Diagnosis Of Neurodegenerative Diseases Research Articles

Effects on cerebral blood flow after single doses of the β2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, β-adrenoceptor (β-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant β2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, β2-AR agonist clenbuterol (20-160 μg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5mg), a β-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral β2-AR responses. Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3h after 20, 40, 80 and 160 μg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 μg clenbuterol were observed both without and with 5mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of β2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful β2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Early cortical atrophy in REM sleep behavior disorder

IntroductionThe presence of cortical atrophy (focal or diffuse) prior to the development of symptoms of cognitive impairment could predict the earliest cases of neurodegenerative disease in patients with CRSD. We reviewed the usefulness of cranial CT and MRI as early markers of cortical atrophy in patients with RSBD at our center. Patients and methodsRetrospective observational descriptive analysis of patients diagnosed with RSBD from October 2012 to October 2022. All with cranial CT or MRI, evaluated by a neuroradiologist. Results54 patients were included, 21 women (38.88%), 33 men (61.12%), mean age at diagnosis of TCSR: 69.04 ± 12.625. Of the 54 patients, 44 (81.48%) had imaging tests consistent with their age, and 10 had atrophy greater than expected for their age. Of the 54 patients, 21 (38.88%) with a diagnosis of neurodegenerative disease, 33 (61.12%) persist as idiopathic, almost all with more than 5 years of evolution (range of 1 to 10 years of evolution without diagnosis). Of the 10 (18.52%) patients with greater atrophy, all were diagnosed with neurodegenerative disease (8 in 1 year, 2 in 8 years). ConclusionsAlmost half of our series have developed a neurodegenerative disease in the first 10 years of evolution. The majority of them presented global cortical atrophy measured by the GCA scale in the first year of diagnosis, without other neurological symptoms. Patients who did not show cortical atrophy at diagnosis have not yet developed the neurodegenerative disease in 10 years of evolution. In our experience, the absence of cortical atrophy on cranial MRI or CT (measured by scales such as GCA) at the diagnosis of CRST seems to predict slower progression cases. These data should be corroborated with larger series.

Improved brain effective connectivity modelling by dynamic Bayesian networks

Background:If brain effective connectivity network modelling (ECN) could be accurately achieved, early diagnosis of neurodegenerative diseases would be possible. It has been observed in the literature that Dynamic Bayesian Network (DBN) based methods are more successful than others. However, DBNs have not been applied easily and tested much due to computational complexity problems in structure learning. New method:This study introduces an advanced method for modelling brain ECNs using improved discrete DBN (Improved- dDBN) which addresses the computational challenges previously limiting DBN application, offering solutions that enable accurate and fast structure modelling. Results:The practical data and prior sizes needed for the convergence to the globally correct network structure are proved to be much smaller than the theoretical ones using simulated dDBN data. Besides, Hill Climbing is shown to converge to the true structure at a reasonable iteration step size when the appropriate data and prior sizes are used. Finally, importance of data quantization methods are analysed. Comparison with existing methods:The Improved-dDBN method performs better and robust, when compared to the existing methods for realistic scenarios such as varying graph complexity, various input conditions, noise cases and non-stationary connections. The data used in these tests is the simulated fMRI BOLD time series proposed in the literature. Conclusions:Improved-dDBN is a good candidate to be used on real datasets to accelerate developments in brain ECN modelling and neuroscience. Appropriate data and prior sizes can be identified based on the approach proposed in this study for global and fast convergence.

Research progress on astrocyte-derived extracellular vesicles in the pathogenesis and treatment of neurodegenerative diseases.

Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles- both advantageous and disadvantageousin the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed.

Utilizing portable electroencephalography to screen for pathology of Alzheimer’s disease: a methodological advancement in diagnosis of neurodegenerative diseases

