Journal of Neural Transmission最新文献

Alzheimer's dementia is the main cause of cognitive impairment in people over the age of 65, with Alzheimer's disease starting presumably 10-15 years before the onset of clinical symptoms. It is therefore important to recognize dementia at an early stage and identify possible predictors. The existing methods, like different parameters of ß-Amyloid and Tau quantification in cerebrospinal fluid (CSF) or the living brain by measure of PET, are invasive and expensive. Therefore, the present study investigates the predictive value of a battery of clinical, neuropsychological, and blood parameters as well as two neurophysiological methods (functional near-infrared spectroscopy [fNIRS] and vagus somatosensory evoked potentials [VSEP]) which are easy to perform, less invasive and cost-efficient, for developing cognitive impairments in the elderly.In this longitudinal, prospective study, we enrolled 604 healthy participants between 70 and 77 years of age. The participants were invited back after a mean time interval of 3 years and 11 months, and after 7 years and 8 months, and their cognitive impairments were determined.Here we show that the development of cognitive impairments after approximately 8 years can be predicted not only by previously known risk factors such as ApoE4 risk alleles, dysosmia, or poor cognitive performance at baseline but that latency prolongation in the VSEP and altered functional activation patterns measured by NIRS at baseline also provide additional predictive value.We therefore suggest that both neurophysiological parameters, VSEP and NIRS, should be included in future studies, investigating the prediction of dementia. Dementia ClinicalTrials.gov Identifier: NCT02224326.

Essential tremor (ET) is characterized by upper limbs action tremor, sometimes extending to other body parts. However, ET can present with additional neurological features known as "soft signs." These signs of uncertain clinical significance are not sufficient to suggest an alternative neurological diagnosis, and include, among others, questionable dystonia and subtle voluntary movement alterations, i.e., bradykinesia and related features. This study aimed to explore the prevalence and relationship between questionable dystonia and subtle bradykinesia features in ET. Forty ET patients were video-recorded during clinical examination. Five movement disorder experts reviewed the videos to identify soft motor signs, i.e., dystonia and movement alterations during finger-tapping namely, (i) bradykinesia (reduced velocity), (ii) dysrhythmia, and (iii) sequence effect. Inter-rater agreement was quantified using the Fleiss' Kappa index. Data analysis was performed using nonparametric tests. We found a fair inter-rater agreement for upper limb dystonia (Fleiss' K = 0.27). Inter-rater agreement was higher (moderate) for head dystonia (Fleiss' K = 0.49) and finger-tapping assessment (Fleiss' K = 0.45). Upper limb dystonia was identified in 70% of patients, head dystonia in 35%, and finger-tapping alterations (in variable combinations) were observed in 95% of individuals (P < 0.001 by Fisher's exact test), including subtle bradykinesia and related features. No significant concordance or correlation was found between the soft signs. Subtle bradykinesia and related features are the most easily identifiable and frequent soft signs in ET, appearing in a higher percentage of patients than subtle dystonia. These findings provide insights into the clinical and pathophysiological understanding of ET.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.

Monoamine oxidase catalyzes oxidative deamination of monoamine transmitters and plays a critical role in the pathogenesis of neuropsychiatric diseases. Monoamine oxidase is classified into type A and B (MAO-A, MAO-B) according to the substrate specificity and sensitivity to inhibitors. The isoenzymes are different proteins coded by different genes localized on the X-chromosome, but they have identical intron-exon organization, similar protein structure and enzymatic mechanism and are considered to be derived from the same ancestral gene. The isoform-specific transcription organization regulates expression and function of MAO-A in response to cellular signaling pathways and environmental factors. MAO-A shows distinct properties and functions: isoform-specified polymorphisms, localization in catecholamine neurons, expression during early embryonic stage, regulation of brain architecture development and mediation of death and survival of neuronal cells. MAO-A is more flexible to genetic and environmental changes than MAO-B. Defective MAO-A expression impairs embryonic brain development and causes adult abnormal mood and behavior, as shown by human male cases with MAO-A deletion. This paper presents the regulation of brain MAO-A expression epigenetically by interaction between genetic and environmental factors. Association of aberrant MAO-A expression and activity with aggression, asocial behaviors, depressive disorders, and neurodegenerative diseases is discussed. Novel therapeutic strategy for psychiatric diseases by intervention to the regulation of MAO-A expression and activity is proposed.

