Search

“Lines of flight are dragged behind you all your life.” Post-Memory, Old Age, and Forgetting in Ulrike Draesner’s Novel Sieben Sprünge vom Rand der Welt (2014) In contemporary German literature, particularly in the family novels that are key to the post-memory discourse of the past, there is a marked interest in the dysfunctions and deformations of memory associated with ageing processes. Demographic changes lead researchers to consider the determinants and the existing dominant themes and categories of interdisciplinary memory studies. Ulrike Draesner’s 2014 novel, Sieben Sprünge vom Rand der Welt, the subject of this paper, probes the meanders of memory and forgetting, examining their configurations in intergenerational relations. I am interested here in the threads that have been marginalized in the popular discourse on the flight and resettlement of millions of Germans from the eastern provinces of the Reich, which emerge along with the progressive dementia of one of the novel’s main characters.

Alzheimer's disease (AD) is an irreversible brain disorder associated with severe progressive dementia and is characterized by deposits of amyloid plaques in the brain. Over the past 20 years, the mortality of strokes and heart disease has decreased, but deaths from AD have increased. The four drugs used clinically to treat AD can only relieve symptoms but cannot slow the progression of the disease. Aducanumab, a human monoclonal antibody that preferentially binds to aggregated amyloid-β to reduce the number of amyloid plaques and slow disease progression, was approved to treat AD by the US Food and Drug Administration on June 7, 2021. It is the first disease-modifying therapy for AD, but there is considerable controversy regarding the drug's approval. Aducanumab offers hope for millions of patients.

To present a systematic review of published studies in databases such as PUBMED, REDALYC, SCIELO, DIALNET, SCOPUS, EBSCO and CONRICYT related to the role-played by the components present in the vegetable oil of grape seed (Vitis vinifera) and the prevention or delay in the onset or progression of neurodegenerative diseases. The analysis of the research revealed that neurodegenerative diseases causes alterations in consciousness or in the nervous system leading to severe damage in neuronal cells, these pathologies are considered gradual and progressive. Various syndromes manifest the degenerative diseases of the nervous system; in some of them the predominant symptom is the progressive dementia. Among the components of the diet that in numerous epidemiological studies have shown an inverse association are vitamins, minerals, carotenoids, polyunsaturated fatty acids and polyphenols, the latter being the ones addressed in this document. There is an important evidence that a nutritional support based on polyunsaturated fatty acids and antioxidants can be applied to subjects with a history of neurodegenerative conditions in order to act as neuroprotectors. This requires the determination of the nutritional benefits of these nutrients or of nutraceuticals for the health of this group of patients.

Background Adult-onset leukoencephalopathies are a group of heterogeneous disorders characterized by white matter abnormalities. Leukoencephalopathy is usually encountered in children, but here we report a case with adult-onset leukoencephalopathy. Also, we explore this concept of uncertainty in medicine by discussing the approach to this case that has multiple possible etiologies. Case presentation A 70-year-old Caucasian male presented with a subacute onset of cognitive impairment and mood disturbances associated with behavioral changes. Neuroimaging demonstrated high-intensity lesions involving cerebral white matter. Progressive dementia and cognitive decline followed. Multiple possible etiologies are discussed based on the patient presentation and risk factors. Conclusion Adult-onset leukoencephalopathy can become a diagnostic challenge. Certain approaches need to be developed to explore the uncertainty of such conditions and to improve diagnostic yield.

