Permanent Memory Loss Research Articles

Heparan sulfate proteoglycans in pathological protein aggregation and brain functionality

Proteoglycans are highly specialized proteins with specific interactive modules in their core proteins, allowing them to engage with a diverse range of cellular and structural proteins, contributing to many varied roles in cell processes. This review examines the roles of heparan sulfate (HS) proteoglycans (HSPGs) in the assembly of pathological protein aggregates in brain tissues, which negatively impact cognitive brain function. While HSPGs play roles in normal brain development, they also contribute to the abnormal accumulation and persistence of protein aggregates in Alzheimer’s and Parkinson’s diseases (AD and PD), prolonging their neurotoxic effects. HSPG-mediated effects on the innate immune system may also contribute to the development of neuroinflammation and pathogenesis of neurodegenerative changes in the central nervous system. These pathological developments lead to impaired cognition, permanent memory loss in dementia and AD, and an inability of the brain to exert normal neuromuscular control, affecting motor functions and body movement in PD. A deeper understanding of the properties of HS in these degenerative processes is essential for the development of therapeutic measures to treat these conditions. Significant improvements in neuroimaging, next-generation glycosaminoglycan analytical techniques, and functional glycomics hold great promise for elucidating the complexities of HS structure and function. These advancements may significantly aid in the development of HS biotherapeutics to treat these debilitating conditions, which are increasingly impacting the aging global population. While a number of promising therapeutic candidates have already emerged, further research is required to optimize their biotherapeutic applications in this challenging area of pathobiology, bioregulation, and the recovery of neural function.

Ensemble Transfer Learning for Distinguishing Cognitively Normal and Mild Cognitive Impairment Patients Using MRI

Alzheimer’s disease is a chronic neurodegenerative disease that causes brain cells to degenerate, resulting in decreased physical and mental abilities and, in severe cases, permanent memory loss. It is considered as the most common and fatal form of dementia. Although mild cognitive impairment (MCI) precedes Alzheimer’s disease (AD), it does not necessarily show the obvious symptoms of AD. As a result, it becomes challenging to distinguish between mild cognitive impairment and cognitively normal. In this paper, we propose an ensemble of deep learners based on convolutional neural networks for the early diagnosis of Alzheimer’s disease. The proposed approach utilises simple averaging ensemble and weighted averaging ensemble methods. The ensemble-based transfer learning model demonstrates enhanced generalization and performance for AD diagnosis compared to traditional transfer learning methods. Extensive experiments on the OASIS-3 dataset validate the effectiveness of the proposed model, showcasing its superiority over state-of-the-art transfer learning approaches in terms of accuracy, robustness, and efficiency.

Detection of Alzheimer’s disease in MRI images using different transfer learning models and improving the classification accuracy

Alzheimer's disease (AD) is a neurodegenerative illness that damages brain cells and impairs a patient's memory over time. If detected early so, the patient can avoid permanent memory loss and further damage to their brain cells. Various automated technologies and techniques have been developed in recent years for the detection of Alzheimer's disease (AD). Methods that focus on rapid, accurate, and early identification of the condition in order to reduce the negative impact on a patient's mental health are available. Medical imaging systems for Alzheimer’s disease (AD) diagnostic performance have been greatly improved by machine learning models. There is a major difficulty with multi-class classification, however, which is the presence of brain structural characteristics that are extremely closely associated. It is possible to improve deep learning by increasing the number of layers and including features and classifiers at all levels of the classification hierarchy. Nevertheless, the vast majority of deep learning models (like traditional CNN model) fail to deliver acceptable results in real-world situations.

A response to yet another defence of ECT in the absence of robust efficacy and safety evidence.

