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      Visual contrast sensitivity is associated with the presence of cerebral amyloid and tau deposition

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          Abstract

          Visual deficits are common in neurodegenerative diseases including Alzheimer’s disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer’s disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer’s disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer’s disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with [ 18F]flortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer’s disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer’s disease-related pathology in older adults at risk for cognitive decline.

          Abstract

          Poorer visual contrast sensitivity was associated with greater cerebral amyloid and tau in individuals with or at risk for Alzheimer’s disease. Visual contrast sensitivity accurately predicted the presence of cerebral amyloid or tau. Visual contrast sensitivity has potential as a non-invasive screening tool to detect Alzheimer’s pathophysiology in at-risk individuals.

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          Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set (UDS)

          Introduction: The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0. Methods: The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed. Results: Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online. Discussion: The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia.
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            Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer’s disease in the 3xTg-AD mouse model

            Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10–15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models. Retina can be considered a simple model of the brain, as some pathological changes and therapeutic strategies from the brain may be observed or applicable to the retina. Here we propose new retinal biomarkers that could anticipate the AD diagnosis and help the beginning and the follow-up of possible future treatments. We analyzed retinal tissue of triple-transgenic AD mouse model (3xTg-AD) for the presence of pathological hallmarks during disease progression. We found the presence of amyloid beta plaques, tau tangles, neurodegeneration, and astrogliosis in the retinal ganglion cell layer of 3xTg-AD mice, already at pre-symptomatic stage. Moreover, retinal microglia in pre-symptomatic mice showed a ramified, anti-inflammatory phenotype which, during disease progression, switches to a pro-inflammatory, less ramified one, becoming neurotoxic. We hypothesize retina as a window through which monitor AD-related neurodegeneration process.
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              Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale

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                Author and article information

                Contributors
                Journal
                Brain Commun
                Brain Commun
                braincomms
                Brain Communications
                Oxford University Press
                2632-1297
                2020
                26 February 2020
                26 February 2020
                : 2
                : 1
                : fcaa019
                Affiliations
                [f1 ] Department of Radiology and Imaging Sciences, Indiana University School of Medicine , Indianapolis, IN, USA
                [f2 ] Indiana Alzheimer Disease Center, Indiana University School of Medicine , Indianapolis, IN, USA
                [f3 ] Department of Ophthalmology, UF College of Medicine—Jacksonville , Jacksonville, FL, USA
                [f4 ] Department of Biostatistics, Indiana University School of Medicine , Indianapolis, IN, USA
                [f5 ] Department of Neurology, Indiana University School of Medicine, Indianapolis , IN, USA
                Author notes
                Correspondence to: Shannon L. Risacher, PhD Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer Disease Center, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA E-mail: srisache@ 123456iupui.edu
                Article
                fcaa019
                10.1093/braincomms/fcaa019
                7151662
                32309804
                1222ad03-13aa-4401-b840-bb5bdaf9d5ba
                © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 16 September 2019
                : 07 December 2019
                : 20 February 2020
                Page count
                Pages: 14
                Funding
                Funded by: National Institute on Aging, DOI 10.13039/100000049;
                Award ID: K01 AG049050
                Award ID: R01 AG061788
                Award ID: R01 AG19771
                Award ID: P30 AG10133
                Funded by: Alzheimer’s Association;
                Funded by: Indiana University Health-Indiana University School of Medicine Strategic Research Initiative;
                Funded by: Indiana Clinical and Translational Sciences Institute (CTSI);
                Funded by: Indiana University Pervasive Technology Institute;
                Funded by: Lilly Endowment, DOI 10.13039/100006976;
                Funded by: National Science Foundation, DOI 10.13039/100000001;
                Award ID: CNS-0521433
                Categories
                Original Article

                vision,alzheimer’s disease,amyloid,tau,mild cognitive impairment

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