Variably protease-sensitive prionopathy (VPSPr) is a recently described sporadic prion disease with distinctive clinical and histopathological features. We report the clinical, imaging, and neuropathological features of VPSPr in a 46-year-old right-handed man who presented with progressive cognitive decline, behavior disturbances, and a 50-pound weight loss over 6 months. The initial evaluation revealed severe cognitive impairment with no focal neurologic deficits. His cognitive, psychiatric, and behavior symptoms progressed rapidly, and he died 12 months after the initial visit. Throughout his disease course, workup for rapid progressive dementia was unremarkable except that brain MRI diffusion-weighted imaging showed persistent diffuse cortical and thalamic signal abnormalities. Sporadic Creutzfeldt-Jakob disease was highly suspected; however, two EEGs (8 months apart) demonstrated only nonspecific cerebral dysfunction. The patient's CSF 14-3-3 protein was negative at the initial visit and again 8 months later. His CSF real-time quaking-induced conversion and total tau level were normal. An autopsy of his brain was performed, and the neuropathological findings confirmed VPSPr. Our case underlines the importance of considering VPSPr in the spectrum of prion disease phenotypes when evaluating individuals with rapidly progressive dementia.

Objectives The correlates of manic episodes in dementia have not been systematically studied. The primary goal of our study is to compare the sociodemographic characteristics and psychiatric comorbidities in Alzheimer’s dementia (AD) inpatients with manic episodes versus without manic episodes, and to evaluate the demographic predictors and risk factors for manic episodes in AD inpatients. Methods We conducted a case-control study using the Nationwide Inpatient Sample of 34,285 AD patients (age ≥60 years). Subsequently, the cases i.e., AD inpatients with a manic episode (N = 1,035) and the controls (without a manic episode, N = 1,035), were extracted using propensity-score matching based on age. The cases did not have a past psychiatric history of bipolar disorders. We used the logistic regression model to evaluate the odds ratio (OR) of association between pre-existing psychiatric comorbidities and manic episodes and evaluate the demographic predictors of manic episodes in AD inpatients. Results A higher proportion of AD inpatients with manic episodes were females (63.8%), whites (85.2%), and from low-income families below the 50th percentile (63%). Females were more likely to be hospitalized for manic episodes (OR 1.33; 95% CI 1.09-1.64) than males. AD inpatients with manic episodes had a higher risk of presenting with suicidal behaviors (OR 1.88; 95% CI 1.23-2.86). A significantly higher proportion of AD inpatients with manic episodes had comorbid tobacco use (5.3% vs. 3.4%) and cannabis use (1.4% vs. 0%) compared to those without manic episodes. Conclusion Females with AD had a greater risk of being hospitalized for manic episodes. These patients have an 88% higher risk of suicidal behaviors during the manic presentation and have comorbid tobacco and cannabis use. Early diagnosis and management of manic episodes in at-risk AD patients are important to improve the quality of life (QoL) and outcomes.

Creutzfeldt-Jakob Disease (CJD) is a rare invariably fatal neurodegenerative disease believed to be caused by an abnormal isoform of cellular infectious glycoprotein called prion protein. Though it is arare disease; yet it is the most common among prion diseases. Clinical presentation consists of rapidly progressive loss of memory, cognitive & visual disturbance, lack of coordination, myoclonus, cerebellar, pyramidal and extra pyramidal signs, akineticmutism & with progression of disease deterioration in higher mental functions become more pronounced. Periodic sharp triphasic wave complexes on EEG, high signal abnormalities in caudate nucleus and putamen on diffusion weighted (DW) or FLAIR MRI of Brain and positive 14-3-3 protein in CSF substantiate the diagnosis of CJD but definitive diagnosis is established by brain biopsy or autopsy materials. We report a case of 58-year old female patient who was admitted with complaints of rapidly progressive dementia, cognitive disturbance, blurring of vision and myoclonic jerks. Initial MRI brain and CSF findings were normal. Differential diagnoses that can present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease were considered after review of literature. In EEG triphasic wave complexes were seen, repeat DWMRI after two weeks showed bilateral hyper-intensities in basal ganglia involving caudate nucleus and putamen, suggesting a diagnosis of probable CJD on the basis of center for disease control and prevention (CDC) criteria. The case is reported because of its rarity and also to emphasise that patients with rapidly progressive dementia, associated visual and cognitive disturbances and myoclonus should be investigated with DW MRI, EEG&CSF for diagnosis of CJD.

