Alzheimer’s electroencephalogram event scalp and source localization

Alzheimer’s disease is the most common cause of dementia which causes a progressive and irreversible impairment of several cognitive functions. The aging population has been increasing significantly in recent decades and this disease affects mainly the elderly. Its diagnostic accuracy is relatively low and there is not a biomarker able to detect AD without invasive tests. Despite the progress in better understanding the disease there remains no prospect of cure at least in the near future. The electroencephalogram (EEG) test is a widely available technology in clinical settings. It may help diagnosis of brain disorders, once it can be used in patients who have cognitive impairment involving a general decrease in overall brain function or in patients with a located deficit. This study is a new approach to improve the scalp localization and the detection of brain anomalies (EEG temporal events) sources associated with AD by using the EEG.

Electroencephalogram cepstral distances in alzheimer’s disease diagnosis

Alzheimer's disease (AD) represents one ofthe greatest public health challenges worldwide nowadays, because it affects millions of people ali o ver the world and it is expected that the disease will increase considerably in the near future. This study is the first application attempt of cepstral analysis on Electroencephalogram (EEG) signals to find new parameters in arder to achieve a better differentiation belween EEGs of AD patients and Control subjects. The results show that the methodology that uses a combined Wavelet (WT) Biorthogonal (Bior) 3.5 and cepstrum analysis was able to describe the EEG dynamics with a higher discriminative power than the other WTs/spectmm methodologies m previous studies. The most important significance figures were found in cepstral distances between cepstrums oftheta and alpha bands (p=0. 00006<0. 05).

Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice

AIMS: Cognitive decline in Alzheimer's disease (AD) patients has been linked to synaptic damage and neuronal loss. Hyperphosphorylation of tau protein destabilizes microtubules leading to the accumulation of autophagy/vesicular material and the generation of dystrophic neurites, thus contributing to axonal/synaptic dysfunction. In this study, we analyzed the effect of a microtubule-stabilizing compound in the progression of the disease in the hippocampus of APP751SL/PS1M146L transgenic model. METHODS: APP/PS1 mice (3 month-old) were treated with a weekly intraperitoneal injection of 2 mg/kg epothilone-D (Epo-D) for 3 months. Vehicle-injected animals were used as controls. Mice were tested on the Morris water maze, Y-maze and object-recognition tasks for memory performance. Abeta, AT8, ubiquitin and synaptic markers levels were analyzed by Western-blots. Hippocampal plaque, synaptic and dystrophic loadings were quantified by image analysis after immunohistochemical stainings. RESULTS: Epo-D treated mice exhibited a significant improvement in the memory tests compared to controls. The rescue of cognitive deficits was associated to a significant reduction in the AD-like hippocampal pathology. Levels of Abeta, APP and ubiquitin were significantly reduced in treated animals. This was paralleled by a decrease in the amyloid burden, and more importantly, in the plaque-associated axonal dystrophy pathology. Finally, synaptic levels were significantly restored in treated animals compared to controls. CONCLUSION: Epo-D treatment promotes synaptic and spatial memory recovery, reduces the accumulation of extracellular Abeta and the associated neuritic pathology in the hippocampus of APP/PS1 model. Therefore, microtubule stabilizing drugs could be considered therapeutical candidates to slow down AD progression. Supported by FIS-PI12/01431 and PI15/00796 (AG),FIS-PI12/01439 and PI15/00957(JV)

A qualitative impairment in face perception in Alzheimer’s disease : evidence from a reduced face inversion effect

