Visual Abnormalities Associate With Hippocampus in Mild Cognitive Impairment and Early Alzheimer's Disease

Zhao, Aonan; Fang, Fang; Li, Binyin; Chen, Yan; Qiu, Yinghui; Wu, Yichu; Xu, Wei; Deng, Yulei

doi:10.3389/fnagi.2020.597491

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…However, the hippocampus (HP), a key cortical structure regulating cognitive processes such as learning and memory (Broadbent et al, 2004 ; Kumaran and Maguire, 2005 ; Hannula et al, 2013 ) also resulted affected in BBSOAS patients. Due to the central role of the HP in controlling key cognitive skills, even small developmental defects can have a dramatic impact on behavioral performances (Mátéffyová et al, 2006 ; Ramos, 2008 ; Wan et al, 2021 ; Zhao et al, 2021 ). While the dorsal hippocampal pole is more involved in spatial navigation (Moser et al, 1995 ), the ventral one controls non-spatial learning and emotional behaviors (Kheirbek et al, 2013 ; Wang et al, 2013 ).…”

Section: Beyond the Neocortex: Nr2f1 Regulates The Anatomical And Functional Development Of The Hippocampusmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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The assembly and maturation of the mammalian brain result from an intricate cascade of highly coordinated developmental events, such as cell proliferation, migration, and differentiation. Any impairment of this delicate multi-factorial process can lead to complex neurodevelopmental diseases, sharing common pathogenic mechanisms and molecular pathways resulting in multiple clinical signs. A recently described monogenic neurodevelopmental syndrome named Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is caused by NR2F1 haploinsufficiency. The NR2F1 gene, coding for a transcriptional regulator belonging to the steroid/thyroid hormone receptor superfamily, is known to play key roles in several brain developmental processes, from proliferation and differentiation of neural progenitors to migration and identity acquisition of neocortical neurons. In a clinical context, the disruption of these cellular processes could underlie the pathogenesis of several symptoms affecting BBSOAS patients, such as intellectual disability, visual impairment, epilepsy, and autistic traits. In this review, we will introduce NR2F1 protein structure, molecular functioning, and expression profile in the developing mouse brain. Then, we will focus on Nr2f1 several functions during cortical development, from neocortical area and cell-type specification to maturation of network activity, hippocampal development governing learning behaviors, assembly of the visual system, and finally establishment of cortico-spinal descending tracts regulating motor execution. Whenever possible, we will link experimental findings in animal or cellular models to corresponding features of the human pathology. Finally, we will highlight some of the unresolved questions on the diverse functions played by Nr2f1 during brain development, in order to propose future research directions. All in all, we believe that understanding BBSOAS mechanisms will contribute to further unveiling pathophysiological mechanisms shared by several neurodevelopmental disorders and eventually lead to effective treatments.

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Section: Beyond the Neocortex: Nr2f1 Regulates The Anatomical And Functional Development Of The Hippocampusmentioning

confidence: 99%

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Tocco

Bertacchi

Studer

2021

Front. Mol. Neurosci.

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“…Zhao et al (38) found a similar relationship between perifoveal retinal thickness and TBV in patients with AD and MCI, as well as with the entorhinal cortex and hippocampus. The same authors found a relationship between hippocampal volume and macular RNFL thickness and P100 amplitude measured by VEP (39).…”

Section: Resultsmentioning

confidence: 86%

“…Although retinal changes related to brain Aβ deposition have been documented using PET/CT (4), most of the studies used MRI. A relationship between the retinal structure and decreased brain volume has been reported for TBV (34,37,38) and the volume of particularly vulnerable regions, such as the hippocampus (38,39), entorhinal cortex (38), and parietal lobe (34). Regarding the relationship between the retina and brain visual pathways, an increment in WM hyperintensities has been reported in the occipital lobe (12), with a higher Aβ burden in V1 (3) and on DTI (40).…”

Section: Discussionmentioning

confidence: 96%

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review

Carazo-Barrios¹,

Cabrera-Maestre²,

Alba‐Linero³

et al. 2022

Journal of Neuro-Ophthalmology

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Background:Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD.Methods:This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies.Results:Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders.Conclusions:More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.

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“…Different authors have reported reduced m-RNFL thickness in AD and MCI patients, associated with smaller hippocampal volumes and worse cognitive scores [ 50 ]. A delay in the latency time of the rod-cone response in the retina of both MCI and AD patients has also been found [ 50 ]. The presence of APOE ɛ4 in mice also induces both structural and functional retinal impairments [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Early visual alterations in individuals at-risk of Alzheimer’s disease: a multidisciplinary approach

et al. 2023

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Background The earliest pathological features of Alzheimer’s disease (AD) appear decades before the clinical symptoms. The pathology affects the brain and the eye, leading to retinal structural changes and functional visual alterations. Healthy individuals at high risk of developing AD present alterations in these ophthalmological measures, as well as in resting-state electrophysiological activity. However, it is unknown whether the ophthalmological alterations are related to the visual-related electrophysiological activity. Elucidating this relationship is paramount to understand the mechanisms underlying the early deterioration of the system and an important step in assessing the suitability of these measures as early biomarkers of disease. Methods In total, 144 healthy subjects: 105 with family history of AD and 39 without, underwent ophthalmologic analysis, magnetoencephalography recording, and genotyping. A subdivision was made to compare groups with less demographic and more risk differences: 28 high-risk subjects (relatives/APOEɛ4 +) and 16 low-risk (non-relatives/APOEɛ4 −). Differences in visual acuity, contrast sensitivity, and macular thickness were evaluated. Correlations between each variable and visual-related electrophysiological measures (M100 latency and time–frequency power) were calculated for each group. Results High-risk groups showed increased visual acuity. Visual acuity was also related to a lower M100 latency and a greater power time–frequency cluster in the high-risk group. Low-risk groups did not show this relationship. High-risk groups presented trends towards a greater contrast sensitivity that did not remain significant after correction for multiple comparisons. The highest-risk group showed trends towards the thinning of the inner plexiform and inner nuclear layers that did not remain significant after correction. The correlation between contrast sensitivity and macular thickness, and the electrophysiological measures were not significant after correction. The difference between the high- and low- risk groups correlations was no significant. Conclusions To our knowledge, this paper is the first of its kind, assessing the relationship between ophthalmological and electrophysiological measures in healthy subjects at distinct levels of risk of AD. The results are novel and unexpected, showing an increase in visual acuity among high-risk subjects, who also exhibit a relationship between this measure and visual-related electrophysiological activity. These results have not been previously explored and could constitute a useful object of research as biomarkers for early detection and the evaluation of potential interventions’ effectiveness.

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Visual Abnormalities Associate With Hippocampus in Mild Cognitive Impairment and Early Alzheimer's Disease

Cited by 22 publications

References 42 publications

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review

Early visual alterations in individuals at-risk of Alzheimer’s disease: a multidisciplinary approach

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