Purpose of review To give an update on recent findings concerning the use of PET for differential diagnosis in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level. Recent findings Although accurate differential diagnosis of dementia can be achieved by imaging disease-specific patterns of cerebral glucose metabolism with [F]fluorodeoxyglucose ([F]FDG)-PET, the diagnostic impact of [F]FDG-PET in primary psychiatric disorders is limited. Amyloid-beta PET provides an incremental value beyond [F]FDG-PET in the differential diagnosis of dementia and was proposed as a biomarker defining the so-called Alzheimer continuum. Recently developed tau-specific tracers might also aid in the diagnostic process (biological definition of Alzheimer's disease together with amyloid-beta). Surpassing the diagnostic accuracy of other techniques, such as MRI, [F]FDG-PET has also gained widespread clinical use for diagnosis and follow-up of paraneoplastic and autoimmune disorders of the central nervous system (CNS) as an important differential diagnosis for rapid progressive dementia and subacute onset of psychiatric syndromes. Summary Molecular neuroimaging with PET is an established method for the differential diagnosis of neurodegenerative and autoimmune CNS disorders manifesting on a behavioural level with significant therapeutic and prognostic impact. Future prospective studies are needed to define the value of tau imaging for diagnosis and prognosis in neurodegenerative disorders.

Background & Objective: Diabetes and neurodegenerative diseases (ND) are progressive morbidities and represent a major public health burden. A growing body of evidence points towards the comorbidity of diabetes and NDs with a possible exacerbation of latter by former. Considering the high prevalence of both morbidities in aging world population, even a modest impact of diabetes on NDs could lead to significant public health implications. Several hypotheses and mechanistic evidence were proposed linking altered glucose metabolism to the risk of progressive dementia. Unregulated production of reactive oxygen species (ROS) and resultant oxidative stress (OS) are the common features of diabetes as well as NDs. Conclusion: This review explores the concept of altered glucose metabolic pathways leading to ROS increase and its possible link to NDs, with a special emphasis on Alzheimer’s diseases (AD). We also discuss the detailed mechanistic link between hyperglycemia, ROS generation, and neurodegeneration to highlight potential therapeutic avenues for better prevention and treatment.

Although rare, patients with variant Creutzfeldt-Jakob Disease (vCJD) in their differential diagnosis of progressive dementia and movement disorder could continue to present to hospitals for care. However, U.S.-based infection control guidelines do not fully address the possibility of vCJD. After near-misses involving increasing numbers of patients with clinical findings and epidemiologic risks compatible with vCJD, or exposures to chronic wasting disease, we sought to improve recognition and prevention of iatrogenic spread of these prion-related diseases.

Fritz Heinrich Lewy described the intracytoplasmic inclusions found in the neurons for the very first time. In 1919 these inclusions were termed as “LBs” by Tretiakoff. LBs were found in the brain of the patients suffering from Lewy body disease (LBD). LBD is characterized by the presence of Parkinsonian symptoms in the earlier stages and dementia in the later stages of the disease. LBs were classified on the basis of the region of the brain in which they are distributed and so is the case of the LBD means the type of the LBD depends on the anatomical areas of the brain involved. LBD is not a single disorder. It is a spectrum of disorders. This chapter addresses the entire profile of LBs, types, composition, formation, and various LB pathologies as well as diagnostic criteria and pharmacotherapy.

