Detection Of Alzheimer's Disease Research Articles

Alzheimer's disease: from early pathogenesis to novel therapeutic approaches.

The mainstay behind Alzheimer's disease (AD) remains unknown due to the elusive pathophysiology of the disease. Beta-amyloid and phosphorylated Tau is still widely incorporated in various research studies while studying AD. However, they are not sufficient. Therefore, many scientists and researchers have dug into AD studies to deliver many innovations in this field. Many novel biomarkers, such as phosphoglycerate-dehydrogenase, clusterin, microRNA, and a new peptide ratio (Aβ37/Aβ42) in cerebral-spinal fluid, plasma glial-fibrillary-acidic-protein, and lipid peroxidation biomarkers, are mushrooming. They are helping scientists find breakthroughs and substantiating their research on the early detection of AD. Neurovascular unit dysfunction in AD is a significant discovery that can help us understand the relationship between neuronal activity and cerebral blood flow. These new biomarkers are promising and can take these AD studies to another level. There have also been big steps forward in diagnosing and finding AD. One example is self-administered-gerocognitive-examination, which is less expensive and better at finding AD early on than mini-mental-state-examination. Quantum brain sensors and electrochemical biosensors are innovations in the detection field that must be explored and incorporated into the studies. Finally, novel innovations in AD studies like nanotheranostics are the future of AD treatment, which can not only diagnose and detect AD but also offer treatment. Non-pharmacological strategies to treat AD have also yielded interesting results. Our literature review spans from 1957 to 2022, capturing research and trends in the field over six decades. This review article is an update not only on the recent advances in the search for credible biomarkers but also on the newer detection techniques and therapeutic approaches targeting AD.

The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are severe age-related disorders with complex and multifactorial causes. Recent research suggests a critical link between neurodegeneration and the gut microbiome, via the gut–brain communication pathway. This review examines the role of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, in the development of AD and PD, and investigates its interaction with microRNAs (miRNAs) along this bidirectional pathway. TMAO, which is produced from dietary metabolites like choline and carnitine, has been linked to increased neuroinflammation, protein misfolding, and cognitive decline. In AD, elevated TMAO levels are associated with amyloid-beta and tau pathologies, blood–brain barrier disruption, and neuronal death. TMAO can cross the blood–brain barrier and promote the aggregation of amyloid and tau proteins. Similarly, TMAO affects alpha-synuclein conformation and aggregation, a hallmark of PD. TMAO also activates pro-inflammatory pathways such as NF-kB signaling, exacerbating neuroinflammation further. Moreover, TMAO modulates the expression of various miRNAs that are involved in neurodegenerative processes. Thus, the gut microbiome–miRNA–brain axis represents a newly discovered mechanistic link between gut dysbiosis and neurodegeneration. MiRNAs regulate the key pathways involved in neuroinflammation, oxidative stress, and neuronal death, contributing to disease progression. As a direct consequence, specific miRNA signatures may serve as potential biomarkers for the early detection and monitoring of AD and PD progression. This review aims to elucidate the complex interrelationships between the gut microbiota, trimethylamine-N-oxide (TMAO), microRNAs (miRNAs), and the central nervous system, and the implications of these connections in neurodegenerative diseases. In this context, an overview of the current neuroradiology techniques available for studying neuroinflammation and of the animal models used to investigate these intricate pathologies will also be provided. In summary, a bulk of evidence supports the concept that modulating the gut–brain communication pathway through dietary changes, the manipulation of the microbiome, and/or miRNA-based therapies may offer novel approaches for implementing the treatment of debilitating neurological disorders.

Could Accelerated Long-Term Forgetting Be a Feature of the Higher Rate of Memory Complaints Associated with Subjective Cognitive Decline? An Exploratory Study.

Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection.