It is estimated that electroconvulsive therapy is still administered to approximately a million people a year. It involves passing enough electric current through the human brain, eight to twelve times, to cause convulsions, in the hope of somehow alleviating emotional suffering, primarily depression. There have only ever been 11 placebo-controlled studies (where general anaesthesia is administered but the electric shock is withheld), all of which were pre-1986, had very small sample sizes and were seriously methodologically flawed. Five of these studies found no difference between the two groups at the end of treatment, four found ECT produced better outcomes for some patients, and two produced mixed results, including one where psychiatrists' ratings produced a difference, but the ratings of nurses and patients did not. In the 80 years since the first ECT no studies have found any evidence that ECT is better than placebo beyond the end of treatment. Nevertheless, all five meta-analyses relying on these studies have somehow concluded that ECT is more effective than placebo despite the studies' multiple failings. Meanwhile, evidence of persistent or permanent memory loss in 12% to 55% of patients has accumulated. Attempts to highlight this failure of ECT proponents to provide robust evidence that their treatment is effective and safe are routinely dismissed, diminished, denied and denounced. This paper responds to one such attempt, by Drs Meechan, Laws, Young, McLoughlin and Jauhar, to discredit two systematic reviews of the eleven pre-1986 studies, in 2010 and 2019, the latter of which also reviewed five meta-analyses that had ignored the studies' failings. The criticisms and claims of the recent crtiique of the two systematic reviews are examined in detail, by the first author of both reviews, for accuracy, relevance and logic. The critique is found to include multiple errors, misrepresentations, omissions, inconsistencies and logical flaws. It is concluded that Meechan et al. fail to make a fact-based, coherent argument against suspending ECT pending a series of large, carefully designed placebo-controlled studies to establish whether ECT does have any beneficial effects against which to weigh the significant established adverse effects.

Evaluating whether EEG could predict Alzheimer's disease onset in preclinical patients with the ApoE4 allele

AbstractBackgroundAlzheimer’s disease (AD) is progressive neurodegenerative disease and is the most common cause of dementia in the elderly. Currently, patients are diagnosed based on memory loss through mental status exams, supportive imaging, and/or laboratory tests. Even though there are no biomarkers or tests available for preclinical patients, the Apolipoprotein E (ApoE) polymorphic alleles indicate if a patient is at high (e4 allele), neutral (e3 allele), or low risk (e2 allele). In this study, we use electroencephalogram (EEG) analysis in preclinical participants at high genetic risk for AD to determine if there are characteristic EEG changes and/or patterns that may predict progression to AD at the preclinical stage.MethodParticipants ages 64 to 78 were selected from Hawaii Pacific Neuroscience’s patient database. Selected participants had a Mini‐Mental Status Exam score of no lower than 28. Participants were asymptomatic at the time of the study. Each participant also had a genotype study to determine their ApoE genotype (11 participants were e3e3; 3 participants were e3e4; 2 participants were e4e4; 1 participant was e2e4). An EEG was conducted to determine any apparent trends via visual analysis.ResultOf the 18 participants who had received EEGs, 6 (33%) displayed evidence of abnormal focal temporal slowing of some kind. 4 of the 6 (e3e3, e3e3, e3e4, e3e4) displayed focal left temporal slowing, and 2 of the 6 displayed bilateral temporal slowing (e4e4, e3e3), of which one was independent (e4e4). The remaining 12 patients did not display any abnormalities in their EEG study. Of the 11 e3e3 genotype participants, 3 (27%) displayed abnormal slowing. Of the 3 e3e4 genotype participants, 2 (67%) displayed abnormal slowing. Of the 2 e4e4 genotype participants, 1 (50%) displayed abnormal slowing.ConclusionThis study suggests that EEGs may be a potential predictive test for the onset of AD in high‐risk patients, particularly with the ApoE4 allele. Future studies may follow the progression of EEGs in this patient population to determine if our EEG data correlates with future onset of cognitive symptoms. If proven to be successful, EEGs may be an additional, noninvasive tool to detect possible AD before progression to permanent memory loss.

