Frontal Dementia Research Articles

N-BodyPat: Investigation on the dementia and Alzheimer's disorder detection using EEG signals

The N-body problem is a remarkable research topic in physics. We propose a new feature extraction model inspired by the N-body trajectory and test its feature extraction capability. In the first part of the research, an open-access electroencephalogram (EEG) dataset is used to test the proposed method. This dataset has three classes, namely (i) Alzheimer's Disorder (AD), (ii) frontal dementia (FD), and (iii) control groups. In the second step of the study, the EEG signals were divided into segments of 15 s in length, which resulted in 4,661 EEG signals. In the third part of the study, the proposed new self-organized feature engineering (SOFE) model is used to classify the EEG signals automatically. For this SOFE, two novel methods were presented: (i) a dynamic feature extraction function using a graph of the N-Body orbital, termed N-BodyPat, and (ii) an attention pooling function. A multileveled and combinational feature extraction method was proposed by deploying both methods. A feature selection function using ReliefF and Neighborhood Component Analysis (RFNCA) was used to choose the most informative features. An ensemble k-nearest neighbors (EkNN) classifier was employed in the classification phase. Our proposed N-BodyPat generates seven feature vectors for each channel, and the utilized EEG signal dataset contains 19 channels. In this aspect,133 (=19 × 7) EkNN-based outcomes were created. To attain higher classification performance by employing these 133 EkNN-based outcomes, an iterative majority voting (IMV)-based information fusion method was applied, and the most accurate outcomes were selected automatically. The recommended N-BodyPat-based SOFE achieved a classification accuracy of 99.64 %.

The “Eye of the tiger sign” in Progressive Supranuclear Palsy: Is it a coincidence or not?

Progressive supranuclear palsy (PSP); is a neurodegenerative disorder involved in atypical parkinsonism syndromes. The classical clinical presentation is postural instability, falls, downward paralysis, frontal dementia, and symmetric akinetic-rigid parkinsonism. The atrophy of the mesencephalon in magnetic resonance imaging (MRI) is an important marker in diagnosing the disease. Recently, a few PSP cases reported the “eye of the tiger” sign on MRI. The “eye of the tiger” sign, in globus pallidus, is a sign that bilaterally symmetrically located low signal intensity and central longitudinal hyperintensity are observed. While previously a specific finding for the pantothenate kinase-associated neurodegeneration (PKAN), it is no longer considered specific because of the reported cases of non-PKAN with the “eye of the tiger” sign such as neuropherritinopathy, multi-system atrophy, corticobasal degeneration. In this report, we aimed to contribute to the literature by presenting two PSP cases in which the “eye of the tiger” sign was observed.

Features of cognitive impairment and anxiety-depressive disorders in patients in the acute period of stroke

Introduction. Cognitive impairment after a stroke remains one of the leading causes of disability. Despite the introduction of new methods of treatment, diagnosis, and prevention of acute vascular diseases, more than 50 % of patients experience cognitive disorders after a stroke, a third of which reach a severe degree of dementia. The purpose of the study is to identify and assess risk factors for the development of cognitive impairment disorders in patients after a stroke and evaluate the impact of anxiety and depressive phenomena on their course. Materials and methods. The combined retro-prospective study included 40 patients with mild stroke according to the NIHSS. The diagnosis of stroke in all subjects was verified based on the results of MSCT of the brain. All patients underwent a comprehensive clinical and laboratory monitoring: a general examination; an assessment of neurological and functional status; an assessment of cognitive functions and mental status by MMSE scale and the Frontal Assessment Battery; an assessment of anxiety-depressive disorders by the Spielberger State-Trait Anxiety Inventory, the Beck Depression Inventory, and the Hamilton Rating Scale. The influence of individual risk factors on the development of cognitive impairment was evaluated. Results. More than 80 % of the patients with mild stroke in the acute period experienced a decrease in cognitive functions, while 62 % of the subjects showed signs of frontal dementia of varying severity. In the presence of high comorbidity with forms of the circulatory system pathologies (hypertension, diabetes, atrial fibrillation, coronary heart disease), there was a high frequency of both frontal dementia (in 87 % of the patients), and a decrease in cognitive functions on the MMSE scale (67 % of cases). All patients were diagnosed with depression, and half of them — with severe depression. 80 % of the patients with severe depression had severe cognitive changes on the MMSE scale, and 75 % had severe frontal dysfunction. Conclusion. Thus, high vascular comorbidity and the presence of anxiety and depressive disorders are significant risk factors for the development of cognitive impairment after a stroke. In this regard, measures aimed at their timely detection, treatment, and correction will make it possible to effectively reduce the incidence of post-stroke cognitive impairment, which, in turn, will improve the quality of life not only for the patients themselves but also for their relatives.