Detection of Alzheimer’s disease using Otsu thresholding with tunicate swarm algorithm and deep belief network

Introduction: Alzheimer’s Disease (AD) is a degenerative brain disorder characterized by cognitive and memory dysfunctions. The early detection of AD is necessary to reduce the mortality rate through slowing down its progression. The prevention and detection of AD is the emerging research topic for many researchers. The structural Magnetic Resonance Imaging (sMRI) is an extensively used imaging technique in detection of AD, because it efficiently reflects the brain variations.Methods: Machine learning and deep learning models are widely applied on sMRI images for AD detection to accelerate the diagnosis process and to assist clinicians for timely treatment. In this article, an effective automated framework is implemented for early detection of AD. At first, the Region of Interest (RoI) is segmented from the acquired sMRI images by employing Otsu thresholding method with Tunicate Swarm Algorithm (TSA). The TSA finds the optimal segmentation threshold value for Otsu thresholding method. Then, the vectors are extracted from the RoI by applying Local Binary Pattern (LBP) and Local Directional Pattern variance (LDPv) descriptors. At last, the extracted vectors are passed to Deep Belief Networks (DBN) for image classification.Results and Discussion: The proposed framework achieves supreme classification accuracy of 99.80% and 99.92% on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarker and Lifestyle flagship work of ageing (AIBL) datasets, which is higher than the conventional detection models.

Detection of Alzheimer's disease using Otsu thresholding with tunicate swarm algorithm and deep belief network.

Introduction: Alzheimer's Disease (AD) is a degenerative brain disorder characterized by cognitive and memory dysfunctions. The early detection of AD is necessary to reduce the mortality rate through slowing down its progression. The prevention and detection of AD is the emerging research topic for many researchers. The structural Magnetic Resonance Imaging (sMRI) is an extensively used imaging technique in detection of AD, because it efficiently reflects the brain variations. Methods: Machine learning and deep learning models are widely applied on sMRI images for AD detection to accelerate the diagnosis process and to assist clinicians for timely treatment. In this article, an effective automated framework is implemented for early detection of AD. At first, the Region of Interest (RoI) is segmented from the acquired sMRI images by employing Otsu thresholding method with Tunicate Swarm Algorithm (TSA). The TSA finds the optimal segmentation threshold value for Otsu thresholding method. Then, the vectors are extracted from the RoI by applying Local Binary Pattern (LBP) and Local Directional Pattern variance (LDPv) descriptors. At last, the extracted vectors are passed to Deep Belief Networks (DBN) for image classification. Results and Discussion: The proposed framework achieves supreme classification accuracy of 99.80% and 99.92% on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarker and Lifestyle flagship work of ageing (AIBL) datasets, which is higher than the conventional detection models.

Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample.

Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD). Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU). In the CU, amyloid-negative (A-) subset, plasma p-tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p-tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A- at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p-tau217 levels predicted faster preclinical cognitive decline. p-tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression. Phosphorylated-tau217 (p-tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age-related trajectories were seen for all the plasma markers in amyloid-negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p-tau217 trajectories. Higher plasma p-tau217 was associated with faster preclinical cognitive decline.

An Implementation of Effective CNN Model for AD Detection

This paper focuses on detecting Alzheimer’s Disease (AD). The most usual form of dementia is Alzheimer's disease, which causes permanent cause memory cell damage. Alzheimer's disease, a neurodegenerative disease, increases slowly over time. For this matter, early detection of Alzheimer's disease is important. The purpose of this work is using Magnetic Resonance Imaging (MRI) to diagnose AD. A Convolution Neural Network (CNN) model, Reset, and VGG the pre-trained learning models are used. Performing analysis and validation of layers affects the effectiveness of the model. T1-weighted MRI images are taken for preprocessing from ADNI. The Dataset images are taken from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 3D MRI scans into 2D image slices shows the optimization method in the training process while achieving 96% and 94% accuracy in VGG 16 and ResNet 18 respectively. This study aims to classify AD from brain 3D MRI images and obtain better results.

