Signs Of Alzheimer's Disease Research Articles

A deep CNN‐based approach for predicting MCI to AD conversion

AbstractBackgroundDeep convolutional neural networks (CNNs) have demonstrated a considerable ability to decode various biomedical signals, including 2D and 3D neuroimaging data. Magnetoencephalography‐based functional connectivity (MEG‐FC) is proven to be a useful tool in predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD), since early signs of AD may be hidden in the way neuronal activity is spatially distributed and coordinated among different brain regions. In the present work, we propose a deep learning approach for the early diagnosis of AD, able to capture the electrophysiological anomalies occurring before the conversion by exploit an image‐based coding of MEG‐FC data. The proposed approach has been tested on a set of resting‐state MEG recordings, from a longitudinal study (24 months between 2 MEG scans for each subject) involving 54 participants: 27 'progressive' patients (i.e., MCI at the time of the 1st scan converted to AD at the time of the 2nd scan), and 27 'static' patients (i.e., MCI at the time of the 1st scan remained MCI at the time of the 2nd scan).MethodMEG and MRI data have been gathered from the 54 patients using an Elekta Vectorview system and a General Electric 1.5T MRI scanner, respectively. Source reconstruction was performed with LCMV beamformer. The obtained neural MEG sources were anatomically parcellated into 90 ROIs according to the AAL atlas. Considering the signals stemming from the 90 ROIs we extracted the MEG‐FC measures (PLV and COR), for different frequency bands [Hz]: θ(4‐8), α(8‐12), β(12‐30), and γ(30‐55). MEG‐FC has been then coded into image‐based representations and hierarchically decomposed by means of the CNN layers of 'AlexNet'. Finally, different classification techniques have been tested as predictive modules.ResultWith the proposed approach we obtained an accuracy of 0.9 in discriminating ‘static’ from ‘progressive’ patients using MEG‐FC data from the first scan. The best classification results have been obtained using the Linear Discriminant Analysis and Support Vector Machine techniques.ConclusionThe classification of FC profiles mediated by hierarchical CNNs decomposition is a promising method for detecting the early neurophysiological anomalies characterizing the progression to AD.

Herpes simplex virus and early neuroimaging markers of Alzheimer’s disease: Hippocampal volume and white matter integrity

AbstractBackgroundWhile previous studies suggest an implication of herpes simplex virus in the onset of Alzheimer’s disease (AD), no study has investigated its association with early neuroimaging markers of AD. Moreover, a genetic susceptibility factor, the APOE4 status, is suspected to intervene in the entry of the virus into neurons and could partly explain why, despite a high seroprevalence, some infected individuals remain healthy carriers, while others develop neurological consequences of the infection. The present study aims to evaluate the association between HSV status and early neuroimaging markers of AD according to APOE4 status.MethodIn the AMI cohort, a population‐based prospective study on aging, the associations between HSV seroprevalence and i) hippocampal volume (n=172) and ii) white matter integrity in the parahippocampal cingulum and fornix (n=117), which are the main afferent and efferent axonal bundles of the hippocampus, were assessed according to APOE4 status. Serologies were performed at inclusion and magnetic resonance imaging scans were performed at 4 years of follow‐up. Right and left hippocampal volumes were averaged and expressed as a percentage of the total intracranial volume. White matter integrity was assessed using diffusion tensor imaging parameters: fractional anisotropy (FA) and mean diffusivity (MD). High FA and low MD values reflect a well‐organized and undamaged axon fiber architecture.ResultAmong APOE4 carriers, infected subjects presented lower hippocampal volumes (p=0.04) and higher microstructural alterations of the cingulum (lower FA, p=0.04; higher MD, p<0.01) than noninfected subjects; similar nonsignificant trends were observed for the fornix. Among APOE4 noncarriers, no associations were observed.ConclusionWhile the underlying mechanism remains uncertain and may involve direct action of the virus and/or the immune response against it, our findings suggest an association between HSV infection and early signs of AD among subjects with a genetic susceptibility factor, reinforcing the need to investigate the infectious hypothesis of AD and the potential related treatments.