Difficulties in diagnosing progressive supranuclear palsy

Progressive supranuclear palsy is a sporadic neurodegenerative disease manifested by oculomotor disorders, akinetic- rigid syndrome, early development of postural instability, gradual development of frontal dementia, and pseudobulbar syndrome. Diagnosis of PNP is determined by the specifi c topical distribution of the degenerative lesion in the brain. This article describes a clinical case of a 67-year-old patient with PNP, a feature of which is the complexity of diff erential diagnosis, given the presence of a variety of comorbidities.

A homozygous variant in CHMP3 is associated with complex hereditary spastic paraplegia

BackgroundMonogenic neurodegenerative diseases represent a heterogeneous group of disorders caused by mutations in genes involved in various cellular functions including autophagy, which mediates degradation of cytoplasmic contents by their transport...

MAO-B İnhibitörü Kullanan Progresif Supranükleer Palsi’li Hastada Spinal Anestezi Deneyimi

Progressive supranuclear palsy (PSP) is a rare clinical syndrome characterized by postural instability and mild dementia. The classical clinical picture of PSP includes severe gait and balance disorder, general bradykinesia, frontal dementia, visual disorders, dysarthria and dysphagia. Aspiration pneumonia is the leading cause of death in advanced PSP. We aimed to present our experiences in a 72-year-old patient with PSP using MAO-B inhibitor as an update for anaesthesiologists. We recommend that it should be taken into consideration that patients with PSP have a high risk of aspiration due to dysphagia and use of various medical treatments with high drug interaction and regional anaesthesia should be preferred. At the same time, we recommend the careful use of opioids during general or regional anaesthesia if the drug cannot be discontinued in patients using MAO-B inhibitor.

Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia.

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p < 0.001). And IL-6 was evaluated in the schizophrenia group (p < 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia.

Atypical Presentations of Alzheimer’s Disease: Beyond Amnestic Dementia

Neuropathological and biomarker-based studies indicate that Alzheimer’s disease may sometimes present not with the typical amnestic dementia syndrome of the hippocampal type but with atypical clinical pictures. Atypical presentations include frontal dementia sometimes with additional behavioural component mimicking frontotemporal dementia, logopenic primary progressive aphasia and posterior cortical atrophy, while mixed presentations include patients with additional vascular or Lewy body pathology. More atypical presentations include non-logopenic (semantic, non-fluent agrammatic and unclassifiable) primary progressive aphasia, corticobasal syndrome and cases mixed with normal pressure hydrocephalus. Atypical clinical presentations of Alzheimer’s disease may be more common than previously thought. Cerebrospinal fluid levels of biomarkers such as amyloid beta peptide, hyperphosphorylated tau protein and total tau protein, may offer a useful tool for correct ante mortem identification of such patients, which is likely to affect therapeutic decisions.

Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene.

The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer’s disease, vascular dementia, and frontotemporal dementia. Inflammation, PI3K-AKT, and ubiquitin-mediated proteolysis were identified as the main pathways that are dysregulated in these dementias. All of these dementias are regulated by 12 shared transcription factors. Protein–chemical interaction network analysis of dementia switch genes revealed that valproic acid may be neuroprotective for these dementias. Collectively, we identified shared and unique dysregulated gene expression, pathways and regulatory factors among dementias. New key mechanisms that lead to the development of dementia were revealed and it is expected that these data will advance personalized medicine for patients.

Can behavioral symptoms differentiate cortical from subcortical dementia - A comparative study of behavioral profile of Parkinson’s disease dementia and behavioral variant of frontotemporal dementia

Patients of behavioural variant of frontotemporal dementia (bvFTD) exhibit prominent behavioural abnormalities along with executive dysfunction. Whereas executive dysfunction is also common in subcortical dementias because of disturbance in fronto-subcortical connection, behavioural symptoms are less frequent. To determine the frequencies of behavioural symptomatology of patients with subcortical (Parkinson's disease with dementia or PDD) and frontal cortical dementia (behavioural variant of Frontotemporal dementia or bvFTD) and to find out the discriminating value of behavioural characteristics in differentiating these two group of patients. Patients were consecutively recruited from Cognitive and Movement Disorder Clinics following standard diagnostic criteria. A total 20 bvFTD and 20 PDD patients were recruited. Behavioural symptoms were noted from reliable caregiver following the questionnaire prepared by Bathgate et al. (2000). Whereas eating and vegetative behaviour were more frequent in bvFTD (85% vs 45%, p = 0.018), the neuropsychiatric behaviours were more common in PDD group 80.0% vs 50.0%, p = 0.095). Although didn’t achieve statistical significance, other symptoms found to be discriminating in two condition were (i) sensory behaviour (p = 0.056), (ii) cognitive mediated behaviour (p = 0.794), (iii) affect-social behaviour (p = 0.162), and (iv) compulsion-ritual behaviour (p = 0.33). The behaviour related to environmental dependency were not found prominent in either groups (p = 0.155), although utilization behavior and echopraxia were more common in bvFTD. Behavioural abnormalities were more common in bvFTD group with prominent abnormality in eating & vegetative behaviour, sensory behaviour, cognitive mediated behaviour, affect-social behaviour, compulsion-ritual behaviour and the PDD group showed marked neuropsychiatry behavioural abnormalities.

Progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized pathologically by 4 repeat tau deposition in various cell types and anatomical regions. Richardson's syndrome (RS) is the initially described and one of the clinical phenotypes associated with PSP pathology, characterized by vertical supranuclear gaze paly in particular downwards, postural instability with early falls and subcortical frontal dementia. PSP can manifest as several other clinical phenotypes, including PSP-parkinsonism, -pure akinesia with gait freezing, -frontotemporal dementia, - corticobasal syndrome, - speech/language impairment. RS can also have a pathologic diagnosis other than PSP, including corticobasal degeneration, FTD-TDP-43 and others. New clinical diagnostic criteria take into account this phenotypic variability in an attempt to diagnose the disease earlier, given the current lack of a validated biomarker. At present, therapeutic options for PSP are symptomatic and insufficient. Recent large neuroprotective trials have failed to provide a positive clinical outcome, however, have led to the design of better studies that are ongoing and hold promise for a neuroprotective treatment for PSP.

History of Pick's disease

History of Pick's disease

Prediction of motor neuron disorder in frontotemporal lobar degeneration

Background: Recent research has raised the awareness of frontotemporal lobar degeneration (FTLD). The phenotypes and genotypes of FTLD are quite diverse. One of the phenotypes of FTLD is regarding motor neuron disorder developing in patients with certain frontal predominant dementia.

THE MINI EATING BEHAVIOR INVENTORY (MINI EBI): A 10-ITEM CLINICAL TOOL FOR THE EARLY DIAGNOSIS OF FRONTOTEMPORAL DEMENTIA

Changes in eating behaviors and food preference are very frequent in patients with frontotemporal dementia. Despite a specific pattern, this behavioral change is not used as a diagnosis tool. In this study we proposed a short version of a caregiver questionnaire named Mini Eating Behavior Inventory (Mini-EBI). The first EBI questionnaire consisted in 30 questions investigating four domains of eating behaviors (eating habits, food preference, table manners, and swallowing problems). This 30-item questionnaire allowed to distinguish frontotemporal dementia from Alzheimer's disease with high sensitivity and specificity. The aim of this study was to test a 10-item version of the questionnaire, called Mini-EBI. Two groups of patients were studied using the Mini-EBI: 50 patients with frontal variant frontotemporal dementias (fv-FTD) and 40 patients with Alzheimer's diseases (AD) confirmed by CSF biomarkers. Results showed that the Mini-EBI scores were significantly different in the two groups with mean scores (± SD) of 6.2 / 10 (± 1.9) in fv-FTD patients and 1 /10 (± 1.3) in AD patients. The ROC curves analyzes showed a high area under the curve (AUC = 0.98, p<0.0001) and revealed a best cut-off value of > 3 /10 for fv-FTD diagnosis, with 96.9 % sensitivity and 90.9 % specificity. The Mini-EBI, shown as a rapid and simple 10-item caregiver questionnaire, could be proposed as a new diagnosis tool distinguishing fv-FTD patients from AD patients.

Characterization of an FTLD-PDB family with the coexistence of SQSTM1 mutation and hexanucleotide (G4C2) repeat expansion in C9orf72 gene

The C9orf72 expansion is considered a major genetic cause of familial frontotemporal dementia (FTD) in several patients' cohorts. Interestingly, C9orf72 expansion carriers, present also abundant neuronal p62-positive inclusions. Although p62/SQSTM1 mutations were initially associated with Paget disease of bone (PDB), they have been also identified in FTD. We describe an FTD-PDB family in which the proband presented with behavioral FTD phenotype and concomitant Paget disease. The molecular genetic analysis revealed the co-occurrence of 2 mutations; the pathogenic C9orf72 expansion and p.P392L heterozygous missense mutation in SQSTM1 gene. Amongst the 6 family members analyzed, the p.P392L SQSTM1 mutation segregated as expected with PDB, whereas the C9orf72 expansion segregated with frontal cognitive impairment or dementia in all but one carrier. The coexistence of these conditions could be underestimated since neither patients with FTD nor patients with PDB undergo bone scintigraphy or cognitive assessment, respectively. The number of cases with double mutations could also be over looked as the molecular strategy adopted in most laboratories ends with the identification of one pathogenic mutation in one of the known causative genes. Therefore, we advocate for further clinical and molecular evaluation in suspect cases.