Alzheimer’s Disease Detection in MRI images using Deep Convolutional Neural Network Model

Alzheimer's disease (AD) is a neurodegenerative disease that affects cognitive abilities (thinking and memory etc) primarily among the elderly, due to which collective cognitive skills deteriorate, ultimately leading to death. Early detection of Alzheimer's disease is crucial for determining appropriate therapeutic options. This research investigates the use of a Deep Convolutional Neural Network (CNN) for detecting Alzheimer's disease. Due to similar brain patterns and pixel intensities, CNN demonstrates promising results in diagnosing AD through automated feature extraction and characterization. Deep Learning algorithms are designed to perform automated feature extraction and categorization of input image datasets. In this study, a two-way classifier categorizes each image as either Healthy Control (HC) or Alzheimer's disease (AD). Experiments were carried out with the MIRIAD dataset, and the accuracy of disease classification into binary categories was evaluated. The recorded results of CNN with 4- and 5 -layer architectures confirms the effectiveness of the proposed method for AD detection.

Enhancing Alzheimer's disease diagnosis and staging: a multistage CNN framework using MRI.

This study addresses the pervasive and debilitating impact of Alzheimer's disease (AD) on individuals and society, emphasizing the crucial need for timely diagnosis. We present a multistage convolutional neural network (CNN)-based framework for AD detection and sub-classification using brain magnetic resonance imaging (MRI). After preprocessing, a 26-layer CNN model was designed to differentiate between healthy individuals and patients with dementia. After detecting dementia, the 26-layer CNN model was reutilized using the concept of transfer learning to further subclassify dementia into mild, moderate, and severe dementia. Leveraging the frozen weights of the developed CNN on correlated medical images facilitated the transfer learning process for sub-classifying dementia classes. An online AD dataset is used to verify the performance of the proposed multistage CNN-based framework. The proposed approach yielded a noteworthy accuracy of 98.24% in identifying dementia classes, whereas it achieved 99.70% accuracy in dementia subclassification. Another dataset was used to further validate the proposed framework, resulting in 100% performance. Comparative evaluations against pre-trained models and the current literature were also conducted, highlighting the usefulness and superiority of the proposed framework and presenting it as a robust and effective AD detection and subclassification method.

Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer's Disease by Targeting Aβ Oligomers.

Amyloid-β oligomers (AβOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aβ plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AβOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AβOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AβOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AβOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AβOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.

The Role of Non-coding RNAs in Alzheimer's Disease: Pathogenesis, Novel Biomarkers, and Potential Therapeutic Targets.

Long non-coding RNAs (IncRNAs) are regulatory RNA transcripts that have recently been associated with the onset of many neurodegenerative illnesses, including Alzheimer's disease (AD). Several IncRNAs have been found to be associated with AD pathophysiology, each with a distinct mechanism. In this review, we focused on the role of IncRNAs in the pathogenesis of AD and their potential as novel biomarkers and therapeutic targets. Searching for relevant articles was done using the PubMed and Cochrane library databases. Studies had to be published in full text in English in order to be considered. Some IncRNAs were found to be upregulated, while others were downregulated. Dysregulation of IncRNAs expression may contribute to AD pathogenesis. Their effects manifest as the synthesis of beta-amyloid (Aβ) plaques increases, thereby altering neuronal plasticity, inducing inflammation, and promoting apoptosis. Despite the need for more investigations, IncRNAs could potentially increase the sensitivity of early detection of AD. Until now, there has been no effective treatment for AD. Hence, InRNAs are promising molecules and may serve as potential therapeutic targets. Although several dysregulated AD-associated lncRNAs have been discovered, the functional characterization of most lncRNAs is still lacking.