PIH8 Primary Care Costs Due to Prodromal Alzheimer Disease: A Real-World Study in Patients with 10-Year or Longer Medical History

Little is known about the costs associated with the prodromal stages of dementia. The aim of this study is to estimate primary care costs triggered by Alzheimer disease (AD) prodromal signs and/or symptoms, during a 10-year or longer period preceding AD diagnosis, and compared them with costs cumulated in general population for the same signs and/or symptoms. This is a cohort study with a nested case-control analysis involving 1889 AD cases and 18890 controls aged 60 years or older, gathered from the Health Search Database (HSD), an Italian data source collecting primary care data. AD incident cases have been defined in accordance with ICD-9CM codes. Costs related to pharmacological treatment, diagnostic tests and specialist referrals triggered by prodromal AD signs and/or symptoms have been quantified and compared with costs cumulated by the same conditions in the general population aged 60 years or older In primary care patients developing AD, during the pre-diagnosis 10-year or longer period, prodromal signs and symptoms trigger diagnostic and therapeutic costs that are 55% significantly higher than those cumulated in general population for the same clinical reasons. After accounting for patients’ comorbidity burden and regional differences, the mean cost related to diagnostic and therapeutic procedures, and those related to specialist referrals, amounted to 854.1 € (SD: 630.6 €) in AD incident cases vs. 527.3 € (SD: 446.2) in control cases. Prodromal AD manifestations are associated to primary care costs that resulted higher than those cumulated in the general population aged 60 years or older for the same clinical reasons. A better interpretation of such signs and symptoms might aid GPs to set more precise and timely diagnostic pathways, as well as health care systems to optimize resource allocation when planning prevention and care paths for people at risk of cognitive decline.

Electromagnetic Field in Alzheimer's Disease: A Literature Review of Recent Preclinical and Clinical Studies.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloid-beta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Cats and Apples: Semantic Fluency Performance for Living Things Identifies Patients with Very Early Alzheimer's Disease.

Objective: Reduced semantic memory performance is a known neuropsychological marker of very early Alzheimer’s disease (AD), but the task format that best predicts disease status is an open question. The present study aimed to identify the semantic fluency task and measure that best discriminates early-stage AD patients (PATs) from cognitively healthy controls. Method: Semantic fluency performance for animals, fruits, tools, and vehicles was assessed in 70 early-stage AD PATs and 67 cognitively healthy participants. Logistic regressions and receiver operating characteristics were calculated for five total score semantic fluency measures. Results: Compared with all other measures, living things (i.e., total correct animals + total correct fruits) achieved highest z-statistics, highest area under the curve and smallest difference between the upper and lower 95% confidence intervals. Conclusion: Living things total correct is a powerful tool to detect the earliest signs of incipient AD.

Роль beta-амілоїду в нормі та при хворобі Альцгеймера

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and memory loss. The pathogenesis of AD is complex, depends on many factors, and has not yet been fully studied. Extracellular deposits of amyloid-beta (Ab) peptide in the form of senile plaques, the formation of intracellular neurofibrillary tangles, and massive neuronal loss are considered as the main pathological signs of AD. However, recently there have been many data that indicate other pathways involved in the pathogenesis of AD. This review aims to analyze the existing data on the physiological role of Ab in the brain under normal conditions and its pathological role in Alzheimer’s disease.

Computational Modeling of Catecholamines Dysfunction in Alzheimer's Disease at Pre-Plaque Stage.

Background:Alzheimer’s disease (AD) etiopathogenesis remains partially unexplained. The main conceptual framework used to study AD is the Amyloid Cascade Hypothesis, although the failure of recent clinical experimentation seems to reduce its potential in AD research.Objective:A possible explanation for the failure of clinical trials is that they are set too late in AD progression. Recent studies suggest that the ventral tegmental area (VTA) degeneration could be one of the first events occurring in AD progression (pre-plaque stage).Methods:Here we investigate this hypothesis through a computational model and computer simulations validated with behavioral and neural data from patients.Results:We show that VTA degeneration might lead to system-level adjustments of catecholamine release, triggering a sequence of events leading to relevant clinical and pathological signs of AD. These changes consist first in a midfrontal-driven compensatory hyperactivation of both VTA and locus coeruleus (norepinephrine) followed, with the progression of the VTA impairment, by a downregulation of catecholamine release. These processes could then trigger the neural degeneration at the cortical and hippocampal levels, due to the chronic loss of the neuroprotective role of norepinephrine.Conclusion:Our novel hypothesis might contribute to the formulation of a wider system-level view of AD which might help to devise early diagnostic and therapeutic interventions.

