Research progress in assisting in the diagnosis of early Alzheimer's disease through eye structure / 国际眼科杂志(Guoji Yanke Zazhi)

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

Effects of pranlinide on cognitive behavior, β amyloid protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice / 解剖学报

[Abstract] Objective To study the effects of pranlinide on cognitive behavior, β amyloid(Aβ) protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice. Methods Thirty two 5×FAD mice and 16 WT mice were selected. All were female. 5×FAD mice were randomly divided into blank group and treatment group; No treatment was given in WT group. Blank group was intraperitoneally injected with PBS; treatment group was received intraperitoneal injection of pranlinide once a day for 8 weeks. The changes of cognitive ability were measured by Morris water maze test. The expression of Aβ6E10 protein in mice hippocampal cells and retina was detected by immunohistochemistry. Tumor necrosis factor α(NF-α) was determined by enzyme-linked immunosorbent assay. The same method was also used for interleukin-1β(IL-1β) detection (The content of inflammatory factors). The arrangement and morphology of nerve cells in mouse hippocampal tissue were determined by hematoxylin-eosin (HE) staining. Results The latency time of treatment group was shorter than that of 5×FAD group,and the times of crossing the platform and the percentage of target quadrant stay in the treatment group were higher than those in the 5×FAD group, and the differences were statistically significant (P0. 05). Compared with the 5×FAD group, the nerve cells in the treatment group were arramged in order and clear relatively. The distribution of glial cells was concentrated; The surrounding clearance was small. Conclusion Pranlinide can improve the cognitive ability of mice. The arrangement of nerve cells is regular, the shape is regular and the boundary is clear; The distribution of glial cells is concentrated; surrounding of clearance decrease. Aβ6E10 is synchronized in brain and retina.

Through the eyes into the brain, using artificial intelligence

INTRODUCTION@#Detection of neurological conditions is of high importance in the current context of increasingly ageing populations. Imaging of the retina and the optic nerve head represents a unique opportunity to detect brain diseases, but requires specific human expertise. We review the current outcomes of artificial intelligence (AI) methods applied to retinal imaging for the detection of neurological and neuro-ophthalmic conditions.@*METHOD@#Current and emerging concepts related to the detection of neurological conditions, using AI-based investigations of the retina in patients with brain disease were examined and summarised.@*RESULTS@#Papilloedema due to intracranial hypertension can be accurately identified with deep learning on standard retinal imaging at a human expert level. Emerging studies suggest that patients with Alzheimer's disease can be discriminated from cognitively normal individuals, using AI applied to retinal images.@*CONCLUSION@#Recent AI-based systems dedicated to scalable retinal imaging have opened new perspectives for the detection of brain conditions directly or indirectly affecting retinal structures. However, further validation and implementation studies are required to better understand their potential value in clinical practice.

Optical coherence tomography in neurodegenerative disorders / Tomografia de coerência óptica em doenças neurodegenerativas

ABSTRACT Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.

RESUMO A avaliação estrutural do cérebro, feita por meio dos exames de neuroimagem, é a forma mais utilizada de ferramenta diagnóstica e de acompanhamento das doenças neurodegenerativas. Técnicas de imagem mais sofisticadas podem ser necessárias especialmente nas fases mais precoces, antes mesmo do surgimento de quaisquer sintomas, porém costumam ser caras e pouco acessíveis. Sendo assim, é de fundamental importância a busca de biomarcadores não invasivos, de fácil acesso e baixo custo, que possam ser utilizados para rastreio populacional e diagnóstico mais precoce. Nesse cenário, o número de estudos com ênfase em técnicas de imagem para avaliação estrutural da retina em pacientes com doenças neurodegenerativas tem aumentado nos últimos anos. A retina apresenta similaridade embriológica, histológica, bioquímica, microvascular e neurotransmissora com o córtex cerebral, tornando-se assim um biomarcador único e promissor nas doenças neurodegenerativas. A tomografia de coerência óptica é uma moderna técnica de imagem não invasiva que gera imagens seccionais bidimensionais de alta resolução e medidas volumétricas tridimensionais reprodutivas do disco óptico e da mácula. Essa tecnologia é amplamente utilizada na prática oftalmológica para o diagnóstico e o seguimento de diversas doenças oculares, como glaucoma, retinopatia diabética e degeneração macular relacionada à idade. A redução da espessura da camada de fibras nervosas da retina e das camadas de células ganglionares em pacientes com doenças neurodegenerativas foi demonstrada em diversos estudos clínicos nos últimos anos. Nesta revisão, abordamos as principais aplicações clínicas da tomografia de coerência óptica nas doenças neurodegenerativas e discutimos o seu papel como potencial biomarcador nessas afecções.