BackgroundThe current biomarker-supported diagnosis of Alzheimer’s disease (AD) is hindered by invasiveness and cost issues. This study aimed to address these challenges by utilizing portable electroencephalography (EEG). We propose a novel, non-invasive, and cost-effective method for identifying AD, using a sample of patients with biomarker-verified AD, to facilitate early and accessible disease screening.MethodsThis study included 35 patients with biomarker-verified AD, confirmed via cerebrospinal fluid sampling, and 35 age- and sex-balanced healthy volunteers (HVs). All participants underwent portable EEG recordings, focusing on 2-minute resting-state EEG epochs with closed eyes state. EEG recordings were transformed into scalogram images, which were analyzed using “vision Transformer(ViT),” a cutting-edge deep learning model, to differentiate patients from HVs.ResultsThe application of ViT to the scalogram images derived from portable EEG data demonstrated a significant capability to distinguish between patients with biomarker-verified AD and HVs. The method achieved an accuracy of 73%, with an area under the receiver operating characteristic curve of 0.80, indicating robust performance in identifying AD pathology using neurophysiological measures.ConclusionsOur findings highlight the potential of portable EEG combined with advanced deep learning techniques as a transformative tool for screening of biomarker-verified AD. This study not only contributes to the neurophysiological understanding of AD but also opens new avenues for the development of accessible and non-invasive diagnostic methods. The proposed approach paves the way for future clinical applications, offering a promising solution to the limitations of advanced diagnostic practices for dementia.

Label-Free Measurement of CD63 Positive Extracellular Vesicles Using Terahertz Chemical Microscopy.

Extracellular vesicles (EVs) are small cellular organelles involved in intracellular signaling and cell-to-cell interactions. Recent studies suggested that exosomes may have potential applications in the diagnosis and treatment of cancer and neurodegenerative diseases. In this study, extracellular vesicles of the human nonsmall cell lung cancer cell line H1299 and the unlabeled antiCD63 antibody were imaged using a new label-free terahertz chemical microscopy (TCM) technique to detect changes in the terahertz wave amplitude. To verify the high specificity of the protein biomarkers and the sensitivity of the biosensor surface, we also confirmed the selective binding of the antibody to the antigen, bovine serum albumin, and cancer cells. We also performed real-time measurements of the interaction between EVs from the H1299 cell and the antiCD63 antibody, which showed that the amount of change in the terahertz intensity increased with increasing concentration and the time to saturation decreased. Finally, to reuse the used biosensors (sensing plates), plasma-oxygen cleaning was used, and the activity of the biosensor surface was confirmed by terahertz microscopy and atomic force microscopy and was found to be reusable after less than 3 min of cleaning. Consequently, terahertz chemical microscopy was able to detect the presence or absence of antigen-antibody binding and its reaction rate and binding strength.

The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study.

Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging and neurodegenerative diseases. Our study employed a bidirectional two-sample Mendelian randomization (MR) design to assess the potential causal association between epigenetic aging and neurodegenerative diseases. We utilized publicly available summary datasets from several genome-wide association studies (GWAS). Our investigation focused on multiple measures of epigenetic age as potential exposures and outcomes, while the occurrence of neurodegenerative diseases served as potential exposures and outcomes. Sensitivity analyses confirmed the accuracy of the results. The results show a significant decrease in risk of Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, p = 0.03638). Additionally, we identified that HannumAge was linked to an increased risk of Multiple Sclerosis (OR = 1.0707, 95% CI 1.0056-1.1401, p = 0.03295). Furthermore, we also found that estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated an increased risk for Alzheimer's disease (OR = 1.0001, 95% CI 1.0000-1.0002, p = 0.04425). Beyond that, we did not observe any causal associations between epigenetic age and neurodegenerative diseases risk. The findings firstly provide evidence for causal association of epigenetic aging and neurodegenerative diseases. Exploring neurodegenerative diseases from an epigenetic perspective may contribute to diagnosis, prognosis, and treatment of neurodegenerative diseases.

Recent Progress in the Application of Tau Protein Biosensors for Diagnosis of Neurodegenerative Diseases.

The microtubule-associated Tau protein is found in the central nervous system (CNS) in six major isoforms. Neurodegenerative diseases have been linked to post-translational changes of Tau, most notably phosphorylation. Tau protein's molecular diversity is highly helpful in the identification of neurodegenerative illnesses. Nonetheless, one major obstacle to the early detection of brain illness is the nanoscale identification of tau proteins. The standard methods for identifying tau protein include western blotting, polymerase chain reaction (PCR), and real-time PCR. Enzyme-linked immunosorbent assay (ELISA) is another approach used. The limited sensitivity and specificity of these detections, together with the need for sophisticated equipment, are some of their drawbacks. The development of innovative and complex methods for tau protein screening is necessary to address the aforementioned issues. Biosensors are a cutting-edge instrument that may help identify various neurodegenerative biomarkers as early as feasible. This paper provides an overview of the most recent developments in the detection of neurodegenerative diseases employing biosensors built on nanotechnology and methods for imaging, electrochemical, and optical detection of the Tau protein. Furthermore, we outline the present difficulties and suggest a possible course for biosensor-based detection and intervention in the future.