Association of microbiota-derived propionic acid and Alzheimer's disease; bioinformatics analysis.

Microbiota-derived metabolites could alter the brain tissue toward the neurodegeneration disease. This study aims to select the genes associated with Propionic acid (PPA) and compromise Alzheimer's disease (AD) to find the possible roles of PPA in AD pathogenesis. Microbiota-derived metabolites could alter the brain tissue toward the neurodegeneration disease. This study aims to select the genes associated with Propionic acid (PPA) and compromise Alzheimer's disease (AD) to find the possible roles of PPA in AD pathogenesis. Amongst all genes associated with PPA and AD, 284 genes to be shared by searching databases and were subjected to further analysis. AD-PPA genes mainly involved in cancer, bacterial and virus infection, and neurological and non-neurological diseases. Gene Ontology and pathway analysis covered the most AD hallmark, such as amyloid formation, apoptosis, proliferation, inflammation, and immune system. Network analysis revealed hub and bottleneck genes. MCODE analysis also indicated the seed genes represented in the significant subnetworks. ICAM1 and CCND1 were the hub, bottleneck, and seed genes. PPA interacted genes implicated in AD act through pathways initiate neuronal cell death. In sum up, AD-PPA shared genes exhibited evidence that supports the idea PPA secreted from bacteria could alter brain physiology toward the emerging AD signs. This idea needs to confirm by more future investigation in animal models.

Older Adult Demographics Unrelated to Alzheimer’s Disease Warning Signs

Abstract Objectives To determine whether demographics such as age, race, and gender are related to Alzheimer's disease (AD) warning signs in adults over the age of 50. Methods Adults aged 50+ were asked to complete a survey including: demographics (age, gender, marital status, living situation, race, and education), health, and AD warning signs experienced in the previous year. Surveys were distributed in person and online via social media and email. SPSS 26 was used to run one-way ANOVA and Pearson's correlations. Results There was no relationship or difference between any of the demographic variables and warning signs of AD experienced over the previous year. There was a difference between groups based on living situation (F = 3.701 [2, 85], P = 0.029), which disappeared when outliers were excluded. Conclusions There is no significant relationship between the number of warning signs of AD experienced by any demographic variables, including age, when outliers are controlled for, contradicting previous studies that listed age, race, and gender as risk factors. Since demographic data are not related to AD symptoms, it is necessary to include cognitive assessment as part of health screenings for older adults before symptoms impact activities of daily living. Funding Sources None.

An Incidental Learning Method to Improve Face-Name Memory in Older Adults With Amnestic Mild Cognitive Impairment.

Forgetting names is a common memory concern for people with amnestic mild cognitive impairment (aMCI) and is related to explicit memory deficits and pathological changes in the medial temporal lobes at the early stages of Alzheimer's disease (AD). In the current experiment, we tested a unique method to improve memory for face-name associations in people with aMCI involving incidental rehearsal of face-name pairs. Older adults with aMCI and age- and education-matched controls learned 24 face-name pairs and were tested via immediate cued recall with faces as cues for associated names. During a 25- to 30-min retention interval, 10 of the face-name pairs reappeared as a quarter of the items on a seemingly unrelated 1-back task on faces, with the superimposed names irrelevant to the task. After the delay, surprise delayed cued recall and forced-choice associative recognition tests were administered for the face-name pairs. Both groups showed reduced forgetting of the names that repeated as distraction and enhanced recollection of these pairs. The results demonstrate that passive methods to prompt automatic retrieval of associations may hold promise as interventions for people with early signs of AD.

Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer's Disease: Are Irreversible Inhibitors the Future?

Decades of research have produced no effective method to prevent, delay the onset, or slow the progression of Alzheimer’s disease (AD). In contrast to these failures, acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors slow the clinical progression of the disease and randomized, placebo-controlled trials in prodromal and mild to moderate AD patients have shown AChE inhibitor anti-neurodegenerative benefits in the cortex, hippocampus, and basal forebrain. CNS neurodegeneration and atrophy are now recognized as biomarkers of AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria and recent evidence shows that these markers are among the earliest signs of prodromal AD, before the appearance of amyloid. The current AChE inhibitors (donepezil, rivastigmine, and galantamine) have short-acting mechanisms of action that result in dose-limiting toxicity and inadequate efficacy. Irreversible AChE inhibitors, with a long-acting mechanism of action, are inherently CNS selective and can more than double CNS AChE inhibition possible with short-acting inhibitors. Irreversible AChE inhibitors open the door to high-level CNS AChE inhibition and improved anti-neurodegenerative benefits that may be an important part of future treatments to more effectively prevent, delay the onset, or slow the progression of AD.