Made available in DSpace on 2020-12-12T02:10:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 Florida State University Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Known as a degenerative and progressive dementia, Alzheimer’s disease (AD) affects about 25 million elderly people around the world. This illness results in a decrease in the productivity of people and places limits on their daily lives. Electroencephalography (EEG), in which the electrical brain activity is recorded in the form of time series and analyzed using signal processing techniques, is a well-known neurophysiological AD biomarker. EEG is noninvasive, low-cost, has a high temporal resolution, and provides valuable information about brain dynamics in AD. Here, we present an original approach based on the use of quantile graphs (QGs) for classifying EEG data. QGs map frequency, amplitude, and correlation characteristics of a time series (such as the EEG data of an AD patient) into the topological features of a network. The five topological network metrics used here—clustering coefficient, mean jump length, betweenness centrality, modularity, and Laplacian Estrada index—showed that the QG model can distinguish healthy subjects from AD patients, with open or closed eyes. The QG method also indicates which channels (corresponding to 19 different locations on the patients’ scalp) provide the best discriminating power. Furthermore, the joint analysis of delta, theta, alpha, and beta wave results indicate that all AD patients under study display clear symptoms of the disease and may have it in its late stage, a diagnosis known a priori and supported by our study. Results presented here attest to the usefulness of the QG method in analyzing complex, nonlinear signals such as those generated from AD patients by EEGs. Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP) National Institute for Space Research (INPE) Earth System Science Center (CCST) Department of Neurology Psychology and Psychiatry Institute of Biosciences Botucatu Medical School São Paulo State University (UNESP) Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP) Department of Neurology Psychology and Psychiatry Institute of Biosciences Botucatu Medical School São Paulo State University (UNESP) CAPES: 2016/ 17914-3

Although dementia is not inevitable, mental decay does occur with aging, so the prevalence of dementia has risen as the lifespan of humans has increased. The global prevalence of dementia is now at pandemic proportions. In 2015, it was estimated that there were nearly 50 million people living with dementia, worldwide. This was projected to double every 20 years, reaching 75 million in 2030 and 132 million in 2050. Dementia is not a specific disease. It is a syndrome that affects memory, thinking, and social abilities severely enough to interfere with daily functioning. In the late 1800s, with advances in medicine and the ability to examine the brain with microscopes, it was realized that diseases could cause dementia. Alzheimer's disease is the most common cause of progressive dementia in adults. Over 100 years ago, Alzheimer, who dissected and studied the brains of affected people postmortem, saw microscopic amyloid plaques and neurofibrillary tangles. These neuropathological changes are now known to be characteristic of Alzheimer's disease. Although the concept of dementia has existed since time immemorial, the detailed mechanisms relevant to the neuroscience of dementia and its treatment are relatively recent discoveries. To aid further understanding, this chapter lists the resources on the regulatory and professional bodies, journals, books, and websites that are relevant to an evidence-based approach to the neuroscience of dementia.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in older individuals with specific neuropsychiatric symptoms. It is a proteinopathy, pathologically characterized by the presence of misfolded protein (Aβ and Tau) aggregates in the brain, causing progressive dementia. Increasing studies have provided evidence that the defect in protein-degrading systems, especially the autophagy-lysosome pathway (ALP), plays an important role in the pathogenesis of AD. Recent studies have demonstrated that AD-associated protein aggregates can be selectively recognized by some receptors and then be degraded by ALP, a process termed aggrephagy. In this study, we reviewed the role of aggrephagy in AD development and discussed the strategy of promoting aggrephagy using small molecules for the treatment of AD.

Over 5 million Americans and 50 million individuals worldwide are living with Alzheimer's disease (AD). The progressive dementia associated with AD currently has no cure. Although clinical trials in patients are ultimately required to find safe and effective drugs, animal models of AD permit the integration of brain pathologies with learning and memory deficits that are the first step in developing these new drugs. The purpose of the Alzheimer's Association Business Consortium Think Tank meeting was to address the unmet need to improve the discovery and successful development of Alzheimer's therapies. We hypothesize that positive responses to new therapies observed in validated models of AD will provide predictive evidence for positive responses to these same therapies in AD patients. To achieve this goal, we convened a meeting of experts to explore the current state of AD animal models, identify knowledge gaps, and recommend actions for development of next‐generation models with better predictability. Among our findings, we all recognize that models reflecting only single aspects of AD pathogenesis do not mimic AD. Models or combinations of new models are needed that incorporate genetics with environmental interactions, timing of disease development, heterogeneous mechanisms and pathways, comorbidities, and other pathologies that lead to AD and related dementias. Selection of the best models requires us to address the following: (1) which animal species, strains, and genetic backgrounds are most appropriate; (2) which models permit efficient use throughout the drug development pipeline; (3) the translatability of behavioral‐cognitive assays from animals to patients; and (4) how to match potential AD therapeutics with particular models. Best practice guidelines to improve reproducibility also need to be developed for consistent use of these models in different research settings. To enhance translational predictability, we discuss a multi‐model evaluation strategy to de‐risk the successful transition of pre‐clinical drug assets to the clinic.