Applications of magnetic resonance spectroscopy in diagnosis of neurodegenerative diseases: A systematic review

BackgroundMagnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in diagnosing neurodegenerative diseases because it is a relatively specialized technique that requires specialized equipment and expertise to perform and interpret. This systematic review aimed to present a comprehensive collection of MRS results in the most common neurodegenerative diseases. MethodsA systematic search of four electronic databases (PubMed, Scopus, Web of Science, and ScienceDirect) was conducted for studies published from 2017 to 2022. Articles that provided specific biomarker levels were selected, and studies that assessed the diseases via treatment, featured MRS applying nuclei other than 1H, or compared different animal models were excluded. ResultsA total of 25 articles, plus 3 articles for extra information in the introduction, were included in this review. Six of the most common neurodegenerative diseases, i.e., Alzheimer's and Parkinson's disease, Huntington chorea, ataxia, multiple sclerosis (MS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) were examined via MRS. The changes and ratios of N-acetylaspartate (NAA) could be seen in all of these disorders, which could lead to early diagnosis. However, there are other biomarkers, such as Cr and Chon, which can give convincing results. DiscussionThis observational study is the first synthesis of the latest evidence proving metabolic changes during neurodegenerative diseases using MRS as a diagnosis method. The findings indicate decreased N-acetylaspartate (NAA) and NAA/Cr ratios in Alzheimer's disease (AD), Parkinson's disease (PD), ataxias, and MS, reflecting neuronal loss or dysfunction. Increased choline and myo-inositol were noted in some studies, suggesting cell membrane turnover and neuroinflammation. Findings were less consistent for other metabolites like glutamate and gamma-aminobutyric acid. However, there were limitations due to the lack of studies on the same volumes of interest (VOIs) and the small number of participants.

The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.

Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders. We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model. The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001). These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden. PROSPERO (CRD42023437553).

Artificial intelligence in diagnosis of neurodegenerative disorders (literature review)

Currently, there are virtually no objective diagnostic signs (markers) to diagnose neurodegenerative diseases, that is why it may take months of constant monitoring of symptoms to establish a reliable diagnosis. Now there is an increasing number of reports that artificial intelligence can provide a more accurate diagnosis of neurodegenerative diseases by identifying specific diagnostic features from electroencephalography data, neuroimaging, and wearable devices and smartphones. This study reviews the application of artificial intelligence to the diagnosis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Using the international databases Scopus and PubMed, as well as the Russian Science Citation Index, we analysed studies that used artificial intelligence methods to detect, monitor, or control the progression of neurodegenerative diseases. The primary focus is on analysing electroencephalography data, neuroimaging data, and data from wearable devices and smartphones. The use of the latter may allow screening, diagnosis, and monitoring of the disease at home with a minimum economic cost. Artificial intelligence can be a useful tool for early, accurate, and non-invasive diagnosis of neurodegenerative diseases, as well as for assessing the effectiveness of treatment and predicting the course of the disease. However, for the widespread implementation of artificial intelligence in clinical practice, several issues related to the quality, availability, and standardization of data, validation and interpretation of results, ethical and legal aspects need to be resolved. The use of artificial intelligence requires both specialists from the IT industry with a deep understanding of the types and kinds of neural networks and physicians with fundamental knowledge of neurology, psychiatry, molecular biology, and biophysics.

Biomarkers of neuroinflammation in the diagnosis of traumatic brain injury and neurodegenerative diseases: a literature review

Biomarkers of neuroinflammation in the diagnosis of traumatic brain injury and neurodegenerative diseases: a literature review

Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.

Neurodegenerative diseases are still challenging clinical issues, with no curative interventions available and early, accurate diagnosis remaining difficult. Finding solutions to them is of great importance. In this review, we discuss possible exosomal diagnostic biomarkers and explore current explorations in exosome-targeted therapy for some common neurodegenerative diseases, offering insights into the clinical transformation of exosomes in this field. The burgeoning research on exosomes has shed light on their potential applications in disease diagnosis and treatment. As a type of extracellular vesicles, exosomes are capable of crossing the blood - brain barrier and exist in various body fluids, whose components can reflect pathophysiological changes in the brain. In addition, they can deliver specific drugs to brain tissue, and even possess certain therapeutic effects themselves. And the recent advancements in engineering modification technology have further enabled exosomes to selectively target specific sites, facilitating the possibility of targeted therapy for neurodegenerative diseases. The unique properties of exosomes give them great potential in the diagnosis and treatment of neurodegenerative diseases, and provide novel ideas for dealing with such diseases.