THE EFFECT OF BETAINE AND PIPERINE ON RATS WITH CREATED ALZHEIMER- LIKE DEMENTIA BY AF64A

OBJECTIVE: The great majority of dementia patients (about 60-70%) suffer from Alzheimer disease (AD). The distinctive pathological signs of AD are senile plaques (SPs), neurofibrillary tangles (NFTS), synaptic loss and neurodegeneration. In this study; it is aimed to determine the damage caused by Acetylcholine Mustard Aziridin Ion (AF64A), which induces neurological anomalies, and the therapeutic effect of antioxidant piperine and betaine.MATERIAL AND METHODS: In this study; 24 Sprague-Dawley male rats were used and 4 groups were formed: Group 1 consisting of healthy rats (control, n = 6); Group 2 (n = 6) with experimental dementia induced by AF64A, group 3 (AF64A betaine, n = 6) treated with betaine and 4 (AF64A piperine, n = 6) treated with piperine. The mRNA levels of mitogen activated protein kinase-1 (MAPK-1) in hippocampus tissue, Malondialdehyde (MDA) levels in liver and blood serum samples and reduced glutathione (GSH) levels in liver and erythrocyte samples were investigated. In addition, behavioral differences were determined in terms of duration using the morris water maze test.RESULTS: The highest GSH levels in liver and erythrocytes were determined in piperine-treated group 4 (p <0.01). The highest results were recorded in group 2 and the lowest results were recorded in group 4 (p <0.05) in terms of liver and plasma MDA levels. The best results in brain tissue pathology findings were also observed in the piperine applied group (p <0.05). There was a significant increase in hippocampus MAPK-1 mRNA levels in group 2 whereas a decrease in group 4.CONCLUSIONS:Determined pathological, biochemical and genetic analyzes beside the longest reaction time in the behavior test result showed that the use of AF64A significantly destroys the brain nerve cell. But especially piperine treatment create almost reversible effect onto AF64A damaging act via bring down all negative signs into control level compare to the betaine effect. AF64A application causes a significant level of brain damage in rats, creating a similar effect to Alzheimer's. As an alternative treatment, it shows that the application of betaine and piperine reduces all the negative consequences of AF64A, especially the application of piperine, to almost completely normal levels. These findings indicate that the use of antioxidant piperine may be beneficial in reducing and/or regressing oxidant effects in dementia and especially in AD.

Herpes virus causes signs of Alzheimer's

Herpes virus causes signs of Alzheimer's

Effects of Delphinidin on Pathophysiological Signs of Nucleus Basalis of Meynert Lesioned Rats as Animal Model of Alzheimer Disease.

Alzheimer's disease (AD) is an advanced neurodegenerative disorder greatly accompanied by cognitive deficits, oxidative stress, inflammation, amyloid plaques deposition, and acetylcholinesterase (AChE) hyper-activation. Growing evidence suggests natural compounds with antioxidant and anti-inflammatory features improve pathophysiological signs of AD. The present study was designed to investigate the effects of Delphinidin (25, 50mg/kg) as an anthocyanidin on spatial memory impairment and AD hallmarks such as hippocampal AChE activity, amyloid plaques deposition, oxidative stress and expression of amyloid precursor protein (APP), AChE, and amyloid beta (Aβ) proteins in nucleus basalis of Meynert (NBM) lesioned rats as the most prevalent animal model of AD. Interestingly, Delphinidin-treated animals showed a significant decrease in escape latency and distance moved. Furthermore, in probe test, NBM lesioned rats treated with both doses of Delphinidin spent more time in the target quadrant zone in Morris water maze task. It could also interact with catalytic site of AChE enzyme and inhibits acetylcholine hydrolysis in in vitro and in vivo conditions. In addition, Delphinidin could scavenge additional produced reactive oxygen molecules dose dependently. Our immunoblotting analysis confirmed high dose of Delphinidin reduced AChE, APP and Aβ contents in AD model. Staining of hippocampus tissue revealed that Delphinidin treatment decreased amyloid plaques formation in NBM lesion rats. It seems that Delphinidin is a plate-like molecule intercalated between β-plated sheets related to Aβ molecules and inhibited amyloid fibril formation. Altogether, Delphinidin and Delphinidin-rich fruits could be suggested as a therapeutic adjuvant in AD and other related cognitive disorders.