A PROPOSED RECOGNITION SYSTEM FOR ALZHEIMER’S DISEASE BASED ON DEEP LEARNING AND OPTIMIZATION ALGORITHMS

Alzheimer's disease (AD) is an advanced and incurable neurodegenerative disease that causes progressive impairment of memory and cognitive functions due to the deterioration of brain cells. Early diagnosis is substantial to avoid permanent memory loss and develop treatments that will be subtracted in the future. Deep learning (DL) is a vital technique for medical imaging systems for AD diagnostics. The problem is multi-class classification seeking high accuracy. DL models have shown strong performance accuracy for multi-class prediction. In this paper, a proposed DL architecture is created to classify magnetic resonance imaging (MRI) to predict different stages of AD-based pre-trained Convolutional Neural Network (CNN) models and optimization algorithms. The proposed model architecture attempts to find the optimal subset of features to improve classification accuracy and reduce classification time. The pre-trained DL models, ResNet-101 and DenseNet-201, are utilized to extract features based on the last layer, and the Rival Genetic algorithm (RGA) and Pbest-Guide Binary Particle Swarm Optimization (PBPSO) are applied to select the optimal features. Then, the DL features and selected features are passed separately through created classifier for classification. The results are compared and analyzed by accuracy, performance metrics, and execution time. Experimental results showed that the most efficient accuracies were obtained by PBPSO selected features which reached 87.3% and 94.8% accuracy with less time of 46.7 sec, 32.7 sec for features based ResNet-101 and DenseNet-201, receptively.

Electroconvulsive therapy (ECT) versus sham ECT for depression: do study limitations invalidate the evidence (and mean we should stop using ECT)?

SUMMARYElectroconvulsive therapy (ECT) for depression is a controversial treatment with highly polarised views about the balance between therapeutic benefits and adverse effects. Studies investigating whether ECT is more effective than a placebo treatment started in the 1950s, with the most important randomised controlled trials carried out about four decades ago in which ECT was compared with sham ECT (SECT) involving anaesthesia but no electrically induced seizure. Subsequently the data have been pooled in a number of meta-analyses which have found that ECT is an effective treatment. However, a recent review of the quality of the SECT-controlled studies, and the meta-analyses based on them, concludes that their quality is too poor to allow assessment of the efficacy of ECT and that, given its risks (permanent memory loss and death), the use of ECT should be suspended. This commentary critically discusses the methodology of this review and its conclusions.

Electroconvulsive Therapy for Depression: A Review of the Quality of ECT versus Sham ECT Trials and Meta-Analyses

BackgroundElectroconvulsive therapy (ECT) is still being administered to approximately a million people annually. There have been no ECT versus simulated ECT (SECT) studies since 1985. The five meta-analyses of ECT versus SECT studies all claim that ECT is more effective than SECT for its primary target, severe depression. This review assesses the quality of those meta-analyses and of the 11 studies on which they are based.MethodsThe meta-analyses were evaluated primarily in terms of whether they considered the quality of the studies they included, but also in terms of whether they addressed efficacy beyond end of treatment. The methodological rigor of the 11 studies included by one or more of the meta-analyses was assessed using a 24-point Quality scale developed for this review.ResultsThe five meta-analyses include between 1 and 7 of the 11 studies. The meta-analyses pay little or no attention to the multiple limitations of the studies they include. The 11 studies have a mean Quality score of 12.3 out of 24. Eight scored 13 or less. Only four studies describe their processes of randomization and testing the blinding. None convincingly demonstrate that they are double-blind. Five selectively report their findings. Only four report any ratings by patients. None assess Quality of Life. The studies are small, involving an average of 37 people. Four of the 11 found ECT significantly superior to SECT at the end of treatment, five found no significant difference and two found mixed results (including one where the psychiatrists reported a difference but patients did not). Only two higher Quality studies report follow-up data, one produced a near-zero effect size (.065) in the direction of ECT, and the other a small effect size (.299) in favor of SECT.ConclusionsThe quality of most SECT–ECT studies is so poor that the meta-analyses were wrong to conclude anything about efficacy, either during or beyond the treatment period. There is no evidence that ECT is effective for its target demographic—older women, or its target diagnostic group—severely depressed people, or for suicidal people, people who have unsuccessfully tried other treatments first, involuntary patients, or children and adolescents. Given the high risk of permanent memory loss and the small mortality risk, this longstanding failure to determine whether or not ECT works means that its use should be immediately suspended until a series of well designed, randomized, placebo-controlled studies have investigated whether there really are any significant benefits against which the proven significant risks can be weighed.