The prion diseases, also known as transmissible spongiform encephalopathies (TSEs), represent a unique family of rare neurodegenerative disorders. They have much in common with other neurodegenerative diseases, but they are distinguished from all others by their highly transmissible nature. In addition, the host range of prion disease (PrD) is unusual in that animals, in addition to humans, can be affected and, as demonstrated by the experience of mad cow disease, prion disease can jump between species. Although the core features of these diseases include progressive dementia, ataxia, and variable neurological and psychiatric symptoms, several clinical and histopathologic phenotypes of disease are recognized. Despite this phenotypic variation, the etiology of all is traced to the misfolded isoform of a single protein known as the prion protein (PrP), a normal constituent of the plasma membrane of cells, especially neurons. There are several fascinating aspects of these diseases, including the origins of its discovery, the nature of its biology, and the future challenges for diagnosis and treatment. From sheep to cannibals to mad cows, the prion diseases have a rich and controversial history. Deciphering the molecular nature of prion generation and propagation will be key to developing a therapeutic approach to these diseases.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, fatal human prion disease that is characterized by progressive dementia and neurologic degeneration. It can mimic multiple other neurological disorders, and a high index of clinical suspicion is necessary to make a diagnosis. A 74-year-old woman with a 3-month history of a stroke and progressive neurologic deterioration was found to have sCJD. She expired within a week of her diagnosis. Autopsy revealed spongiform encephalopathy consistent with prion disease, and genetic analysis revealed 129 polymorphism and no pathologic mutation, confirming the diagnosis of nonfamilial human prion disease. No pathologic evidence of a stroke was found. Awareness of the disease by clinicians is important not only at the time of initial presentation but also during the following months. Since there is no treatment, invasive medical procedures should be limited to only those that are required for either diagnosis or hospice care.

Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years. Treatment was initiated at a dose of 30 mg, 100 mg, or 300 mg; all the patients then received the 300-mg dose for at least 96 weeks. The primary outcome was the time until a 2-point decline in the score on the motor and language domains of the CLN2 Clinical Rating Scale (which ranges from 0 to 6, with 0 representing no function and 3 representing normal function in each of the two domains), which was compared with the time until a 2-point decline in 42 historical controls. We also compared the rate of decline in the motor-language score between the two groups, using data from baseline to the last assessment with a score of more than 0, divided by the length of follow-up (in units of 48 weeks).Twenty-four patients were enrolled, 23 of whom constituted the efficacy population. The median time until a 2-point decline in the motor-language score was not reached for treated patients and was 345 days for historical controls. The mean (±SD) unadjusted rate of decline in the motor-language score per 48-week period was 0.27±0.35 points in treated patients and 2.12±0.98 points in 42 historical controls (mean difference, 1.85; P0.001). Common adverse events included convulsions, pyrexia, vomiting, hypersensitivity reactions, and failure of the intraventricular device. In 2 patients, infections developed in the intraventricular device that was used to administer the infusion, which required antibiotic treatment and device replacement.Intraventricular infusion of cerliponase alfa in patients with CLN2 disease resulted in less decline in motor and language function than that in historical controls. Serious adverse events included failure of the intraventricular device and device-related infections. (Funded by BioMarin Pharmaceutical and others; CLN2 ClinicalTrials.gov numbers, NCT01907087 and NCT02485899 .).