Deep brain stimulation can influence the speech and voice quality in Parkinson´s disease (PD). This controlled, randomized, double-blind, cross-over clinical trial was conducted in 15 PD patients with bilateral subthalamic deep brain stimulation (DBS) to compare the effects of STN-DBS with combined subthalamic and nigral stimulation (STN + SNr-DBS) and DBS OFF on speech and voice parameters in PD patients. Speech and voice were analyzed subjectively using questionnaires (voice/pronunciation quality VAS, VHI, SHI) and objectively using audio analysis (maximum phonation time, AVQI, mean F0, intonation, syllable rate, reading time). Both stimulation conditions, STN + SNr-DBS and STN-DBS, revealed heterogeneous effects on speech and voice production with a slight beneficial effect on the voice quality of individual patients compared to DBS OFF, but not in the whole group. Small, but not significant effects were seen only in subjective voice quality on the VAS and intonation (both stimulation conditions compared to DBS OFF). No significant changes of the objective speech parameters during the audio analysis could be observed (both stimulation conditions compared to DBS OFF). There were no significant differences between STN + SNr-DBS and STN-DBS in any speech and voice domain. The beneficial effects on speech and voice production are minor in most patients compared to the motor improvements by DBS. Both STN-DBS and STN + SNr-DBS were safe, with comparable effects between both DBS modes, and represent no contraindications from the perspective of the voice specialist.

In this narrative review, we address mild cognitive impairment, a frequent complication of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs). Recent diagnostic criteria have blurred the lines between PD and dementia with Lewy bodies (DLB), particularly in the cognitive domain. Additionally, atypical parkinsonian syndromes like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) often present with significant cognitive decline. Even multiple system atrophy (MSA) can be associated with cognitive impairment in some cases. Several biomarkers, including imaging techniques, such brain magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), as well as pathological proteins either of the cerebrospinal fluid (CSF), such as Tau, amyloid beta, and synuclein, or of the serum, such as neurofilament light chain (Nfl) are more and more often utilized in the early differential diagnosis of APDs. The complex interplay between these conditions and the evolving understanding of their underlying pathologies highlight the need for further research to refine diagnostic criteria, possibly incorporate the new findings from the biomarker's field into the diagnostic criteria and develop targeted therapeutic strategies.

Objectives: It is common for patients with schizophrenia to exhibit symptoms of autism. Both autism spectrum disorders and schizophrenia share similar patterns of empathy deficits. This study purposed to explore the association between autistic features and empathy in Chinese patients with chronic schizophrenia.

Methods: We enrolled 857 patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS), Repeatable Battery for the Assessment of Neuropsychological 7 Status (RBANS), and Interpersonal Reactivity Index (IRI) were employed to assess the participants' clinical symptoms, neurocognition, and empathy, respectively. The severity of autistic symptoms was assessed with the PANSS Autism Severity Scale (PAUSS), with PAUSS scores ≥ 30 were considered to have significant autistic features.

Results: 114 schizophrenia patients (13.3%) had autistic features. Compared to schizophrenia patients without autistic features, those with autistic features had more severe clinical symptoms, and poorer neurocognition and empathic abilities. Female sex and empathic concerns were independently associated with autistic features in patients with chronic schizophrenia.

Conclusions: Our results suggest that autistic features tend to manifest quite commonly among patients with chronic schizophrenia. Empathy deficits are strongly associated with autistic features in patients with chronic schizophrenia, strengthening the view that autistic features may characterize a subgroup of schizophrenia patients.