Tension- and Adhesion-Regulated Retraction of Injured Axons

Damage-induced retraction of axons during traumatic brain injury is believed to play a key role in the disintegration of the neural network and to eventually lead to severe symptoms such as permanent memory loss and emotional disturbances. However, fundamental questions such as how axon retraction progresses and what physical factors govern this process still remain unclear. Here, we report a combined experimental and modeling study to address these questions. Specifically, a sharp atomic force microscope probe was used to transect axons and trigger their retraction in a precisely controlled manner. Interestingly, we showed that the retracting motion of a well-developed axon can be arrested by strong cell-substrate attachment. However, axon retraction was found to be retriggered if a second transection was conducted, albeit with a lower shrinking amplitude. Furthermore, disruption of the actin cytoskeleton or cell-substrate adhesion significantly altered the retracting dynamics of injured axons. Finally, a mathematical model was developed to explain the observed injury response of neural cells in which the retracting motion was assumed to be driven by the pre-tension in the axon and progress against neuron-substrate adhesion as well as the viscous resistance of the cell. Using realistic parameters, model predictions were found to be in good agreement with our observations under a variety of experimental conditions. By revealing the essential physics behind traumatic axon retraction, findings here could provide insights on the development of treatment strategies for axonal injury as well as its possible interplay with other neurodegenerative diseases.

Taking Regular Breaks From Sitting Prevents Reductions in Brain Blood Flow

Supplying the brain with enough blood flow is essential to keep us alive and maintain our brain health. Reductions in brain blood flow can negatively affect the ability to think. Decreased blood flow to the brain can also lead to brain diseases, such as dementia, which is a condition that causes permanent memory loss and confusion. Scientists are beginning to think that sitting may be bad for brain blood flow. Understanding how sitting affects the brain is therefore very important. We conducted a study in which participants either sat down without any breaks for 4 h, or sat down but took a short walking break every 30 min, or took a longer walking break every 2 h. After sitting without any breaks, brain blood flow decreased. However, when participants took a walking break every 30 min that prevented the decrease in brain blood flow. These results suggest we should encourage people to take regular breaks from sitting to help maintain brain health.

Chronic low-level exposure to the common seafood toxin domoic acid causes cognitive deficits in mice

The consumption of one meal of seafood containing domoic acid (DA) at levels high enough to induce seizures can cause gross histopathological lesions in hippocampal regions of the brain and permanent memory loss in humans and marine mammals. Seafood regulatory limits have been set at 20mgDA/kg shellfish to protect human consumers from symptomatic acute exposure, but the effects of repetitive low-level asymptomatic exposure remain a critical knowledge gap. Recreational and Tribal-subsistence shellfish harvesters are known to regularly consume low levels of DA. The aim of this study was to determine if chronic low-level DA exposure, at doses below those that cause overt signs of neurotoxicity, has quantifiable impacts on cognitive function. To this end, female C57BL/6NJ mice were exposed to asymptomatic doses of DA (≈0.75mg/kg) or vehicle once a week for several months. Spatial learning and memory were tested in a radial water maze paradigm at one, six and 25 weeks of exposure, after a nine-week recovery period following cessation of exposure, and at three old age time points (18, 24 and 28 months old). Mice from select time points were also tested for activity levels in a novel cage environment using a photobeam activity system. Chronic low-level DA exposure caused significant spatial learning impairment and hyperactivity after 25 weeks of exposure in the absence of visible histopathological lesions in hippocampal regions of the brain. These cognitive effects were reversible after a nine-week recovery period with no toxin exposure and recovery was sustained into old age. These findings identify a new potential health risk of chronic low-level exposure in a mammalian model. Unlike the permanent cognitive impacts of acute exposure, the chronic low-level effects observed in this study were reversible suggesting that these deficits could potentially be managed through cessation of exposure if they also occur in human seafood consumers.

Maternal Opioid Addiction Results in Permanent Memory loss of Off-springs: Are We Aware?

Abstract not availableBangladesh Journal of Medical Science Vol.15(3) 2016 p.499-501

Lipid peroxidation and tyrosine nitration in traumatic brain injury: Insights into secondary injury from redox proteomics.

