Visual Features in Alzheimer’s Disease: From Basic Mechanisms to Clinical Overview

Cerquera-Jaramillo, María Alejandra; Nava-Mesa, Mauricio O.; González-Reyes, Rodrigo E.; Tellez-Conti, Carlos; de-la-Torre, Alejandra

doi:10.1155/2018/2941783

Cited by 38 publications

(42 citation statements)

References 209 publications

(299 reference statements)

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“…AD is the most common cause of dementia and is characterized by cognitive decline, caused by the accumulation of extra-and intra-cellular A plaques and hyperphosphorylated tau (40,41). The studies conducted on postmortem brain tissues have revealed excessive chronic inflammation in the plaque area.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

2020

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Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range of cellular processes, including cell proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, and inflammation. Recently, several studies have highlighted the pivotal role of sphingolipids in neuroinflammatory regulation. Sphingolipids have multiple functions, including induction of the expression of various inflammatory mediators and regulation of neuroinflammation by directly effecting the cells of the central nervous system. Accumulating evidence points to sphingolipid engagement in neuroinflammatory disorders, including Alzheimer's and Parkinson's diseases. Abnormal sphingolipid alterations, which involves an increase in ceramide and a decrease in sphingosine kinase, are observed during neuroinflammatory disease. These trends are observed early during disease development, and thus highlight the potential of sphingolipids as a new therapeutic and diagnostic target for neuroinflammatory diseases. [BMB Reports 2020; 53(1): 28-34]

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Section: Alzheimer's Diseasementioning

confidence: 99%

Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

2020

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“…The most reliable and frequently used biomarkers are elevated levels of Aβ 1−42 , the most toxic form of Aβ, total tau (t-tau), and hyper-phosphorylated tau (p-tau) in the CSF [ 6 ]. Vision-related changes are common in AD [ 7 ] and are summarized in Table 1 . Some of the visual defects are due to degeneration of the visual cortex, while others are attributed to retinal degeneration associated with glaucoma and age-related macular degeneration (AMD) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is believed that chronic elevation of IOP leads to the accumulation of Aβ and p-tau in RGCs, resulting in their loss. This leads to thinning of the RNFL and optic nerve atrophy, ultimately leading to permanent blindness because of the failure to transmit visual stimuli to the brain [ 7 , 8 ]. However, it is difficult to distinguish whether visual defects due to RGC cell loss appear earlier than those due to neuronal loss in the occipital cortex, information critical for the early diagnosis of AD.…”

Section: Introductionmentioning

confidence: 99%

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Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

Ashok

Singh

Chaudhary

et al. 2020

IJMS

105

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Age-related macular degeneration (AMD) and glaucoma are degenerative conditions of the retina and a significant cause of irreversible blindness in developed countries. Alzheimer’s disease (AD), the most common dementia of the elderly, is often associated with AMD and glaucoma. The cardinal features of AD include extracellular accumulation of amyloid β (Aβ) and intracellular deposits of hyper-phosphorylated tau (p-tau). Neuroinflammation and brain iron dyshomeostasis accompany Aβ and p-tau deposits and, together, lead to progressive neuronal death and dementia. The accumulation of Aβ and iron in drusen, the hallmark of AMD, and Aβ and p-tau in retinal ganglion cells (RGC), the main retinal cell type implicated in glaucoma, and accompanying inflammation suggest overlapping pathology. Visual abnormalities are prominent in AD and are believed to develop before cognitive decline. Some are caused by degeneration of the visual cortex, while others are due to RGC loss or AMD-associated retinal degeneration. Here, we review recent information on Aβ, p-tau, chronic inflammation, and iron dyshomeostasis as common pathogenic mechanisms linking the three degenerative conditions, and iron chelation as a common therapeutic option for these disorders. Additionally discussed is the role of prion protein, infamous for prion disorders, in Aβ-mediated toxicity and, paradoxically, in neuroprotection.

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“…As such, monitoring of visual functions could identify those living with dementia who are at greater risk of injurious falls and hospitalization that could exacerbate the progression of dementia. Recent reviews have called for more research into the role of visual functions as a less costly and invasive biomarker for the progression or severity of dementia [ 28 , 29 ]. However, the interaction among primary visual function (VA and contrast sensitivity), binocular functions such as stereopsis and horizontal fusional vergence range, and rate of cognitive decline (eg, cognitive test score) in PWD is yet to be evaluated formally.…”

Section: Introductionmentioning

confidence: 99%

Binocular Vision, Visual Function, and Pupil Dynamics in People Living With Dementia and Their Relation to the Rate of Cognitive Decline and Structural Changes Within the Brain: Protocol for an Observational Study

2020

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Background Visual impairment is a common comorbidity in people living with dementia. Addressing sources of visual difficulties can have a significant impact on the quality of life for people living with dementia and their caregivers. Depth perception problems are purportedly common in dementia and also contribute to falls, visuomotor task difficulties, and poorer psychosocial well-being. However, depth perception and binocular vision are rarely assessed in dementia research. Sleep fragmentation is also common for people living with dementia, and binocular cooperation for depth perception can be affected by fatigue. Pupillary responses under cognitive load also have the potential to be a risk marker for cognitive decline in people living with dementia and can be combined with the above measures for a comprehensive evaluation of clinical visual changes in people living with dementia and their relation to changes in cognitive status, sleep quality, and cortical structure or function. Objective This study aims to characterize the nature of clinical visual changes and altered task-evoked pupillary responses that may occur in people living with dementia and evaluate whether these responses relate to changes in cognitive status (standardized Mini Mental State Examination [MMSE] score), Pittsburgh sleep quality index, and cortical structure or function. Methods This proposed exploratory observational study will enroll ≤210 people with recently diagnosed dementia (within the last 24 months). The following parameters will be assessed on 3 occasions, 4 months apart (plus or minus 2 weeks): visual function (visual acuity and contrast sensitivity), binocular function (motor fusion and stereopsis), task-evoked pupillary responses (minimum and maximum pupil size, time to maximum dilation, and dilation velocity), cognitive status (MMSE score), and sleep quality (Pittsburgh Sleep Quality Index). A subset of patients (n=30) with Alzheimer disease will undergo structural and functional magnetic resonance imaging at first and third visits, completing a 10-day consensus sleep diary to monitor sleep quality, verified by sleep actimetry. Results This research was funded in February 2018 and received National Health Service Research Ethics Committee approval in September 2018. The data collection period was from October 1, 2018, to November 30, 2019. A total of 24 participants were recruited for the study. The data analysis is complete, with results expected to be published before the end of 2020. Conclusions Findings will demonstrate how often people with dementia experience binocular vision problems. If frequent, diagnosing and treating them could improve quality of life by reducing the risk of falls and fine visuomotor task impairment and by relieving psychosocial anxiety. This research will also demonstrate whether changes in depth perception, pupillary responses, and quality of vision relate to changes in memory or sleep quality and brain structure or function. If related, these quick and noninvasive eye tests help monitor dementia. This would help justify whether binocular vision and pupillary response testing should be included in dementia-friendly eye-testing guidelines. International Registered Report Identifier (IRRID) RR1-10.2196/16089

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Visual Features in Alzheimer’s Disease: From Basic Mechanisms to Clinical Overview

Cited by 38 publications

References 209 publications

Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

Sphingolipids in neuroinflammation: a potential target for diagnosis and therapy

Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

Binocular Vision, Visual Function, and Pupil Dynamics in People Living With Dementia and Their Relation to the Rate of Cognitive Decline and Structural Changes Within the Brain: Protocol for an Observational Study

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