Tools for the early diagnosis of neurocognitive disorders (NCD) both accessible, fast, fun and efficient are currently needed. A digit-tracking technique (Digitrack) has been developed based on the exploration of blurred images on a tablet with the finger, related to the exploration of images during eye-tracking. The present study aimed at assessing the objective usability and the subjective User eXperience (UX) of the Digitrack by older adults according to the presence and the severity of NCD. A total of 135 patients were included in a geriatric acute care unit. Objective usability was assessed through the number of patients able to complete the Digitrack's training (3 images) and evaluation (20 images) phases. UX was measured through standard questionnaires (AttrakDiff and meCUE), and through the description of engagement behaviors following an internally developed scale which included 5 levels (interactive, constructive, active, passive and disengaged behaviors). The success rate of the device was 94.1%. The Digitrack had a very good overall attractiveness, standard hedonic and pragmatic qualities, and the emotions perceived were predominantly positive. These findings were not homogeneously observed in the whole studied population. Patients highly impaired due to NCD tended to rate the device with more neutral scores and to perceive more negative emotions. The participants mainly demonstrated active behaviors, but patients with severe major NCD were mostly passive. The study showed promising results regarding the usability and acceptability of a digit-tracking technique within older adults. Further studies should evaluate the potential of this novel methods to make a cognitive diagnosis.

Quantitative susceptibility mapping (QSM) and transcranial sonography (TCS) offer proximal evaluations of iron load in the substantia nigra. Our prospective study aimed to investigate the relationship between QSM and TCS measurements of nigral iron content in patients with Parkinson's disease (PD). In secondary analyses, we wanted to explore the correlation of substantia nigra imaging data with clinical and laboratory findings. Eighteen magnetic resonance imaging and TCS examinations were performed in 15 PD patients at various disease stages. Susceptibility measures of substantia nigra were calculated from referenced QSM maps. Echogenicity of substantia nigra on TCS was measured planimetrically (echogenic area) and by digitized analysis (echo-intensity). Iron-related blood serum parameters were measured. Clinical assessments included the Unified PD Rating Scale and non-motor symptom scales. Substantia nigra susceptibility correlated with echogenic area (Pearson correlation, r = 0.53, p = 0.001) and echo-intensity (r = 0.78, p < 0.001). Individual asymmetry indices correlated between susceptibility and echogenic area measurements (r = 0.50, p = 0.042) and, more clearly, between susceptibility and echo-intensity measurements (r = 0.85, p < 0.001). Substantia nigra susceptibility (individual mean of bilateral measurements) correlated with serum transferrin saturation (Spearman test, r = 0.78, p < 0.001) and, by trend, with serum iron (r = 0.69, p = 0.004). Nigral echogenicity was not clearly related to serum values associated with iron metabolism. Susceptibility and echogenicity measurements were unrelated to PD duration, motor subtype, and severity of motor and non-motor symptoms. The present results support the assumption that iron accumulation is involved in the increase of nigral echogenicity in PD. Nigral echo-intensity probably reflects ferritin-bound iron, e.g. stored in microglia.

Recent advancements in neurology have shifted focus from mere diagnosis to comprehensive management of movement disorders, particularly Parkinson's Disease (PD), which is rapidly increasing in prevalence due to global ageing trends. While age is a key risk factor for PD, centenarians often exhibit a remarkably low prevalence of the disease, presenting an intriguing paradox. This viewpoint explores potential reasons for this low prevalence, drawing on studies from regions with high centenarian populations, known as Blue Zones. The authors highlight the importance of genetic, lifestyle, and environmental factors in promoting healthy ageing and examines how these may contribute to the resilience against PD found in centenarians. By understanding the protective mechanisms in centenarians, particularly the concept of hormesis and factors like diet, exercise, and social connections, we may inform prevention strategies for PD. The study proposes the "EAT, MOVE, SLEEP, PROTECT, and REPEAT" approach as a framework for lifestyle interventions to counteract PD risk factors. Ultimately, centenarians offer valuable insights into delaying neurodegeneration, providing a model for potential preventive trials for PD.