Amyloid plaques, along with neurofibrillary tangles, are a neuropathologic hallmark of Alzheimer disease (AD). Recently, amyloid PET radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disorders. In both research and clinical settings, amyloid PET imaging has provided important diagnostic and prognostic information for the management of patients with possible AD, mild cognitive impairment (MCI), and other challenging diagnostic presentations. Although the overall impact of amyloid imaging is still being evaluated, the Society of Nuclear Medicine and Molecular Imaging and Alzheimer's Association Amyloid Imaging Task Force have created appropriate use criteria for the standard clinical use of amyloid PET imaging. By the appropriate use criteria, amyloid imaging is appropriate for patients with (1) persistent or unexplained MCI, (2) AD as a possible but still uncertain diagnosis after expert evaluation and (3) atypically early-age-onset progressive dementia. To better understand the clinical and economic effect of amyloid imaging, the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study is an ongoing large multicenter study in the United States, which is evaluating how amyloid imaging affects diagnosis, management, and outcomes for cognitively impaired patients who cannot be completely evaluated by clinical assessment alone. Multiple other large-scale studies are evaluating the prognostic role of amyloid PET imaging for predicting MCI progression to AD in general and high-risk populations. At the same time, amyloid imaging is an important tool for evaluating potential disease-modifying therapies for AD. Overall, the increased use of amyloid PET imaging has led to a better understanding of the strengths and limitations of this imaging modality and how it may best be used with other clinical, molecular, and imaging assessment techniques for the diagnosis and management of neurodegenerative disorders.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self-catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion.METHODS AND STUDY DESIGN: A retrospective cohort study was performed, using data from the bi-national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis.RESULTS: We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred.DISCUSSION: Using data from a large, bi-national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted.

In 1906 the pathologist/psychiatrist Alois Alzheimer reported to a group of German psychiatrists the story of a 55-year-old woman who died after several years of progressive dementia, and in whose brain he had found both senile plaques and neurofibrillary tangles. Emil Kraepelin applied Alzheimer’s name to the newly described syndrome of dementia-plaques-tangles in the eighth edition of his important text Psychiatrie in 1910. Some cases of clinically typical Alzheimer’s disease are found to have plaques in a concentration consistent with disease but without tangles in the neocortex. The difference between neuron counts in early onset Alzheimer’s disease and age-matched normals is highly significant and very obvious. Silver stains of the Alzheimer neocortex display apparently broken neuritic processes, and this has been recognized for several decades. Since the mid 1980s and the isolation and sequencing of s-amyloid by G. G. Glenner, the majority of laboratory research on Alzheimer’s disease has centered on the peptide and its precursor protein amyloid precursor protein.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive dementia. Diffusion tensor imaging (DTI) has been used widely to delineate the white matter integrity/degeneration in AD. Automated fiber quantification (AFQ) method is a fully automated method, which can identify the major white matter fiber tracts and then evaluate the white matter properties. The main purpose of this study is to assess the white matter integrity and abnormities in a cohort of amnestic Mild Cognitive Impairment (aMCI) and AD patients as well as normal controls (NCs). We tested the utility of diffusion tensor imaging measures along white matter tracts as features to classify the AD from NCs using support vector machine. The results showed that we have detected credible and robust potential early biomarker that may be useful for clinical application in AD.