Ocular images for neurodegenerative disease analysis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retina and optic nerve both originate in brain, therefore they have the similar structure and functional characteristics of the brain. Exploring the performance of the central optic nervous disorder on the retina will be beneficial to uncovering the interaction mechanism between brain and eye. As an extension of the central nervous system, the retina contains ganglion cell, a special neuron, whose axon form the optic nerve and has access into the central nervous system. Therefore, the retina can be used as a mirror reflecting neurodegenerative diseases structurally and functionally. With the development of imaging technology, optical coherence tomography(angiography)has become the mainstream tool for ophthalmological clinical diagnosis due to its easy operation and low cost. In recent years, discovering biomarkers of neurodegenerative diseases, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis and so on, in the retinal optical coherence tomography images has gradually become an emerging research direction. In this review, we summarized the research progress of neurodegenerative diseases analysis based on the retinal images in the past decade, and provide a prospect to inspire further research as far as possible.

Retinal optical coherence tomography and optical coherence tomography angiography in Alzheimer's disease / 中华行为医学与脑科学杂志

Alzheimer's disease (AD) is the most common cause of dementia. With population aging, AD has become one of the urgent public health problems worldwide. The retina as a " window" to the brain dysfunction. Studies based on optical coherence tomography/ optical coherence tomography angiography(OCT/OCTA) imaging technology have shown that retinal vascular and structure were significantly changed in patients with clinical and preclinical AD. The changes of retinal vascular and structure were also significantly correlated with cognitive scores, cerebral degeneration, and the decline of cognitive function. These findings suggest that ocular structure and vascular changes based on OCT/OCTA imaging can provide non-invasive, inexpensive and practical biomarkers for early diagnosis of AD. This article reviews the research status and limitations of retinal structure and vascular changes in AD based on OCT/OCTA, in order to provide new ideas and methods for early dingnosis of AD.

Use of ocular biomarkers as a potential tool for early diagnosis of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide which unfortunately has no known effective cure to date. Despite many clinical trials indicating the effectiveness of preclinical treatment, a sensitive tool for screening of AD is yet to be developed. Due to multiple similarities between ocular and the brain tissue, the eye is being explored by researchers for this purpose, with utmost attention focused on the retinal tissue. Besides visual functional impairment, neuronal degeneration and apoptosis, retinal nerve fiber degeneration, increase in the cup-to-disc ratio, and retinal vascular thinning and tortuosity are the changes observed in the retinal tissue which are related to AD. Studies have shown that targeting these changes in the retina is an effective way of reducing the degeneration of retinal neuronal tissue. Similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Multiple studies are underway to investigate the potential of diagnosing AD and detection of amyloid-? (A?) levels in the retinal tissue. Since the tissues in the anterior segment of the eye are more accessible for in vivo imaging and examination, they have more potential as screening biomarkers. This article provides a concise review of available literature on the ocular biomarkers in anterior and posterior segments of the eye including the cornea, aqueous humour (AH), crystalline lens, and retina in AD. This review will also highlight the newer technological tools available for the detection of potential biomarkers in the eye for early diagnosis of AD.