Modeling Neurodegeneration and Regeneration in Parkinson's Disease

The diagnosis and prevention of neurodegenerative diseases is a heavily examined topic in the neuroscience discipline. Whether it be from the anatomical and biological perspectives or the psychological and sociological perspectives, the ultimate goal is to discover strategies to pinpoint the infection as soon as possible. This article begins with reviewing the small-world network structure and then combines the sociological and anatomical perspectives to explain the progression of neuronal death within the brain by using rsfMRI data and the Hegselmann-Krause Model of Opinion Dynamics to illustrate critical interactions between brain regions, and to predict the ultimate behavior of the neural network after initial degeneration Following experimentation–in which critical regions related to Parkinson’s Disease were studied–thresholds were identified in specific regions which exhibited consistent converging behavior of the neural network toward either degenerative or regenerative directions. Furthermore, a simple graphical model is proposed to demonstrate the ranges of values in which current brain health could be of concern. We concluded that neuron death in one brain region can lead to further infection in the resulting system; however, some regions can also directly/indirectly compensate for the system’s decreased function. In future research endeavors, this could provide insight into developing more accurate predictive models for the goal of early detection of a diseased brain and its recovery.

Biomarkers of oxidative stress and proteopathies in the diagnosis of neurodegenerative diseases

Introduction. Despite numerous studies in the field of neurodegenerative diseases, the exact mechanisms of these processes have not yet been identified. The purpose of this review is to analyze the methodological approaches necessary to revise the traditional and create new reliable prognostic and diagnostic algorithms that reflect pathogenetic features at different stages of neurodegeneration and atypical course of the disease. Material and methods. The review highlights the results of clinical and experimental studies obtained using a complex of clinical, laboratory and instrumental methods with an emphasis on markers of oxidative stress and proteopathy. In preparing the materials, sources from international and domestic databases were used: Scopus, Web of Science, Pub Medline, RSCI mainly for the last 15 years. Results. An idea has been formed about the molecular mechanisms of neural tissue regression in a number of neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s disease. The relationship between the parameters of the oxidative process and the features of metal-energy shifts in organs and organ systems is demonstrated. The role of markers of oxidative stress in the early stages, when the process of inflammation prevails and in the atypical course of the disease, is shown. Valuable biochemical markers are cytokines, glutathione levels, myeloperoxidase activation, and isoprostanes. The review points to the prospect of including in screening indicators of iron and other metals such as Zn, Mg, affecting the clinic accumulation of β-amyloid, in connection with which they can be considered as the basis for the progression of neurodegeneration. New data on the contribution of halogenating stress to the pathogenesis of neuroinflammation are presented. An aspect requiring development in the field of biomarkers for assessing the duration of the disease and prognostic prospects is the data on the correlation of metabolic shifts in the intestinal microbiota with the duration of the disease and the inflammatory process. Essential for the creation of express diagnostic methods is the determination of redox balance as an integral marker in saliva, which has obvious advantages over the use of biological fluids, such as liquor and serum. Conclusion. The prospects of creating new prognostic and diagnostic schemes are associated with complexes, including laboratory and instrumental methods, in blood, liquor and saliva. Evaluation of the sensitivity and specificity of new markers depending on the clinical diagnosis allows the selection of pathogenetically significant markers in the early stages of the disease, with atypical neurodegeneration, to establish subtypes of the disease, to carry out their differential diagnosis.