The phenotypic spectrum of progressive supranuclear palsy

Traditionally, the clinical picture of progressive supranuclear palsy (PSP) was defined by early postural instability with falls, supranuclear vertical gaze palsy, symmetric akinesia and rigidity, frontal and subcortical dementia, and pseudobulbar palsy, leading to death after a mean disease duration of approximately six years. A definite diagnosis of PSP depends on neuropathological confirmation. In recent years, clinico-pathological studies have drawn attention to various “atypical” clinical manifestations of PSP. In these, a clinical diagnosis of PSP is delayed or never accomplished. Comprehensive understanding of the natural history of PSP is required to permit an early and accurate diagnosis. Based on current evidence, this review provides an update on the clinical spectrum of PSP.

Dementia DSM-IV/ICD-10 or neurocognitive disorder DSM-5?

Background and Objectives: According to existing data the term dementia was invented in the first century BC. It was introduced in the European literature in the 17th and 18th centuries AC. At the end of the 17th century, the French Encyclopedia points at ethiological implications which would later shape legal concepts. In the 19th century the Centroeuropean research develops specific nosologies until, in the 20th centu- ry, senile dementia is gradually discredited. Methods: Slightly over ten years ago, the Mild Cognitive Disorder (MCD) conceptual- ization was introduced as an early stage of Alzheimer’s disease (AD), but the lack of co- herence in relation to lesions sparked a still ongoing controversy, as the author of the MCD concept belongs to the Writing Board of DSM 5. Results : The DSM IV focuses on a categorical approach in spite of the difficulty in dif- ferentiating “normal” from “pathological” impairment at certain ages. On the other hand, the DSM 5 adopts the Dimensional System with a Mild or Severe Neurocognitive Disor- der definition, which is necessarily arbitrary and imposes a statistical criterion. The wide- spread use of this classification would imply diagnosing a large proportion of the popula- tion with huge social and medical implications. This triggered a variety of reactions, such as the APA note which claims that DSM 5 and CIE-10 “virtually contain the same codes”. However a WHO study revealed that 70% of surveyed psychiatrists used CIE 10 criteria. Conclusions: The DSM 5 gives weight to cognitive aspects using as a severity criterion the number of standard deviations in relation to psychometric normality. It might be mis- leading if applied to some forms of dementia, for instance frontal dementias. The CIE-10 and DSM IV criteria are more operational.

Staining neurons with Golgi techniques in degenerative diseases of the brain.

Staining neurons with Golgi techniques in degenerative diseases of the brain.

Current research, diagnosis, and treatment of fragile X-associated tremor/ataxia syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by a premutation CGG-repeat expansion in the 5'UTR of the fragile X mental retardation 1 (FMR1) gene. The classical clinical manifestations include tremor, cerebellar ataxia, cognitive decline and psychiatric disorders. Other less frequent features are peripheral neuropathy and autonomic dysfunction. Cognitive decline, a form of frontal subcortical dementia, memory loss and executive function deficits are also characteristics of this disorder. In this review, we present an expansion of recommendations for genetic testing for adults with suspected premutation disorders and provide an update of the clinical, radiological and molecular research of FXTAS, as well as the current research in the treatment for this intractable complex neurodegenerative genetic disorder.

191st ENMC International Workshop: Recent advances in oculopharyngeal muscular dystrophy research: From bench to bedside 8-10 June 2012, Naarden, The Netherlands

This workshop hosted a group of 19 clinicians and basic scientist from 5 countries (France, USA, Canada, Denmark and The Netherlands). Recent research developments and possible collaboration in advancing therapies for oculopharyngeal muscular dystrophy (OPMD), a late onset, rare and progressive neurodegeneration disorder were discussed in this meeting. The disease is caused by alanine expansion mutations in the gene encoding for poly(A)-binding protein nuclear 1 (PABPN1), resulting in accumulation of mutant PABPN1 in the cell nucleus and the formation of insoluble aggregates. Therefore, OPMD is categorized together with neurodegenerative disorders that are caused by single amino acid repeats. While the genetic cause for those disorders is often recognized, the molecular basis for symptoms is still obscure. PABPN1 is ubiquitously expressed and it is not known why symptoms develop only after midlife and initially only in subsets of skeletal muscles [1,2]. While the genetic cause for OPMD was reported in 1998 and good surgical treatments exist for major early symptoms, there are currently no medical options for the more general skeletal muscle involvement, no validated biomarkers and no clinical severity scale.