Prevalent face recognition difficulties in Alzheimer’s disease (AD) have typically been attributed to the underlying episodic and semantic memory impairment. The aim of the current study was to determine if AD patients are also impaired at the perceptual level for faces, more specifically at extracting a visual representation of an individual face. To address this question, we investigated the matching of simultaneously presented individual faces and of other nonface familiar shapes (cars), at both upright and inverted orientation, in a group of mild AD patients and in a group of healthy older controls matched for age and education. AD patients showed a reduced inversion effect (i.e., larger performance for upright than inverted stimuli) for faces, but not for cars, both in terms of error rates and response times. While healthy participants showed a much larger decrease in performance for faces than for cars with inversion, the inversion effect did not differ significantly for faces and cars in AD. This abnormal inversion effect for faces was observed in a large subset of individual patients with AD. These results suggest that AD patients have deficits in higher-level visual processes, more specifically at perceiving individual faces, a function that relies on holistic representations specific to upright face stimuli. These deficits, combined with their memory impairment, may contribute to the difficulties in recognizing familiar people that are often reported in patients suffering from the disease and by their caregivers.

Memory for public events in mild cognitive impairment and Alzheimer’s disease : the importance of rehearsal

Ribot’s law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer’s disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960–1975; 1976–1990; 1991–2005; 2006–2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models.

Delirium in early-stage Alzheimer's disease : enhancing cognitive reserve as a possible preventive measure

Delirium is a disorder of acute onset with fluctuating symptoms and is characterized by inattention, disorganized thinking, and altered levels of consciousness. The risk for delirium is greatest in individuals with dementia, and the incidence of both is increasing worldwide because of the aging of our population. Although several clinical trials have tested interventions for delirium prevention in individuals without dementia, little is known about the mechanisms for the prevention of delirium in early-stage Alzheimer’s disease (AD). The purpose of this article is to explore ways of preventing delirium and slowing the rate of cognitive decline in early-stage AD by enhancing cognitive reserve. An agenda for future research on interventions to prevent delirium in individuals with early-stage AD is also presented.

Morphologic and genomic characterisation of the koala Chlamydia pneumoniae strain

