The Links between Brain Insulin Resistance and Alzheimer’s Disease

Type 2 Diabetes (T2DM) and Alzheimer's disease (AD) are two main health problems influencing millions of people in the world. Neuron loss and synaptic impairment that interfere with cognition and memory cause for the behavioral indications of AD. While it is now accepted that insulin has central neuromodulatory purpose, it was contemplated for many years that brain is insusceptible to insulin, involving its function in memory and learning, which are impaired in AD. The common characteristics of both AD and T2D are impaired insulin signaling, oxidative stress, the excitation of inflammatory pathways and unqualified glucose metabolism. This review summarizes how the recognition of these mechanisms may lead to the development of alternative therapeutic approaches. Here we summarize how the recognition of these mechanisms may lead to the development of alternative therapeutic approaches.

Prediction Modeling of Alzheimer’s Disease and Its Prodromal Stages from Multimodal Data with Missing Values

A major challenge in medical studies, especially those that are longitudinal, is the problem of missing measurements which hinders the effective application of many machine learning algorithms. Furthermore, recent Alzheimer's Disease studies have focused on the delineation of Early Mild Cognitive Impairment (EMCI) and Late Mild Cognitive Impairment (LMCI) from cognitively normal controls (CN) which is essential for developing effective and early treatment methods. To address the aforementioned challenges, this paper explores the potential of using the eXtreme Gradient Boosting (XGBoost) algorithm in handling missing values in multiclass classification. We seek a generalized classification scheme where all prodromal stages of the disease are considered simultaneously in the classification and decision-making processes. Given the large number of subjects (1631) included in this study and in the presence of almost 28% missing values, we investigated the performance of XGBoost on the classification of the four classes of AD, NC, EMCI, and LMCI. Using 10-fold cross validation technique, XGBoost is shown to outperform other state-of-the-art classification algorithms by 3% in terms of accuracy and F-score. Our model achieved an accuracy of 80.52%, a precision of 80.62% and recall of 80.51%, supporting the more natural and promising multiclass classification.

In vitro and in vivo Assessment of Cholinesterase Inhibitory Activity of the Bark Extracts of Pterocarpus santalinus L. for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.

Early Diagnosis of Alzheimer's Disease Using a Combination of Images Processing and Brain Signals

Alzheimer's prevalence is on the rise, and the disease comes with problems like cessation of treatment, high cost of treatment, and the lack of early detection methods. The pathology of this disease causes the formation of protein deposits in the brain of patients called plaque amyloid. Generally, the diagnosis of this disease is done by performing tests such as a cerebrospinal fluid, CT scan, MRI, and spinal cord fluid testing, or mental testing tests and eye tracing tests. In this paper, we tried to use the Medial Temporal Atrophy (MTA) method and the Leave One Out (LOO) cycle to extract the statistical properties of the three Fz, Pz, and Cz channels of ERP signals for early diagnosis of this disease. In the process of CT scan images, the accuracy of the results is 81% for the healthy person and 88% for the severe patient. After the process of ERP signaling, the accuracy of the results for a healthy person in the delta band in the Cz channel is 81% and in the alpha band the Pz channel is 90%. In the results obtained from the signal processing, the results of the severe patient in the delta band of the Cz channel were 89% and in the alpha band Pz channel 92%.

Language Processing of Seniors with Alzheimer’s Disease: From the Perspective of Temporal Parameters

The present paper aims to examine the language processing of Chinese-speaking seniors with Alzheimer’s disease (AD) from the perspective of temporal cues. Twenty healthy adults, 17 healthy seniors, and 13 seniors with AD in Taiwan participated in this study to tell stories based on two sets of pictures. Nine temporal cues were fetched and analyzed. Oral productions in Mandarin Chinese were compared and discussed to examine to what extent and in what way these three groups of participants performed with significant differences. Results indicated that the age effects were significant in filled pauses. The dementia effects were significant in mean duration of pauses, empty pauses, filled pauses, lexical pauses, normalized mean duration of filled pauses and lexical pauses. The findings reported in the current paper help characterize the nature of language processing in seniors with or without AD, and contribute to the interactions between the AD neural mechanism and their temporal parameters.

Clustering-Based Detection of Alzheimer's Disease Using Brain MR Images

This paper presents a comprehensive survey of recent research studies to segment and classify brain MR (magnetic resonance) images in order to detect significant changes to brain ventricles. The paper also presents a general framework for detecting regions that atrophy, which can help neurologists in detecting and staging Alzheimer. Furthermore, a prototype was implemented to segment brain MR images in order to extract the region of interest (ROI) and then, a classifier was employed to differentiate between normal and abnormal brain tissues. Experimental results show that the proposed scheme can provide a reliable second opinion that neurologists can benefit from.