Electrochemical cDNA-sensing of miRNA-137 for detection of Alzheimer's disease using CuO and PEI deposited Au-Pd bimetallic nanoparticles

Alzheimer's disease (AD) is the third most predominantly occurring disease worldwide that is characterized by progressive deterioration of brain cells and change in behaviour, personality, orientation of time and space, leading to functional disability which affects the daily life of patient. We report an electrochemical complementary DNA (cDNA)-sensor for detection of AD by using the blood biomarker, micro-ribonucleic acid-137 (miRNA-137). In this context, the gold-palladium/polyethyleneimine@copperoxide nanocomposite-coated fluorine tin oxide (Au-Pd/PEI@CuO/FTO) electrode is used as an immobilization platform for complementary DNA (cDNA) against the target miRNA-137. The thiolated-cDNA (Thi-cDNA) and Au-Pd bimetallic particles interact through the stable electrostatic binding. The fabricated Au-Pd/PEI@CuO/FTO was characterized by Field emission scanning electron microscopy, Cyclic voltammetry, and Electrochemical Impendence Spectroscopy. The sensor showed response time of 20 minutes with the linear range of 1fM to 100 nM and limit of detection as 0.164 pM. The recovery of the cDNA-sensor for spiked human serum sample ranged from 99.3% to 103.28% with RSD value of 0.62% to 2.81%. The easy-to-use procedure, cost effectiveness, compactness, long shelf life (28 days) and high selectivity of cDNA-sensor towards miRNA-137 over even the one-base pair mismatch recommends the sensor's portability and real-life usability for AD detection.

Deep Learning Approach for Early Detection of Alzheimers Disease

Abstract: Alzheimer’s disease (AD) is a chronic, irreversible brain disorder, no effective cure for it till now. However, available medicines can delay its progress. Therefore, the early detection of AD plays a crucial role in preventing and controlling its progression. The main objective is to design an end-to-end framework for early detection of Alzheimer’s disease and medical image classification for various AD stages. A deep learning approach, specifically convolutional neural networks (CNN), is used in this work. Four stages of the AD spectrum are multi-classified. Furthermore, separate binary medical image classifications are implemented between each two-pair class of AD stages.

Design and synthesis of hemicyanine-based NIRF probe for detecting Aβ aggregates in Alzheimer’s disease

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, has garnered increased attention due to its substantial economic burden and the escalating global aging phenomenon. Amyloid-β deposition is a key pathogenic marker observed in the brains of Alzheimer’s sufferers. Based on real-time, safe, low-cost, and commonly used, near-infrared fluorescence (NIRF) imaging technology have become an essential technique for the detection of AD in recent years. In this work, NIRF probes with hemicyanine structure were designed, synthesized and evaluated for imaging Aβ aggregates in the brain. We use the hemicyanine structure as the parent nucleus to enhance the probe’s optical properties. The introduction of PEG chain is to improve the probe’s brain dynamice properties, and the alkyl chain on the N atom is to enhance the fluorescence intensity of the probe after binding to the Aβ aggregates as much as possible. Among these probes, Z2, Z3, Z6, X3, X6 and T1 showed excellent optical properties and high affinity to Aβ aggregates (Kd = 24.31 ∼ 59.60 nM). In vitro brain section staining and in vivo NIRF imaging demonstrated that X6 exhibited superior discrimination between Tg mice and WT mice, and X6 has the best brain clearance rate. As a result, X6 was identified as the optimal probe. Furthermore, the docking theory calculation results aided in describing X6′s binding behavior with Aβ aggregates. As a high-affinity, high-selectivity, safe and effective probe of targeting Aβ aggregates, X6 is a promising NIRF probe for in vivo detection of Aβ aggregates in the AD brain.

Alzhimer Detection Using CNN

Abstract: Alzheimer's Disease (AD) is a progressive neurodegenerative disease. It is most popular Alzheimer disease symptoms include trouble thinking, making judgment and decision, not able to do familiar task it’s going to also cause alteration in personality and behavior .The factor of AD development is poorly known. As the sickness advances, an individual with Alzheimer disease will develop severe amnesia and lose the capacity to perform everyday activation. This incurable disease is mainly found within elderly people. Neuroimaging technique like MRI and PET scan are used for AD detection. For better result multi model neuroimaging technique are used with DL algorithm for Alzheimer classification process. In this project we are going to use MRI along with PET scan and CNN (convolution neural network) for image classification into normal cognitive (NC).

