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      Distinguishing cognitive impairment by using singularity spectrum and lacunarity analysis of the retinal vascular network

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          Abstract.

          The development of effective therapies for cognitive impairment (CI), especially due to Alzheimer’s disease, demands diagnosing the condition during the prodromal phase. The diagnosis of CI involves expensive and invasive methods, such as positron emission tomography and cerebrospinal fluid assessment via spinal tap. Hence, a comparatively lower cost and noninvasive method of diagnosis is imperative. The human retina is an extension of the brain characterized by similarities in vascular and neural structures. The complications of CI are not only limited to the brain but also affect the retina for which the loss of retinal ganglion cells has been associated with neurodegeneration in the brain. The loss of retinal ganglion cells in individuals with CI may be related to reduced vascular demand and a potential remodeling of the retinal vascular branching complexity. Retinal imaging biomarkers may provide a low cost and noninvasive alternative for the diagnosis of CI. In this study, the retinal vascular branching complexity of patients with CI was characterized using the singularity spectrum multifractal dimension and lacunarity parameter. A reduced vascular branching complexity was observed in subjects with CI when compared to age- and sex-matched cognitively healthy controls. Significant associations were also found between retinal vascular and functional parameters.

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            Microvascular network alterations in the retina of patients with Alzheimer's disease.

            Although cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. Because the retina provides a noninvasive window to assess the microcirculation, we determined whether quantitatively measured retinal microvascular parameters are associated with AD. We conducted a case-control study (case:control matching ≈ 1:2). Retinal photographs were analyzed using a computer program, and a spectrum of quantitative retinal microvascular parameters (caliber, fractal dimension, tortuosity, and bifurcation) were measured. Logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval for AD adjusting for age, gender, ethnicity, smoking, hypertension, diabetes, hypercholesterolemia, and history of myocardial infarction. We included 136 demented patients with AD and 290 age-gender-race-matched controls. Persons with narrower venular caliber (OR per standard deviation [SD] decrease, 2.01 [1.27-3.19]), decreased arteriolar and venular fractal dimension (OR per SD decrease 1.35 [1.08-1.68], 1.47 [1.17-1.84], respectively) and increased arteriolar and venular tortuosity (OR per SD increase, 1.84 [1.40-2.31], 1.94 [1.48-2.53], respectively) were more likely to have AD. These associations still persisted when only AD cases without a history of cerebrovascular disease were included. Patients with AD have altered microvascular network in the retina (narrower retinal venules and a sparser and more tortuous retinal vessels) compared with matched nondemented controls. These changes in retinal microvasculature may reflect similar pathophysiological processes in cerebral microvasculature in the brains of patients with AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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              Is Open Access

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

              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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                Author and article information

                Journal
                Neurophotonics
                Neurophotonics
                NEUROW
                NPh
                Neurophotonics
                Society of Photo-Optical Instrumentation Engineers
                2329-423X
                2329-4248
                23 September 2019
                October 2019
                : 6
                : 4
                : 041109
                Affiliations
                [a ]University of Miami , Bascom Palmer Eye Institute, Department of Ophthalmology, Miami, Florida, United States
                [b ]Pallas Kliniken , Retinology Unit, Olten, Switzerland
                [c ]Semmelweis University , Department of Ophthalmology, Budapest, Hungary
                Author notes
                [* ]Address all correspondence to Delia Cabrera DeBuc, E-mail: dcabrera2@ 123456med.miami.edu
                Author information
                https://orcid.org/0000-0002-1577-7950
                https://orcid.org/0000-0001-6329-442X
                https://orcid.org/0000-0003-1632-9452
                Article
                NPh-19050SSR 19050SSR
                10.1117/1.NPh.6.4.041109
                6756485
                31572744
                9e07d1cc-c14e-434e-97be-915fd7eac957
                © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
                History
                : 24 May 2019
                : 27 August 2019
                Page count
                Figures: 1, Tables: 3, References: 54, Pages: 8
                Funding
                Funded by: Alzheimer’s Association https://doi.org/10.13039/100000957
                Award ID: AARGD-17-531255
                Funded by: Health Services and Delivery Research (HSDR) https://doi.org/10.13039/501100002001
                Award ID: P30-EY014801
                Funded by: Finker Frenkel Legacy Foundation
                Funded by: Research to Prevent Blindness, Inc.
                Categories
                Special Section on Advanced Retinal Imaging: Instrumentation, Methods, and Applications
                Paper
                Custom metadata
                Arthur et al.: Distinguishing cognitive impairment by using singularity spectrum…

                cognitive impairment,singularity spectrum,lacunarity,retinal vascular complexity,multifractal analysis

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