ATR-IR Study of the Mechanism of Aluminum Chloride Induced Alzheimer’s Disease; Curative and Protective Effect of Lipidium sativum Water Extract on Hippocampus Rats Brain Tissue

The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width (HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder, and decreasing in lipid polarity in AlCl3 group indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approached nearly the control values. These results supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. In addition, the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Diagnostic Contribution of the MMSE-2:EV in the Detection and Monitoring of the Cognitive Impairment: Case Studies

The goal of this paper is to present the diagnostic contribution that the screening instrument, Mini-Mental State Examination-2: Expanded Version (MMSE-2:EV), brings in detecting the cognitive impairment or in monitoring the progress of degenerative disorders. The diagnostic signification is underlined by the interpretation of the MMSE-2:EV scores, resulted from the test application to patients with mild and major neurocognitive disorders. The cases were selected from current practice, in order to cover vast and significant neurocognitive pathology: mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed dementia, Parkinson’s disease, conversion of the mild cognitive impairment into Alzheimer’s disease. The MMSE-2:EV version was used: it was applied one month after the initial assessment, three months after the first reevaluation and then every six months, alternating the blue and red forms. Correlated with age and educational level, the raw scores were converted in T scores and then, with the mean and the standard deviation, the z scores were calculated. The differences of raw scores between the evaluations were analyzed from the point of view of statistic signification, in order to establish the progression in time of the disease. The results indicated that the psycho-diagnostic approach for the evaluation of the cognitive impairment with MMSE-2:EV is safe and the application interval is optimal. In clinical settings with a large flux of patients, the application of the MMSE-2:EV is a safe and fast psychodiagnostic solution. The clinicians can draw objective decisions and for the patients: it does not take too much time and energy, it does not bother them and it doesn’t force them to travel frequently.

Antioxidative, Anticholinesterase and Anti-Neuroinflammatory Properties of Malaysian Brown and Green Seaweeds

Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several proinflammatory cytokines, nitric oxide (NO) and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anticoagulation, antimicrobial, antioxidative, anticancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. These seaweeds significantly exhibited potent DPPH and moderate superoxide anion radical scavenging ability (P

Altered Network Organization in Mild Alzheimer's Disease Compared to Mild Cognitive Impairment Using Resting-State EEG

Brain functional networks based on resting-state EEG data were compared between patients with mild Alzheimer’s disease (mAD) and matched patients with amnestic subtype of mild cognitive impairment (aMCI). We integrated the time–frequency cross mutual information (TFCMI) method to estimate the EEG functional connectivity between cortical regions and the network analysis based on graph theory to further investigate the alterations of functional networks in mAD compared with aMCI group. We aimed at investigating the changes of network integrity, local clustering, information processing efficiency, and fault tolerance in mAD brain networks for different frequency bands based on several topological properties, including degree, strength, clustering coefficient, shortest path length, and efficiency. Results showed that the disruptions of network integrity and reductions of network efficiency in mAD characterized by lower degree, decreased clustering coefficient, higher shortest path length, and reduced global and local efficiencies in the delta, theta, beta2, and gamma bands were evident. The significant changes in network organization can be used in assisting discrimination of mAD from aMCI in clinical.

Evaluation of Antioxidant Activities of Cabbage (Brassica oleracea L. var. capitata L.)

At present, it is widely-known that free radicals are the causes of illness such as cancers, coronary heart disease, Alzheimer’s disease and aging. One method of protection from free radical is the consumption of antioxidant-containing foods or herbs. Several analytical methods have been used for qualitative and quantitative determination of antioxidants. This project aimed to evaluate antioxidant activity of ethanolic and aqueous extracts from cabbage (Brassicca oleracea L. var. capitata L.) measured by DPPH and Hydroxyl radical scavenging method. The results show that averaged antioxidant activity measured in ethanolic extract (µmol Ascorbic acid equivalent/g fresh mass) were 7.316 ± 0.715 and 4.66 ± 1.029 as determined by DPPH and Hydroxyl radical scavenging activity assays respectively. Averaged antioxidant activity measured in aqueous extract (µmol Ascorbic acid equivalent/g fresh mass) were 15.141 ± 2.092 and 4.955 ± 1.975 as determined by DPPH and Hydroxyl radical scavenging activity assays respectively.