Editors' note: INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease

In the article, “INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease”, Meyer et al. reported that low-dose naproxen did not significantly reduce the progression of a composite indicator of presymptomatic Alzheimer Disease (AD)—the Alzheimer Progression Score (APS)—in a 2-year double-blind randomized placebo-controlled trial that enrolled 195 cognitively intact elderly participants with a family history of AD. In response, Dr. Ashford posits that the observed epidemiologic association of nonsteroidal anti-inflammatory drugs (NSAIDs) with decreased risk of AD may be related to the effect of these drugs on gamma-secretase rather than on inflammation, citing previous work showing that flurbiprofen and ibuprofen lower amyloidogenic Abeta42 independently of cyclooxygenase activity. He postulates that several years of treatment may be required to observe a benefit and wonders whether ibuprofen may be a better drug to test than naproxen. He also highlights the need for better tools to more accurately assess treatment effects in early AD. Responding to these comments, Drs. Breitner et al. noted that a meta-analysis of 6 prospective studies showed no significant differences in apparent risk modification of AD between gamma secretase-modifying and non-gamma secretase-modifying NSAIDS and suggested no difference between exposure to naproxen vs ibuprofen. Although they acknowledge that INTREPAD lacked an initially estimated degree of power, they note that the APS captured significant progression of apparent AD signs over the course of the trial and allowed a reasonably precise estimate of a lack of treatment effect, with naproxen also having no benefit on any of the APS components. With the largely unimpressive results of antiamyloid treatment strategies to date in AD, interest in alternative therapeutic targets, including anti-inflammatory strategies, is likely to continue growing in the coming years. In the article, “INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease”, Meyer et al. reported that low-dose naproxen did not significantly reduce the progression of a composite indicator of presymptomatic Alzheimer Disease (AD)—the Alzheimer Progression Score (APS)—in a 2-year double-blind randomized placebo-controlled trial that enrolled 195 cognitively intact elderly participants with a family history of AD. In response, Dr. Ashford posits that the observed epidemiologic association of nonsteroidal anti-inflammatory drugs (NSAIDs) with decreased risk of AD may be related to the effect of these drugs on gamma-secretase rather than on inflammation, citing previous work showing that flurbiprofen and ibuprofen lower amyloidogenic Abeta42 independently of cyclooxygenase activity. He postulates that several years of treatment may be required to observe a benefit and wonders whether ibuprofen may be a better drug to test than naproxen. He also highlights the need for better tools to more accurately assess treatment effects in early AD. Responding to these comments, Drs. Breitner et al. noted that a meta-analysis of 6 prospective studies showed no significant differences in apparent risk modification of AD between gamma secretase-modifying and non-gamma secretase-modifying NSAIDS and suggested no difference between exposure to naproxen vs ibuprofen. Although they acknowledge that INTREPAD lacked an initially estimated degree of power, they note that the APS captured significant progression of apparent AD signs over the course of the trial and allowed a reasonably precise estimate of a lack of treatment effect, with naproxen also having no benefit on any of the APS components. With the largely unimpressive results of antiamyloid treatment strategies to date in AD, interest in alternative therapeutic targets, including anti-inflammatory strategies, is likely to continue growing in the coming years.

Cognitive Functions as Predictors of Alzheimer's Disease Biomarker Status in the European Prevention of Alzheimer's Dementia Cohort.