The Olfactory Trail of Neurodegenerative Diseases.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits. Several prevalent neurodegenerative conditions, including impaired smell, arise in the early stages of Parkinson's and Alzheimer's diseases, presenting an attractive prospect as a snitch for early diagnosis. This review covers the current knowledge on the link between olfactory deficits and Parkinson's and Alzheimer's diseases. The review also covers the emergence of olfactory receptors as actors in the pathophysiology of these diseases. Olfactory receptors are not exclusively expressed in olfactory sensory neurons. Olfactory receptors are widespread in the human body; they are expressed, among others, in the testicles, lungs, intestines, kidneys, skin, heart, and blood cells. Although information on these ectopically expressed olfactory receptors is limited, they appear to be involved in cell recognition, migration, proliferation, wound healing, apoptosis, and exocytosis. Regarding expression in non-chemosensory regions of the central nervous system (CNS), future research should address the role, in both the glia and neurons, of olfactory receptors. Here, we review the limited but relevant information on the altered expression of olfactory receptor genes in Parkinson's and Alzheimer's diseases. By unraveling how olfactory receptor activation is involved in neurodegeneration and identifying links between olfactory structures and neuronal death, valuable information could be gained for early diagnosis and intervention strategies in neurodegenerative diseases.

Atrofia cortical precoz en el trastorno de conducta del sueño REM

IntroductionThe presence of cortical atrophy (focal or diffuse) prior to the development of symptoms of cognitive impairment could predict the earliest cases of neurodegenerative disease in patients with REM sleep behavior disorder (RSBD). We reviewed the usefulness of cranial CT and MRI as early markers of cortical atrophy in patients with RSBD at our center. Patients and methodsRetrospective observational descriptive analysis of patients diagnosed with RSBD from October 2012 to October 2022. All with cranial CT or MRI, evaluated by a neuroradiologist. Results54 patients were included, 21 women (38.88%), 33 men (61.12%), mean age at diagnosis of RSBD: 69.04±12.625 years. Of the 54 patients, 44 (81.48%) had imaging tests consistent with their age, and 10 had atrophy greater than expected for their age. Of the 54 patients, 21 (38.88%) with a diagnosis of neurodegenerative disease, 33 (61.12%) persist as idiopathic, almost all with more than 5years of evolution (range of 1 to 10years of evolution without diagnosis). Of the 10 (18.52%) patients with greater atrophy, all were diagnosed with neurodegenerative disease (8 in 1year, 2 in 8years). ConclusionsAlmost half of our series have developed a neurodegenerative disease in the first 10years of evolution. The majority of them presented global cortical atrophy measured by the GCA scale in the first year of diagnosis, without other neurological symptoms. Patients who did not show cortical atrophy at diagnosis have not yet developed the neurodegenerative disease in 10years of evolution. In our experience, the absence of cortical atrophy on cranial MRI or CT (measured by scales such as GCA) at the diagnosis of RSBD seems to predict slower progression cases. These data should be corroborated with larger series.

Neuropathology of the Neurodegenerative Diseases

A definite diagnosis of neurodegenerative diseases is required for neuropathological examination during an autopsy. Each neurodegenerative disease has specific vulnerable regions and affected systems (system degeneration), and is typified by an accumulation of abnormal protein with the formation of characteristic morphological aggregates in the nerve and glial cells, called proteinopathy. The most common neurodegenerative diseases are tauopathy, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD); α-synucleinopathy, including multiple system atrophy (MSA); and TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). PSP and CBD show characteristic tau-positive astrocytic inclusions known as tufted astrocytes and astrocytic plaques, respectively. PiD shows tau-positive neuronal inclusions termed Pick bodies. MSA is characterized by α-synuclein-positive oligodendroglial inclusions, called glial cytoplasmic inclusions. ALS- and FTLD-TDP show TDP-43-positive neuronal inclusions, such as skein-like and round inclusions. Huntington's disease shows polyglutamine-positive neuronal inclusions, and Creutzfeldt-Jakob disease shows diffuse deposition of granular prions in the neuropil. The atypical proteins in these diseases have abnormal conformational properties. A comprehensive comparison of the clinical findings and neuropathological observations, including neuroanatomy and images acquired during life, is important to improve the sensitivity of clinical diagnosis.

Atypical Structure of Broca's Area in a Patient with Primary Progressive Atrophy Syndrome at the Onset of Alzheimer's Disease

This article presents a clinical case of Alzheimer’s disease with a debut as primary progressive aphasia syndrome. Insufficient use of routine magnetic resonance imaging in this case in the diagnosis of neurodegenerative diseases and the advantage of such additional neuroimaging methods as positron emission tomography, functional magnetic resonance imaging with a scale assessment of atrophic changes. Additional neuroimaging techniques have been shown to significantly improve the early detection of pathological changes in brain structures and to reveal the location of functional areas involved in the neurodegenerative process.