Application of OCTA in the detection of retinal microvascular changes in Alzheimer's disease in preclinical stage / 国际眼科杂志(Guoji Yanke Zazhi)

@#Alzheimer's disease(AD)is one of the most common causes of Dementia in the world, with symptoms often appearing years after the degenerative changes in the brain. Therefore, the early diagnosis of AD is difficult and the previous diagnostic methods are generally invasive. Considering that most patients with AD are accompanied by visual impairment, the retina can be regarded as a window into the brain. Recently, optical coherence tomography(OCTA)can be used for noninvasive and rapid assessment of structure within different vascular plexuses in the retina and choroid. This improves our understanding of neurological diseases, and more likely contributes to the early diagnosis of AD patients. This paper reviewed the relevant literatures on the application of OCTA in the study of neurological diseases, as well as the structure and function of the brain and retina in patients with AD.

Research progress of ophthalmic examination in the diagnosis of Alzheimer's disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Alzheimer's disease(AD)is a neurological degenerative disease that is insidious onset. The main pathological features are deposition of amyloid β(Aβ)and intracellular hyperphosphorylated tau protein. In recent years, studies have found that the manifestations of AD exist not only in the brain but also in the eyes, such as impaired visual function, changes in the pupil, Aβ deposition in the lens, changes in the retina and choroid, and so on. These ocular manifestations provide clues to the early diagnosis of AD and have positive clinical and social significance. Therefore, this article reviews the ocular manifestations of AD and their use as biomarkers for diagnosis and progression.

Research progress of advanced glycation end products in glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Advanced glycation end products(AGEs)accumulate in various tissues in the body, and induce a series of biological responses by regulating the expression of related factors and activating signal pathways, causing age-related diseases and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Atherosclerosis. Glaucoma, which is the leading cause of vision loss after cataract worldwide, is a degenerative disease of the optic nerve that ultimately leads to irreversible visual field loss. The accumulation of excessive AGE sin the retina and other eye tissues of glaucoma patients activates signal pathways and triggers biological responses, causing damage to the structure and function of tissues and cells, and participating in the pathogenesis of glaucoma. This article mainly describes the latest progress of AGEs in glaucoma pathogenesis, treatment, screening and other related research, and provides new ideas and research methods for the prevention and treatment of glaucoma.

Advance in Visual Dysfunction for Alzheimer's Disease (review) / 中国康复理论与实践

In recent years, it is found that β-amyloid deposites in the retina of patients with Alzheimer's disease (AD), synchronizing with intracranial changes. AD patients lose their visual acuity and visual contrast sensitivity and demonstrate glaucoma-like visual field loss, color vision disorder, visual hallucination and visual space damage, etc. The retinas become thinner, the latency of electroretinogram prolongs with amplitude decrease, and the latency of visual-evoked potential prolongs.

Progress in the application of oximetry in retinal diseases / 中华眼底病杂志

The retinal blood oxygen quantification method is a fast and non-invasive new retinal vascular imaging technology, which is used to reflect the metabolism of retinal blood oxygen and the micro-circulation of whole body by measuring, analyzing and quantifying the blood oxygen saturation of the main arteries and veins of the retina. The circulation state provides a reliable basis for medical diagnosis. Retinal blood oxygen saturation can be used as a biomarker for the diagnosis and evaluation of ophthalmologic and brain diseases such as diabetic retinopathy, central retinal vein occlusion, retinitis pigmentosa, glaucoma and Alzheimer's disease.

Research progress of ophthalmic examination in the diagnosis of Alzheimer's disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Alzheimer's disease(AD)is a neurological degenerative disease that is insidious onset. The main pathological features are deposition of amyloid β(Aβ)and intracellular hyperphosphorylated tau protein. In recent years, studies have found that the manifestations of AD exist not only in the brain but also in the eyes, such as impaired visual function, changes in the pupil, Aβ deposition in the lens, changes in the retina and choroid, and so on. These ocular manifestations provide clues to the early diagnosis of AD and have positive clinical and social significance. Therefore, this article reviews the ocular manifestations of AD and their use as biomarkers for diagnosis and progression.