Traumatic brain injury (TBI) is a spontaneous event in which sudden trauma and secondary injury cause brain damage. Symptoms of TBI can range from mild to severe depending on extent of injury. The outcome can span from complete patient recovery to permanent memory loss and neurological decline. Currently, there is no known cure for TBI; however, immediate medical attention after injury is most beneficial for patient recovery. It is a well-established concept that imbalances in the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and native antioxidant mechanisms have been shown to increase oxidative stress. Over the years, proteomics has been used to identify specific biomarkers in diseases such as cancers and neurological disorders such as Alzheimer disease and Parkinson disease. As TBI is a risk factor for a multitude of neurological diseases, biomarkers for this phenomenon are a likely field of study in order to confirm diagnosis. This review highlights the current proteomics studies that investigated excessively nitrated proteins and those altered by lipid peroxidation in TBI. This review also highlights possible diagnostic measures and provides insights for future treatment strategies.

How specialist ECT consultants inform patients about memory loss

Aims and MethodA questionnaire was distributed to consultants with a special interest in electroconvulsive therapy (ECT) at clinics participating in an ECT accreditation process. This aimed to ascertain a consensus of clinical practice regarding informing patients about the treatment and assessment of memory during ECT.ResultsThe response rate was 64%. There is consensus on informing patients about the possibility of permanent memory loss. Memory is assessed before and during an ECT course by clinical interview and Mini-Mental State Examination, but rarely at long-term follow-up.Clinical ImplicationsPatients need to be informed about the possibility of permanent memory loss before consenting to ECT. Clinical teams need to make greater efforts to assess memory, particularly after this treatment.

Novel effects on memory observed following unilateral intracranial administration of okadaic acid, cyclosporin A, FK506 and [MeVal 4]CyA

The involvement of protein phosphatases and peptidyl-prolyl cis/ trans isomerases (PPIases) in memory formation in the chick has previously been investigated using a single-trial learning task. In these studies, inhibitory agents were administered bilaterally directly to a critical area of the chick brain. These studies are now extended to investigate whether similar effects are obtained if the drugs are administered unilaterally. All of the effects reported previously following bilateral administration of okadaic acid (OA), cyclosporin A (CyA), FK506 and [MeVal 4]CyA can be attributed to their action in just one hemisphere. OA, at a concentration known to selectively inhibit PP2A in vitro (0.5 nM) results in permanent memory loss from 30–40 min post-training when injected in the left hemisphere, but has no effect when injected in the right hemisphere. A higher concentration of OA (100 nM), which inhibits both PP2A and PP1 in vitro, has a similar effect in the left hemisphere but causes a transient period of memory loss from 10–20 min post-training when injected in the right hemisphere. CyA (5 nM and 20 nM), which inhibits both PP2B and PPIase activity, causes permanent memory loss from 60 min post-training when injected into the left hemisphere, an effect also observed following administration of FK506 (20 nM), which also inhibits PP2B and PPIase activity, and [MeVal 4]CyA (5 nM), which inhibits PPIase activity but not PP2B activity. Administration of CyA (20 nM) and FK506, but not [MeVal 4]CyA, in the right hemisphere leads to a transient period of memory loss from 10–20 min post-training. These results confirm significant roles for phosphatases and PPIases in memory processing but challenge previous conclusions drawn on the basis of bilateral drug administration protocols.

Fragmentary and en bloc blackouts: similarity and distinction among episodes of alcohol-induced memory loss.

En bloc and fragmentary blackouts are distinguishable forms of alcohol-induced amnesia. The former are instances of full and permanent memory loss for intoxicated events, whereas the latter are episodes for which retrieval of experiences is facilitated by provision of cues. Beyond this nosological difference, little is known about descriptive dimensions of the two blackout types. The current study assessed their characteristics as reported by a group of heavy drinking young adults. A sample of 136 young adult volunteers (54% male; mean [SD] age = 22.71 [2.23]) were administered a Time-Line Follow-Back assessment, expanded to gather descriptive information about the occurrence and characteristics of en bloc and fragmentary blackouts. Although overall reporting of blackouts by the sample mirrored rates reported in prior research, prevalence and incidence of fragmentary blackouts were more than threefold those of en bloc blackouts. A surprising finding was that the two blackout types exhibited a similar range and distribution of corresponding blood alcohol concentrations. Most en bloc blackouts involved concurrent use of illicit substances; polysubstance use was reported for few fragmentary blackouts. In addition, subjective evaluations of en bloc blackouts were quite negative, whereas fragmentary blackouts were evaluated as only mildly negative. Beyond nosological distinctions, en bloc and fragmentary blackouts differ on several descriptive dimensions. The collective findings expand understanding of diversity in experiences that accompany memory loss after drinking.