Alterations in Alzheimer's disease (AD) biomarkers have been observed decades before the onset of dementia. Cognitive dysfunction, while central to the clinical diagnosis of AD, has long been considered as a late-stage phenomenon. This assumption is currently challenged and signals on some cognitive tests are now being observed within the preclinical stage. As part of the European Prevention of Alzheimer's Dementia (EPAD) project, a battery of cognitive tests has been proposed (the EPAD Neuropsychological Examination, ENE) which is designed to detect cognitive changes in persons without clinical signs of AD but who are at high risk. Analysis of results from the 361 participants with complete measures and without dementia recruited into the EPAD Longitudinal Cohort Study showed that the majority have elevated biomarker levels, with significant associations between an episodic verbal memory task and tau, while amyloid-β (Aβ) was associated with a central executive task. These preliminary findings suggest that profiles of cognitive performance may be specific to a given biomarker, with a primarily hippocampal task being associated with higher levels of tau and a frontal executive task being associated with higher levels of Aβ. While previous research has focused on the relationship between cognition and levels of Aβ, our findings suggest that p-tau may potentially be a more significant correlate.

Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention.

Significance: Epidemiological studies indicate that metabolic disorders are associated with an increased risk for Alzheimer's disease (AD). Metabolic remodeling occurs in the central nervous system (CNS) and periphery, even in the early stages of AD. Mitochondrial dysfunction has been widely accepted as a molecular mechanism underlying metabolic disorders. Therefore, focusing on early metabolic changes, especially from the perspective of mitochondria, could be of interest for early AD diagnosis and intervention. Recent Advances: We and others have identified that the levels of several metabolites are fluctuated in the periphery before their accumulation in the CNS, which plays an important role in the pathogenesis of AD. Mitochondrial remodeling is likely one of the earliest signs of AD, linking nutritional imbalance to cognitive deficits. Notably, by improving mitochondrial function, mitochondrial nutrients efficiently rescue cellular metabolic dysfunction in the CNS and periphery in individuals with AD. Critical Issues: Peripheral metabolic disorders should be intensively explored and evaluated for the early diagnosis of AD. The circulating metabolites derived from mitochondrial remodeling represent novel potential diagnostic biomarkers for AD that are more readily detected than CNS-oriented biomarkers. Moreover, mitochondrial nutrients provide a promising approach to preventing and delaying AD progression. Future Directions: Abnormal mitochondrial metabolism in the CNS and periphery is involved in AD pathogenesis. More clinical studies provide evidence for the suitability and reliability of circulating metabolites and cytokines for the early diagnosis of AD. Targeting mitochondria to rewire cellular metabolism is a promising approach to preventing AD and ameliorating AD-related metabolic disorders.

Retinal microvascular attenuation in mental cognitive impairment and Alzheimer's disease by optical coherence tomography angiography.

To explore regional variation of the macular microvasculature in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), also to detect the association between retinal macular microvascular parameters and the progress of preclinical AD. Prospective study of healthy controls, patients with MCI and patients with AD by using Optical coherence tomography angiography (OCT-A). We quantified foveal avascular zone (FAZ) areas, densities of the superficial retinal capillary plexuses (SRCP) and deep retinal capillary plexuses (DRCP). The SRCP and DRCP were divided into inner (3mm) and external (6mm) annular rings, each containing four quadrants (SI, II, TI, NI, SE, IE, TE and NE). The data were analysed statistically by using SPSS 22 software. Totally, 60 subjects including 21 HC (33 eyes), 21 patients with MCI (32 eyes) and 18 AD patients (28 eyes) were recruited. The microvascular densities of DRCP at all quadrants of the parafovea and perifovea were significantly lower in AD patients compared to HC group (p<0.05). Compared to the HCs, MCI patients showed significant microvascular loss in most sectors of the parafovea and the SE sector of the DRCP (p<0.05), but not in the parafovea (p=0.829) or perifovea (p=0.824) of the SRCP. No significant difference was found in microvascular density of SRCP among the groups, except at SI between the AD and HC groups (p=0.048). Our findings demonstrated the macular microvascular attenuation in MCI and AD patients. Both AD and MCI patients showed retinal microvascular density loss, which is more significant in the deep retinal capillary plexuses. Optical coherence tomography angiography (OCT-A) can be used to identify early microvascular abnormalities in AD and MCI. Quantified microvascular density in the DRCP might serve as potential biomarkers of early sign of AD then contribute to forestall the progression of preclinical AD.