Research progress of advanced glycation end products in glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Advanced glycation end products(AGEs)accumulate in various tissues in the body, and induce a series of biological responses by regulating the expression of related factors and activating signal pathways, causing age-related diseases and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Atherosclerosis. Glaucoma, which is the leading cause of vision loss after cataract worldwide, is a degenerative disease of the optic nerve that ultimately leads to irreversible visual field loss. The accumulation of excessive AGE sin the retina and other eye tissues of glaucoma patients activates signal pathways and triggers biological responses, causing damage to the structure and function of tissues and cells, and participating in the pathogenesis of glaucoma. This article mainly describes the latest progress of AGEs in glaucoma pathogenesis, treatment, screening and other related research, and provides new ideas and research methods for the prevention and treatment of glaucoma.

Clinical research progress on ocular fundus changes occur in Alzheimer's disease / 中华眼底病杂志

Alzheimer's disease is a common neuro-degenerative disease.The clinical diagnosis mainly depends on the patient's complaint,the score of mini-mental state examination and Montreal cognitive assessment scale,and the comprehensive judgment of MRI and other imaging examinations.Retina is homologous to brain tissue,and their vascular systems have similar physiological characteristics to small blood vessels in the brain.Numerous studies found that the thickness of retinal nerve fiber layer,visual function,retinal blood vessels and retinal oxygen saturation were changed in AD patients to different degrees.To explore the formation mechanism and significance of ocular fundus changes in AD patients will be helpful to select specific,sensitive and simple methods for early observation and evaluation of AD.

Folate/Vitamin B Alleviates Hyperhomocysteinemia-Induced Alzheimer-Like Pathologies in Rat Retina / 神经科学通报·英文版

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.

Características cognitivas y oculares en enfermedad de Alzheimer / Cognitive and ocular characteristics in Alzheimer's disease

Resumen La enfermedad de Alzheimer/AD es un trastorno neurodegenerativo progresivo que afecta la memoria y todas las funciones cognitivas con una edad de inicio tardío o precoz, y se presenta con una muy baja frecuencia por causa genética por alteración en el gen de la PPA, PS1 O PS2. El elemento etiológico mayor conocido es genético, con múltiples factores de susceptibilidad en interacción con factores medioambientales. Las guías de diagnóstico para la AD incluyen evaluaciones psicológicas, psiquiátricas y neurológicas con función cerebral, y no incluyen estudios de la función visual como parte del protocolo diagnóstico, siendo fuerte la evidencia de cambios oculares en retina y en algunas funciones visuales que aparecen aun sin el deterioro cognitivo característico de esta enfermedad. Objetivo: Describir las características cognitivas y oculares en la enfermedad de Alzheimer. Metodología: Se realizó una revisión documental de literatura científica en las bases de datos PubMed, Science Direct, Hinari y Ebsco Ebsco, Proquest, entre otras, con un periodo de búsqueda de los últimos 10 años, mediante los términos mesh "Alzheimer Disease and ocular changes", "visual cognitive alteration in Alzheimer" "retina and alzheimer disease". Resultados: La AD presenta un proceso neurodegenerativo con deterioro cognitivo, que se presenta en todas las regiones de la corteza cerebral, iniciándose en corteza del hipocampo y amígdala cerebral desde donde progresa a la circunvolución para-hipocampal, lóbulos temporales y frontales. Conclusiones: Varios estudios han demostrado que la AD presenta alteraciones en memoria, lenguaje, orientación visoespacial, acompañada por cambios estructurales en cerebro y en la retina al reducir el espesor de las células ganglionares, de las capas de fibras nerviosas y al contener cuerpos de inclusión con proteína beta amiloide (Aβ) y demuestran además que el diagnóstico de alteraciones funcionales por la acumulación de Aβ es un marcador precoz de la AD.