Chlamydia pneumoniae is a common human and animal pathogen associated with a wide range of upper and lower respiratory tract infections. In more recent years there has been increasing evidence to suggest a link between C. pneumoniae and chronic diseases in humans, including atherosclerosis, stroke and Alzheimer’s disease. C. pneumoniae human strains show little genetic variation, indicating that the human-derived strain originated from a common ancestor in the recent past. Despite extensive information on the genetics and morphology processes of the human strain, knowledge concerning many other hosts (including marsupials, amphibians, reptiles and equines) remains virtually unexplored. The koala (Phascolarctos cinereus) is a native Australian marsupial under threat due to habitat loss, predation and disease. Koalas are very susceptible to chlamydial infections, most commonly affecting the conjunctiva, urogenital tract and/or respiratory tract. To address this gap in the literature, the present study (i) provides a detailed description of the morphologic and genomic architecture of the C. pneumoniae koala (and human) strain, and shows that the koala strain is microscopically, developmentally and genetically distinct from the C. pneumoniae human strain, and (ii) examines the genetic relationship of geographically diverse C. pneumoniae isolates from human, marsupial, amphibian, reptilian and equine hosts, and identifies two distinct lineages that have arisen from animal-to-human cross species transmissions. Chapter One of this thesis explores the scientific problem and aims of this study, while Chapter Two provides a detailed literature review of the background in this field of work. Chapter Three, the first results chapter, describes the morphology and developmental stages of C. pneumoniae koala isolate LPCoLN, as revealed by fluorescence and transmission electron microscopy. The profile of this isolate, when cultured in HEp-2 human epithelial cells, was quite different to the human AR39 isolate. Koala LPCoLN inclusions were larger; the elementary bodies did not have the characteristic pear-shaped appearance, and the developmental cycle was completed within a shorter period of time (as confirmed by quantitative real-time PCR). These in vitro findings might reflect biological differences between koala LPCoLN and human AR39 in vivo. Chapter Four describes the complete genome sequence of the koala respiratory pathogen, C. pneumoniae LPCoLN. This is the first animal isolate of C. pneumoniae to be fully-sequenced. The genome sequence provides new insights into genomic ‘plasticity’ (organisation), evolution and biology of koala LPCoLN, relative to four complete C. pneumoniae human genomes (AR39, CWL029, J138 and TW183). Koala LPCoLN contains a plasmid that is not shared with any of the human isolates, there is evidence of gene loss in nucleotide salvage pathways, and there are 10 hot spot genomic regions of variation that were previously not identified in the C. pneumoniae human genomes. Sequence (partial-length) from a second, independent, wild koala isolate (EBB) at several gene loci confirmed that the koala LPCoLN isolate was representative of a koala C. pneumoniae strain. The combined sequence data provides evidence that the C. pneumoniae animal (koala LPCoLN) genome is ancestral to the C. pneumoniae human genomes and that human infections may have originated from zoonotic infections. Chapter Five examines key genome components of the five C. pneumoniae genomes in more detail. This analysis reveals genomic features that are shared by and/or contribute to the broad ecological adaptability and evolution of C. pneumoniae. This analysis resulted in the identification of 65 gene sequences for further analysis of intraspecific variation, and revealed some interesting differences, including fragmentation, truncation and gene decay (loss of redundant ancestral traits). This study provides valuable insights into metabolic diversity, adaptation and evolution of C. pneumoniae. Chapter Six utilises a subset of 23 target genes identified from the previous genomic comparisons and makes a significant contribution to our understanding of genetic variability among C. pneumoniae human (11) and animal (6 amphibian, 5 reptilian, 1 equine and 7 marsupial hosts) isolates. It has been shown that the animal isolates are genetically diverse, unlike the human isolates that are virtually clonal. More convincing evidence that C. pneumoniae originated in animals and recently (in the last few hundred thousand years) crossed host species to infect humans is provided in this study. It is proposed that two animal-to-human cross species events have occurred in the context of the results, one evident by the nearly clonal human genotype circulating in the world today, and the other by a more animal-like genotype apparent in Indigenous Australians. Taken together, these data indicate that the C. pneumoniae koala LPCoLN isolate has morphologic and genomic characteristics that are distinct from the human isolates. These differences may affect the survival and activity of the C. pneumoniae koala pathogen in its natural host, in vivo. This study, by utilising the genetic diversity of C. pneumoniae, identified new genetic markers for distinguishing human and animal isolates. However, not all C. pneumoniae isolates were genetically diverse; in fact, several isolates were highly conserved, if not identical in sequence (i.e. Australian marsupials) emphasising that at some stage in the evolution of this pathogen, there has been an adaptation/s to a particular host, providing some stability in the genome. The outcomes of this study by experimental and bioinformatic approaches have significantly enhanced our knowledge of the biology of this pathogen and will advance opportunities for the investigation of novel vaccine targets, antimicrobial therapy, or blocking of pathogenic pathways.

Comparison of U.S., Canadian, and Australian participants' performance on the Algase Wandering Scale-Version 2 (AWS-V2)

Background Wandering represents a major problem in the management of patients with Alzheimer’s disease (AD). In this study we examined the utility of the Algase Wandering Scale (AWS), a newly developed psychometric instrument that asks caregivers to assess the likelihood of wandering behavior. Methods The AWS was administered to the caregivers of 40 AD patients and total and subscale scores were examined in relation to measures of mental and functional status, depressive symptoms and medication usage. Results AWS scores were comparable, though slightly lower, than those normative values previously published. Higher scores were associated with more severe dementia. The Negative Outcome subscale showed a significant increase in reported falls or injuries in association with anti-depressant use. Conclusions These data provide some construct validation for the AWS as a potentially useful scale to assess wandering behaviors in AD.

Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.

Muro de las Lagrimas (wall of tears): Living with dementia; family experience of loss and grief

This brief paper will introduce a new theoretical framework or model which may be useful for putting a structure around the theme of ageing and its accompanying grief and loss. It is especially appropriate in the context of counselling families living with dementia, including those individuals with a diagnosis of alzheimers disease. The paper describes the origin of the Spanish expressions of the `wall of tears’ and `house of tears’ and involves an historical narrative of the first author as context to the framework.