Electroconvulsive therapy and memory loss: a personal journey.

The cause for the significant gap between research and anecdotal evidence regarding the extent of some memory loss after electroconvulsive therapy (ECT) has never been adequately explained. A patient's development of awareness and self-education about her severe side effects from ECT raises questions regarding many current assumptions about memory loss. ECT-specific studies, which conclude that side effects are short term and narrow in scope, have serious limitations, including the fact that they do not take into account broader scientific knowledge about memory function. Because of the potential for devastating and permanent memory loss with ECT, informed consent needs significant enhancement until advancing research on both improved techniques and on better predictive knowledge regarding memory loss progresses to making a greater impact on clinical applications. Follow-up care and education in coping skills need to be a regular part of ECT practice when patients do experience severe effects.

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is a safe, effective, valuable treatment for serious affective disorders (eg, major depression). Sometimes indicated for other, occasionally nonpsychiatric, medical conditions, ECT is a moderately complex procedure for which training is provided routinely during psychiatric residency. Although temporary confusion and amnesia are expected immediately after treatment, no reliable data suggest that permanent memory loss or cognitive deficit is caused by modern ECT. Indeed, because severe depression itself often causes both memory and cognitive deficits, ECT's remarkable therapeutic effectiveness is associated with long-term improvement in cognition, learning ability, and memory for many patients. Controversy over safety and effect on memory is fueled largely by public misinformation.

Spontaneous recovery in human learning.

The occurrence of spontaneous recovery -of unlearned verbal materials was examined. While previous reviews have questioned whether spontaneous recovery actually occurs in the standard A-B, A-C paired-associate paradigm, the present summary suggests that the evidence does support its existence. The following topics related to spontaneous recovery were considered: (a) effects of variations in conditions of learning (original and interpolated), (b) effects of paradigm variation, (c) theoretical interpretations (conditioning versus response set), (d) empirical alternatives to the concept of recovery, and (e) extensions to single-list designs. Whenever material is processed into memory, there are logically only two things which can happen to the information: either it remains retrievable (remembered) or it is lost (forgotten) due to irretrievabil ity or ultimate disappearance. Both of these options are obvious and require no elaboration. There is, however, another process which may occur, involving the forgetting and subsequent recall of information. Although this area has been less systematically studied, it is of interest in two respects: 1. It is an intuitive puzzle of practical interest. Why should memories which were once lost become available again? More importantly, what steps can be followed to reaccess the material? 2. It is a theoretical puzzle. Specifically, it may enable a better understanding of the processes involved with permanent memory loss. Obviously, one cannot examine the properties of unretrievable information to understand better how it was lost. However, by a systematic examination of the conditions under which memory information can be recovered, perhaps some insight into the nature of the initial loss may be gained. This may be accomplished by looking at (a) the

Dreams of subjects with loss of memory for recent events.

ABSTRACTDreams of six subjects with postencephalitic complete loss of memory for recent events were compared to dreams of control subjects with intact memory. The incidence of dreams decreased with the memory defect. Furthermore, the dreams were shorter, simpler, reality bound, lacked daily residue and emotional depth, and followed secondary‐thought‐type logic. They were stereotyped and repetitious. Instead of symbolically elaborated new attempted solutions for recent conflicts, these dreams contained the memory of events the subjects experienced before the onset of the memory defect. In each instance, the remembered event once offered a relief for a physiological need, similar to the one that precipitated the dream. Assuming that the mechanism of dreaming remains intact in these subjects with permanent memory loss for recent events, the results suggest that dreams of subjects with intact memory combine two processes: 1) a sensory stimulus of internal origin (e.g., an organic need) may serve as a decoding signal resulting in retrieval of an old memory trace; and 2) processes connected with perception and encoding the memory of recent events contribute the daily residue and the newly created symbolic elaboration of the daily residue, and old memory traces under an emotional impact.