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease. It is clinically characterized by progressive dementia with increasing loss of memory, intellectual dysfunction, disturbances in speech, apraxia, agnosia, agitation, and restlessness. Early-onset AD (before age 65) versus late-onset AD might be distinguished.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive dementia. Diffusion tensor imaging (DTI) has been widely used to show structural integrity and delineate white matter (WM) degeneration in AD. The automated fiber quantification (AFQ) method is a fully automated method that can rapidly and reliably identify major WM fiber tracts and evaluate white matter properties. The main aim of this study was to assess WM integrity and abnormities in a cohort of patients with amnestic mild cognitive impairment (aMCI) and AD as well as normal controls (NCs). For this purpose, we first used AFQ to identify 20 major WM tracts and assessed WM integrity and abnormities in a cohort of patients with 120 participants (39 NCs, 34 aMCI and 47 AD) in the discovery dataset, as well as 122 participants (43 NCs, 37aMCI and 42 AD) in the replicated dataset. Pointwise differences along the WM tracts were identified in the discovery dataset and simultaneously confirmed by the replicated dataset. Next, we investigated the utility of DTI measures along WM tracts as features to classify patients with AD from NCs with multilevel cross validations using a support vector machine. The correlation analysis revealed that the identified impaired microstructural WM alterations and classification output were highly associated with cognitive ability in the patient groups, indicating that this credible, robust potential early biomarker may be useful for clinical application in AD. This systematic study provides a pipeline to examine WM integrity and its potential clinical application in AD and may be useful in studying other neurological and psychiatric disorders. Funding: This work was partially supported by the National Key Research and Development Program of China (No. 2016YFC1305904), the National Natural Science Foundation of China (Grant Nos. 81871438, 81571062, 81471120), and the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB32020200). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital.

International audience; Subacute cognitive disorders are frequently encountered in clinical practice, and many pathologies result in such presentations. Consequently, prompt and precise etiologic diagnosis is necessary because, in some cases, introducing treatments may reverse or prevent further progression of cognitive impairment. The differential diagnosis of subacute cognitive disorders is broad and requires careful consideration. Among the causes of such disorders are: Creutzfeldt-Jakob disease, a brain disorder resulting in a rapidly progressing dementia syndrome, myoclonus, psychiatric disorders, and visual hallucinations. Other etiologies include toxins and vitamin deficiencies, Wernicke-Korsakoff syndrome, psychiatric pathologies (e.g., bipolar or unipolar disorder and chronic psychosis, dissociative or nondissociative), and epileptic syndromes and nonconvulsive status epilepticus. Moreover, autoimmune encephalitis can cause cognitive dysfunction, often with co-occurring depressive syndrome, anxiety, and irritability (1). Patients with infectious encephalitis may present with symptoms of cognitive dysfunction as well.Here, we present a case of neurosyphilis in an HIV-negative male patient, with discussion of clinical manifestations and neuroimaging modification.

Positron emission tomography (PET) tracers play an important role in the diagnosis of Alzheimer’s disease, a condition that leads to progressive dementia and memory loss. A high binding affinity and specificity of the PET tracers to amyloid oligomers and fibrils are crucial for their successful application as diagnostic agents. In this sense, it is essential to design PET tracers with enhanced binding affinities, which can lead to more precise and earlier detection of Alzheimer’s disease conditions. The application of in silico methodology for the design and development of efficient PET tracers may serve as an important route to improved Alzheimer’s disease diagnosis. In this work, the performance of widely used computational methods is explored for predicting experimental binding affinities of styrylbenzoxazole (SB) derivatives against a common amyloid protofibril. By performing docking, molecular dynamics, and quantum chemistry calculations in sequence their combined predictive performance is explored. ...

Sporadic Creutzfeldt-Jakob disease (sCJD) is classified into six types based on codon 129 polymorphism in the PRNP gene and the protease-resistant prion-related protein, PrP [1,2]. This classification corresponds well with the clinical course and the pathological findings. MM2-cortical type sCJD (MM2C-sCJD) is clinically characterized by slow progressive dementia, increased levels of 14-3-3 protein in the cerebrospinal fluid (CSF), and no periodic synchronous discharge (PSD) in electroencephalography [3]. We report the case of a patient presented with chronic progressive cortical symptoms. Based on the initial clinical findings, corticobasal syndrome (CBS) was suspected although he did not develop akinetic mutism during the lifetime. The postmortem pathological and anatomical findings confirmed MM2C-sCJD. As per the existing diagnostic criteria, our case was difficult to diagnose during the patient’s lifetime. Therefore, this is an important case for considering future revisions of the diagnostic criteria for MM2C-sCJD.