Time-varying bispectral analysis of auditory evoked multi-channel scalp EEG

Time-varying bispectra, computed using a classical sliding window short-time Fourier approach, are analyzed for scalp EEG potentials evoked by an auditory stimulus and new observations are presented. A single, short duration tone is presented from the left or the right, direction unknown to the test subject. The subject responds by moving the eyes to the direction of the sound. EEG epochs sampled at 200 Hz for repeated trials are processed between -70 ms and +1200 ms with reference to the stimulus. It is observed that for an ensemble of correctly recognized cases, the best matching timevarying bispectra at (8 Hz, 8Hz) are for PZ-FZ channels and this is also largely the case for grand averages but not for power spectra at 8 Hz. Out of 11 subjects, the only exception for time-varying bispectral match was a subject with family history of Alzheimer’s disease and the difference was in bicoherence, not biphase.

Neurological drugs and opioids for pain management

20.1 Epilepsy and an introduction to drugs used to treat 20.1.1 Introduction to epilepsy 20.1.2 Treatment of partial seizures 20.1.3 Treatment of generalised seizures 20.1.4 Treatment of status epilepticus 20.2 Neurodegenerative disorders; principles of treatment 20.2.1 Introduction to neurodegenerative disorders 20.2.2 Parkinson’s disease 20.2.2.1 Introduction to Parkinson’s disease 20.2.2.2 Dopaminergic system 20.2.2.3 Treatment to enhance the dopaminergic system 20.2.2.4 Treatment to inhibit the cholinergic system 20.2.3 Dementia/Alzheimer’s disease 20.2.3.1 Introduction to Alzheimer’s disease 20.2.3.2 Treatment of Alzheimer’s disease 20.2.4 Amyotrophic lateral sclerosis 43.4.1 Introduction 43.4.2 Treatment 20.3. Pain and opioid analgesics 20.3.1 Introduction to pain and analgesia 20.3.2 Introduction to opioids 20.3.3 Tolerance and physical dependence 20.3.4 Effects of opioids 20.3.5 Agonists at opioid μ receptors 20.3.6 Toxicity to opioids This section deals with the neurologic drugs. The neurologic drugs are used to treat epilepsy and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. The opioids for pain management are also discussed in this section.

Exploring the effect of companion robots on emotional expression in older people with dementia : a pilot randomized controlled trial

This pilot study aimed to compare the effect of companion robots (PARO) to participation in an interactive reading group on emotions in people living with moderate to severe dementia in a residential care setting. A randomized crossover design, with PARO and reading control groups, was used. Eighteen residents with mid- to late-stage dementia from one aged care facility in Queensland, Australia, were recruited. Participants were assessed three times using the Quality of Life in Alzheimer’s Disease, Rating Anxiety in Dementia, Apathy Evaluation, Geriatric Depression, and Revised Algase Wandering Scales. PARO had a moderate to large positive influence on participants’ quality of life compared to the reading group. The PARO intervention group had higher pleasure scores when compared to the reading group. Findings suggest PARO may be useful as a treatment option for people with dementia; however, the need for a larger trial was identified.

Protein markers for Alzheimer disease in the frontal cortex and cerebellum

Objective: To compare proteins related to Alzheimer disease ( AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD ( LOAD) and nondemented control subjects. Methods: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain. Results: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta(40) and Abeta(42) ( by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged. Conclusions: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance.

Current dementia research in Australia : a report from the Alzheimer's Australia 15th National Conference

The Alzheimer’s Australia 15th National Conference held on 14–17 May 2013 in Hobart (Tasmania, Australia) attracted a wide range of attendees, including people living with dementia, family caregivers, health professionals and researchers. The conference theme, The Tiles of Life Coloring the Future, invoking a vision of a better future for those affected by dementia, had seven subthemes: liberation, rehabilitation, leisure,service, creativity, wellbeing and research.