating probable Alzheimer's disease (AD) from Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) and from frontotemporal dementia, behavioral variant (bvFTD) based on quantitative electroencephalography (QEEG). We compared 25 QEEG features in 61 dementia patients (20 patients with probable AD, 20 patients with PDD or probable DLB (DLBPD), and 21 patients with bvFTD). Support vector machine classifiers were trained to distinguish among the three groups. Out of the 25 features, 23 turned out to be significantly different between AD and DLBPD, 17 for AD versus bvFTD, and 12 for bvFTD versus DLBPD. Using leave-one-out cross validation, the classification achieved an accuracy, sensitivity, and specificity of 100% using only the QEEG features Granger causality and the ratio of theta and beta1 band powers. These results indicate that classifiers trained with selected QEEG features can provide a valuable input in distinguishing among AD, DLB or PDD, and bvFTD patients. In this study with 61 patients, no misclassifications occurred. Therefore, further studies should investigate the potential of this method to be applied not only on group level but also in diagnostic support for individual subjects.
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Enfermedad de Alzheimer/diagnóstico , Electroencefalografía , Demencia Frontotemporal/diagnóstico , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad de Parkinson/diagnóstico , Anciano , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Diagnóstico Diferencial , Femenino , Demencia Frontotemporal/clasificación , Demencia Frontotemporal/fisiopatología , Humanos , Enfermedad por Cuerpos de Lewy/clasificación , Enfermedad por Cuerpos de Lewy/fisiopatología , Estudios Longitudinales , Masculino , Escala del Estado Mental , Pruebas Neuropsicológicas , Enfermedad de Parkinson/clasificación , Enfermedad de Parkinson/fisiopatología , Estudios Prospectivos , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador , Máquina de Vectores de SoporteRESUMEN
We analyzed the relation of several synchrony markers in the electroencephalogram (EEG) and Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores. The study sample consisted of 79 subjects diagnosed with probable AD. All subjects were participants in the PRODEM-Austria study. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. We employed quadratic least squares regression to describe the relation between MMSE and the EEG markers. Factor analysis was used for estimating a potentially lower number of unobserved synchrony factors. These common factors were then related to MMSE scores as well. Most markers displayed an initial increase of EEG synchrony with MMSE scores from 26 to 21 or 20, and a decrease below. This effect was most prominent during the cognitive task and may be owed to cerebral compensatory mechanisms. Factor analysis provided interesting insights in the synchrony structures and the first common factors were related to MMSE scores with coefficients of determination up to 0.433. We conclude that several of the proposed EEG markers are related to AD severity for the overall sample with a wide dispersion for individual subjects. Part of these fluctuations may be owed to fluctuations and day-to-day variability associated with MMSE measurements. Our study provides a systematic analysis of EEG synchrony based on a large and homogeneous sample. The results indicate that the individual markers capture different aspects of EEG synchrony and may reflect cerebral compensatory mechanisms in the early stages of AD.
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Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Sincronización Cortical/fisiología , Anciano , Anciano de 80 o más Años , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por ComputadorRESUMEN
OBJECTIVES: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival. METHODS: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment. RESULTS: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy. CONCLUSIONS: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy.
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Esclerosis Amiotrófica Lateral/epidemiología , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/mortalidad , Austria/epidemiología , Bases de Datos Factuales , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Factores Sexuales , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Parkinson's Disease (PD) is a neurodegenerative disease characterized by motor symptoms, but in which behavioral and cognitive disturbances are also common. Trust, due to its pervasiveness in society, has become a major research topic in several scientific disciplines. However, empirical evidence for trust behavior in neurological patients, and specifically for movement disorders such as PD, is missing. Evidence from healthy subjects, however, indicates that three brain regions are involved in trust perceptions and behavior, namely the limbic system, basal ganglia, and frontal cortex. PD affects all these brain regions. Therefore, we hypothesized that PD patients and healthy controls show differences in trust behavior. METHODS: We conducted an experiment using the trust game, an established paradigm to investigate trust behavior in both patient and healthy populations alike, controlling for risky decision making. Twenty patients suffering from PD diagnosed according to UK PDS Brain Bank criteria and twenty healthy controls (matched for age, gender, education, and income) were recruited. We excluded those suffering from clinically relevant neuropsychiatric comorbidities. RESULTS: We found that PD patients exhibit significantly lower levels of trust than do healthy controls. Importantly, our results cannot be explained by lower levels of risk-taking. Moreover, our results indicate that the trust deficit is independent of medication, disease duration, and severity of motor symptoms. CONCLUSION: Application of a standard procedure for measuring trust behavior revealed that PD patients exhibit lower levels of trust in other humans than do healthy controls. Against this background we make a call for further research to determine the underlying pathophysiology of reduced trust in PD.
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Conducta Cooperativa , Juegos Experimentales , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Confianza , Anciano , Ganglios Basales/fisiopatología , Encéfalo/fisiopatología , Estudios de Casos y Controles , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/psicología , Toma de Decisiones , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Recompensa , Riesgo , Asunción de RiesgosRESUMEN
Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy.
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Disfunción Cognitiva/complicaciones , Enfermedad de Parkinson/complicaciones , Inhibidores de la Colinesterasa/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Donepezilo/uso terapéutico , Humanos , Memantina/uso terapéutico , Rigidez Muscular/complicaciones , Rigidez Muscular/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Factores de Riesgo , Rivastigmina/uso terapéuticoRESUMEN
To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease.
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Mutación Missense , Enfermedad de Parkinson/genética , Proteínas de Transporte Vesicular/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Endosomas/genética , Endosomas/metabolismo , Femenino , Variación Genética , Haplotipos , Humanos , Enlace de Hidrógeno , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Linaje , Conformación Proteica , Proteínas de Transporte Vesicular/metabolismo , Red trans-Golgi/metabolismoRESUMEN
Recently a new autosomal dominant Parkinson's disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients.
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Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Proteínas de Transporte Vesicular/genética , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
OBJECTIVES: The neuroactive hormone oxytocin (OT) has significant influence on human behavior, and it has been measured peripherally in venous blood and in saliva in many behavioral neuroscience studies. Assessment of salivary hormone levels is popular due to non-invasiveness, but there is a controversy as to whether OT can be reliably measured in saliva and how possible time lags between plasma and salivary OT levels influence correlation. DESIGN AND METHODS: In order to shed light on the question whether salivary and plasma OT levels correlate, we designed an experiment where healthy young men had to look at a presentation of trustworthy faces on a computer screen (faces were taken from an established database in trust research). During three points in time, plasma and saliva samples were collected and analyzed using ELISA. RESULTS: Plasma and salivary OT levels did not correlate even when considering a time lag of 15 or 30 minutes. CONCLUSIONS: Our results suggest that plasma and salivary OT levels do not correlate in healthy young men, and hence comparison of results across plasma and salivary studies is neither informative nor warranted. However, we recommend replicating this study based on mixed-gender samples.