A combination of 3-D discrete wavelet transform and 3-D local binary pattern for classification of mild cognitive impairment

BackgroundThe detection of Alzheimer’s Disease (AD) in its formative stages, especially in Mild Cognitive Impairments (MCI), has the potential of helping the clinicians in understanding the condition. The literature review shows that the classification of MCI-converts and MCI-non-converts has not been explored profusely and the maximum classification accuracy reported is rather low. Thus, this paper proposes a Machine Learning approach for classifying patients of MCI into two groups one who converted to AD and the others who are not diagnosed with any signs of AD. The proposed algorithm is also used to distinguish MCI patients from controls (CN). This work uses the Structural Magnetic Resonance Imaging data.MethodsThis work proposes a 3-D variant of Local Binary Pattern (LBP), called LBP-20 for extracting features. The method has been compared with 3D-Discrete Wavelet Transform (3D-DWT). Subsequently, a combination of 3D-DWT and LBP-20 has been used for extracting features. The relevant features are selected using the Fisher Discriminant Ratio (FDR) and finally the classification has been carried out using the Support Vector Machine.ResultsThe combination of 3D-DWT with LBP-20 results in a maximum accuracy of 88.77. Similarly, the proposed combination of methods is also applied to distinguish MCI from CN. The proposed method results in the classification accuracy of 90.31 in this data.ConclusionThe proposed combination is able to extract relevant distribution of microstructures from each component, obtained with the use of DWT and thereby improving the classification accuracy. Moreover, the number of features used for classification is significantly less as compared to those obtained by 3D-DWT. The performance of the proposed method is measured in terms of accuracy, specificity and sensitivity and is found superior in comparison to the existing methods. Thus, the proposed method may contribute to effective diagnosis of MCI and may prove advantageous in clinical settings.

Retinal imaging think tank convened by the Alzheimer's Association to examine its promise in the early detection of Alzheimer's.

Retinal changes are evident throughout the progression of Alzheimer's disease (AD), including the presence of amyloid plaques and neurofibrillary tangles, microvascular changes, evidence of inflammation, and other changes in retinal metabolism. Researchers have also found that retinal imaging may detect signs of underlying neurodegenerative disease even before cognitive impairment is present. Other studies show that non-invasive retinal imaging—including, but not limited to, optical coherence tomography—is a potential inexpensive and patient-friendly tool for screening for signs of AD. To help bring these potential new biomarkers to the forefront of research discussion, the Alzheimer's Association in collaboration with the editorial team from Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) convened the “Retinal Imaging and Neurodegenerative Diseases” workshop in May 2019 in Washington, DC. This first-of-its-kind international event brought together 90 researchers from nine countries. The American Optometric Association (AOA) published a report from the workshop in its publication, Primary Care Optometry News.1 Workshop participants discussed multiple imaging modalities and methods, identified areas of data convergence, and explored gaps and potential areas to further advance application of these technologies for clinical trials and diagnostic uses. According to co-chairs Peter J. Snyder, PhD, editor-in-chief of DADM and vice president of research and economic development, University of Rhode Island, and Heather Snyder, PhD, vice president of medical science relations at the Alzheimer's Association, having this workshop is a critical step toward advancing research on retinal changes that may be uniquely amenable to non-invasive ocular imaging. The next step is to advance necessary research to further validate retinal/ocular non-invasive biomarkers. During the day-and-a-half meeting, researchers discussed a wide range of subjects including the quantification of amyloid beta and tau structures; advanced use of 3D macular scans and blood flow measurement; disease-related changes to the structure of retinal neuronal layers, vascular bed changes, and emerging imaging technologies (eg, cross-polarized light imaging, hyperspectral retinal imaging, and fluorescence lifetime imaging ophthalmoscopy); real-world trials of retinal imaging; microglia activation at the preclinical disease stage and imaging of neuroinflammation in the retina; the relationship between sleep disturbances and melanopsin-retinal ganglion cell degeneration; and how best to approach a consensus across research groups with respect to a “standard minimum dataset” to accelerate collaborative efforts. The AOA's chief public health officer, Michael Dueñas, OD, who participated in the workshop, said, “One day Alzheimer's disease could be another significant responsibility for optometry within team-based medical care. Pairing retinal imaging technology and our understanding of early cognitive decline is going to be essential in raising our patients’ health outcomes and preventing or slowing neurodegenerative disease.” A detailed white paper of the proceedings of this workshop is in process.