Potential Application of MicroRNAs and Some Other Molecular Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is the world's most common neurodegenerative disease, expected to affect up to one-third of the elderly population in the near future. Among the major challenges in combating AD are the inability to reverse the damage caused by the disease, expensive diagnostic tools, and the lack of specific markers for the early detection of AD. This paper highlights promising research directions for molecular markers in AD diagnosis, including the diagnostic potential of microRNAs. The latest molecular methods for diagnosing AD are discussed, with particular emphasis on diagnostic techniques prior to the appearance of full AD symptoms and markers detectable in human body fluids. A collection of recent studies demonstrates the promising potential of molecular methods in AD diagnosis, using miRNAs as biomarkers. Up- or downregulation in neurodegenerative diseases may not only provide a new diagnostic tool but also serve as a marker for differentiating neurodegenerative diseases. However, further research in this direction is needed.

Progress on early diagnosing Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions. The disease follows a continuum, starting with preclinical stages, progressing to mild cognitive and behavioral impairment, ultimately leading to dementia. Early detection of AD is crucial for better diagnosis and more effective treatment. However, the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive, and mostly are still not able to detect early disease state. Consequently, there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD. Various non-cognitive manifestations, including behavioral abnormalities, sleep disturbances, sensory dysfunctions, and physical changes, have been observed in the preclinical AD stage before occurrence of notable cognitive decline. Recent research advances have identified several biofluid biomarkers as early indicators of AD. This review focuses on these non-cognitive changes and newly discovered biomarkers in AD, specifically addressing the preclinical stages of the disease. Furthermore, it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

CCADD: An online webserver for Alzheimer's disease detection from brain MRI

Alzheimer's disease (AD) imposes a growing burden on public health due to its impact on memory, cognition, behavior, and social skills. Early detection using non-invasive brain magnetic resonance images (MRI) is vital for disease management. We introduce CCADD (Corpus Callosum-based Alzheimer's Disease Detection), a user-friendly webserver that automatically identifies and segments the corpus callosum (CC) region from brain MRI slices. Extracted shape and size-based features of CC are fed into Support Vector Machines (SVM), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), K-Nearest Neighbor (KNN), and Artificial Neural Network (ANN) classifiers to predict AD or Mild Cognitive Impairment (MCI). Exhaustive benchmarking on ADNI data reveals high prediction accuracies for different AD severity levels. CCADD empowers clinicians and researchers for AD detection. This server is available at: http://www.hpppi.iicb.res.in/add.

Prediction of Alzheimer’s Disease with Retinal Images Using Deep Learning

Alzheimer's disease (AD) is a leading cause of mortality worldwide. Early detection and accurate diagnosis of AD are crucial for effective intervention and improved patient outcomes. Retinal imaging has emerged as a non-invasive and cost-effective technique for AD prediction. This study aims to develop a deep learning model using convolutional neural networks (CNNs) architecture to predict AD from retinal images. The proposed model leverages the capabilities of CNNs to automatically learn relevant features from retinal images.

Utilizing Profound Learning Methods for Alzheimer's Infection Discovery: An Exhaustive Survey

Alzheimer’s disease (AD) is a major public health issue around the world. It is a progressive disease that causes memory loss and cognitive decline. Early detection is essential for early intervention and treatment of AD. In recent years, there has been a surge in the use of deep learning techniques to analyze complex medical data. This includes neuroimaging data as well as genetic data. This has led to promising advances in the detection of AD. In this paper, we will review the application of various deep learning methods in the field of Alzheimer’s Disease. We will look at the challenges that traditional diagnostic methods face and how these challenges can be overcome by using deep learning approaches. We will also look at different deep learning architectures and data modalities and techniques used in the field of AD detection. Finally, we will look at limitations and future direction of the field to help researchers and practitioners to develop more accurate and effective AD detection methods. Keywords: Alzheimer's Disease, deep learning, neuroimaging, biomarkers, early detection, diagnosis.