In vitro and in vivo Anticholinesterase Activity of the Volatile Oil of the Aerial Parts of Ocimum basilicum L. and O. africanum Lour. Growing in Egypt

In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. The major constituents of the two oils were isolated using several column chromatographies. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activities of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamineinduced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Automatic Classification of Initial Categories of Alzheimer's Disease from Structural MRI Phase Images: A Comparison of PSVM, KNN and ANN Methods

An early and accurate detection of Alzheimer's disease (AD) is an important stage in the treatment of individuals suffering from AD. We present an approach based on the use of structural magnetic resonance imaging (sMRI) phase images to distinguish between normal controls (NC), mild cognitive impairment (MCI) and AD patients with clinical dementia rating (CDR) of 1. Independent component analysis (ICA) technique is used for extracting useful features which form the inputs to the support vector machines (SVM), K nearest neighbour (kNN) and multilayer artificial neural network (ANN) classifiers to discriminate between the three classes. The obtained results are encouraging in terms of classification accuracy and effectively ascertain the usefulness of phase images for the classification of different stages of Alzheimer-s disease.

Voice Disorders Identification Using Hybrid Approach: Wavelet Analysis and Multilayer Neural Networks

This paper presents a new strategy of identification and classification of pathological voices using the hybrid method based on wavelet transform and neural networks. After speech acquisition from a patient, the speech signal is analysed in order to extract the acoustic parameters such as the pitch, the formants, Jitter, and shimmer. Obtained results will be compared to those normal and standard values thanks to a programmable database. Sounds are collected from normal people and patients, and then classified into two different categories. Speech data base is consists of several pathological and normal voices collected from the national hospital “Rabta-Tunis". Speech processing algorithm is conducted in a supervised mode for discrimination of normal and pathology voices and then for classification between neural and vocal pathologies (Parkinson, Alzheimer, laryngeal, dyslexia...). Several simulation results will be presented in function of the disease and will be compared with the clinical diagnosis in order to have an objective evaluation of the developed tool.

Automated Detection of Alzheimer Disease Using Region Growing technique and Artificial Neural Network

Alzheimer is known as the loss of mental functions such as thinking, memory, and reasoning that is severe enough to interfere with a person's daily functioning. The appearance of Alzheimer Disease symptoms (AD) are resulted based on which part of the brain has a variety of infection or damage. In this case, the MRI is the best biomedical instrumentation can be ever used to discover the AD existence. Therefore, this paper proposed a fusion method to distinguish between the normal and (AD) MRIs. In this combined method around 27 MRIs collected from Jordanian Hospitals are analyzed based on the use of Low pass -morphological filters to get the extracted statistical outputs through intensity histogram to be employed by the descriptive box plot. Also, the artificial neural network (ANN) is applied to test the performance of this approach. Finally, the obtained result of t-test with confidence accuracy (95%) has compared with classification accuracy of ANN (100 %). The robust of the developed method can be considered effectively to diagnose and determine the type of AD image.

Mirror Neuron System Study on Elderly Using Dynamic Causal Modeling fMRI Analysis

Dynamic Causal Modeling (DCM) functional Magnetic Resonance Imaging (fMRI) is a promising technique to study the connectivity among brain regions and effects of stimuli through modeling neuronal interactions from time-series neuroimaging. The aim of this study is to study characteristics of a mirror neuron system (MNS) in elderly group (age: 60-70 years old). Twenty volunteers were MRI scanned with visual stimuli to study a functional brain network. DCM was employed to determine the mechanism of mirror neuron effects. The results revealed major activated areas including precentral gyrus, inferior parietal lobule, inferior occipital gyrus, and supplementary motor area. When visual stimuli were presented, the feed-forward connectivity from visual area to conjunction area was increased and forwarded to motor area. Moreover, the connectivity from the conjunction areas to premotor area was also increased. Such findings can be useful for future diagnostic process for elderly with diseases such as Parkinson-s and Alzheimer-s.

Study of EEGs from Somatosensory Cortex and Alzheimer's Disease Sources

This study is to investigate the electroencephalogram (EEG) differences generated from a normal and Alzheimer-s disease (AD) sources. We also investigate the effects of brain tissue distortions due to AD on EEG. We develop a realistic head model from T1 weighted magnetic resonance imaging (MRI) using finite element method (FEM) for normal source (somatosensory cortex (SC) in parietal lobe) and AD sources (right amygdala (RA) and left amygdala (LA) in medial temporal lobe). Then, we compare the AD sourced EEGs to the SC sourced EEG for studying the nature of potential changes due to sources and 5% to 20% brain tissue distortions. We find an average of 0.15 magnification errors produced by AD sourced EEGs. Different brain tissue distortion models also generate the maximum 0.07 magnification. EEGs obtained from AD sources and different brain tissue distortion levels vary scalp potentials from normal source, and the electrodes residing in parietal and temporal lobes are more sensitive than other electrodes for AD sourced EEG.