Retinal Oximetry Imaging in Alzheimer’s Disease

Einarsdóttir, Anna Bryndís; Hardarson, Sveinn Hákon; Kristjánsdóttir, Jóna Valgerður; Bragason, David; Snædal, Jón; Stefánsson, Einar

doi:10.3233/jad-150457

Cited by 74 publications

(61 citation statements)

References 22 publications

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“…The use of spectrophotometric retinal oximetry measures oxygen saturation in blood vessels. Another study has confirmed that the retinal oxygen saturation in retinal arterioles and venules is significantly elevated (Einarsdottir et al 2015). Oxygen delivery is the product of the blood flow and the arteriovenous difference in oxygen concentration.…”

mentioning

confidence: 56%

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Mahajan

Votruba

2017

Acta Ophthalmologica

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Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of senile dementia. It impairs the quality of life of a person and their family, posing a serious economic and social threat in developed countries. The fact that the diagnosis can only be definitively made post‐mortem, or when the disease is fairly advanced, presents a serious problem if novel therapeutic interventions are to be devised and used early in the course of the disease. There is therefore a pressing need for more sensitive and specific diagnostic tests with which we can detect AD in the preclinical stage. The tau proteins and beta‐amyloid proteins start to accumulate 20 years before the symptoms begin to manifest. Detecting them in the preclinical stage would be a potential breakthrough in the management of AD. A high degree of clinical suspicion is needed to correlate problems in cognition with the changes in the eye, particularly the retina, pupil and ocular movements, so that the disease can be detected early and managed in the prodromal phase. In this systematic review, we ask the question whether the retina can be used to make a specific and early diagnosis of AD.

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mentioning

confidence: 56%

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Mahajan

Votruba

2017

Acta Ophthalmologica

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“…These changes include narrowed veins, reduction of blood flow, vascular attenuation, increased width variation, reduction of branching complexity and optimality, smaller fractal dimensions, and changes in tortuosity [19, 32, 50, 59, 183]. A recent study by Einarsdottir et al [49] reported that although vascular diameter was not changed, blood oxygen saturation was notably elevated in the AD retina with oximetry data closely matching that seen in AMD.…”

Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 98%

“…Reports have indicated supranuclear and deep cortical cataracts, opacity due to increased light scattering, and other changes that may be associated with the findings of Aβ peptides in the lens [49, 69, 101, 102, 133]. On the other hand, a study that examined amyloidopathy in cortical cataracts was unable to detect Aβ in lenses of patients with and without AD [132].…”

Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 99%

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer’s disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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“…A significant 2.1-fold increase in retinal amyloid index (RAI), a quantitative measure developed to assess numerical value of amyloid burden in the retina of living patients, was revealed in AD patients versus matched controls (Figure 7L–M) [485]. Recent studies applying non-invasive retinal imaging in live AD patients, which detected NFL thinning [466, 477], increased inclusion bodies [554, 555], reduced blood flow, microvasculature alterations, and oxygen saturation in arterioles and venules [479, 556, 557], and importantly, hallmark Aβ deposits [485], are encouraging first steps towards the development of practical tools for predicting disease risk and progression. Since the retina in other ND such as multiple sclerosis, ischemic stroke, and Parkinson’s disease also exhibits pathophysiological processes similar to those detected in the brain [501, 558–561], retinal imaging may also facilitate differential diagnosis for different proteinopathies, neurodegenerative and neurological diseases.…”

Section: Contribution and Role Of Retinal Imagingmentioning

confidence: 99%

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

Hampel

Toschi

Babiloni

et al. 2018

JAD

126

113

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The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

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Retinal Oximetry Imaging in Alzheimer’s Disease

Cited by 74 publications

References 22 publications

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Ocular indicators of Alzheimer’s: exploring disease in the retina

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

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