Abstract Alzheimer's disease / AD is a progressive neurodegenerative disorder that affects memory and all cognitive functions with a late or early onset age, and occurs with a very low frequency due to genetic causes due to alteration in the PPA gene.,PS1 or PS2. The largest known etiological element is genetic, with multiple susceptibility factors in interaction with environmental factors. Diagnostic guidelines for AD include psychological, psychiatric and neurological evaluations with brain function, and do not include studies of visual function as part of the diagnostic protocol, with strong evidence of ocular changes in the retina and in some visual functions that appear even without the cognitive deterioration characteristic of this disease. Objective: To describe the cognitive and ocular characteristics in Alzheimer's disease. Methodology: A documentary review of scientific literature was made in the databases PubMed, Science Direct, Hinari and Ebsco Ebsco, Proquest, among others, with a search period of the last 10 years, through the terms mesh "Alzheimer Disease and ocular changes "," visual cognitive alteration in Alzheimer "" retina and alzheimer disease". Results: AD presents a neurodegenerative process with cognitive deterioration, which occurs in all regions of the cerebral cortex, beginning in the cortex of the hippocampus and cerebral tonsil where it progresses to the para-hippocampal gyrus, temporal and frontal lobes. Conclusions: Several studies have shown that AD presents alterations in memory, language, visuospatial orientation, accompanied by structural changes in brain and retina by reducing the thickness of ganglion cells, the layers of nerve fibers and containing inclusion bodies with protein beta amyloid (Aβ) and further demonstrate that the diagnosis of functional alterations due to the accumulation of Aβ is an early marker of AD.

Role of amyloid β in age - related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

·Age-related macular degeneration (AMD) is one of the major irreversible blinding disease affecting in nearly 50 million individuals globally. The pathogenesis and prevention of AMD has become research focus for several years. Amyloid β ( Aβ ), formed by hydrolysis of the precursor protein, is synthesized and secreted in retinal ganglion cells ( RGCs ) and retinal pigment epithelium ( RPE ) monolayer. Normally, the formation and degradation of Aβ maintain a dynamic equilibrium. When the balance was damaged, Aβ can deposit in retina which not only constitute the main components of drusen but activate complement system and induce inflammation in local tissue. Here, we review the most recent findings supporting the hypothesis that Aβ could be a key factor in AMD which may offer a better understanding of disease mechanism and develop new strategies affecting the pathogenesis.

Changes in retinal structure and function of Alzheimer's patients / 国际眼科杂志(Guoji Yanke Zazhi)

Alzheimer's disease( AD) , a neurodegenerative disease, can result in memory loss, cognitive and behavioral deficits. The pathological hallmarkes are β amyloid plaques and neurofibrillary tangles which lead loss of neurons in brain. As the extension of the central nervous system, retina has a similar tissue anatomy with central nervous system. The β amyloid plaques have also been detected in retina of AD. Furthermore, according to eye examinations of AD patients, we have found the loss of retinal ganglion cells, the attenuation of retinal nerve fiber layer thickness, the smaller changes of macula lutea, the decline of vascular density and so on. And then, there occurs the visual field loss and the decline of contrast sensitivity and so on in AD patients. Thus, the retina has occurred nerve degenerative changes in AD. Meanwhile, there has been proved that the retina nerve degeneration is even earlier than senile plaques formation in brain. In addition, curcumin, a natural and safe fluorescent dye, can be used to label β amyloid plaques in retina. The above suggests that retina can be a window for the early diagnosis of AD.

Detection of the retina degeneration in the early stage of Alzheimer's disease by spectral domain optical coherence tomography / 实用医学杂志

Objective To evaluate the applicability and reliability of optical coherence tomography (OCT) technical in detecting the thickness changes of ganglion cell complex (GCC) and outer retinal layers (ORL) in Alzheimer's disease.Method 28 AD patients and 30 healthy control subjects were recruited.SD-OCT was used to measure the macular ganglion cell complex thickness and outer retinal thickness.Cognitive function was evaluated by Mini-Mental State examination (MMSE).Intra-ocular tension and axis length were measured at the same time.Results OCT data shows statistic difference of ganglion cell complex thickness between AD group and control group,while there is no significant difference of outer retinal layers thickness between the two groups.Significant correlations between GCC thickness and MMSE scores were observed.There was no significant correlation between the MMSE scores and the ocular tension.Conclusions Retinal thickness reduction of AD patients can be detected by OTC,and could be related with disease progression.OCT can be used to screen the early stage AD patient.