Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

Paquet, Claire; Boissonnot, M; Roger, Florent; Dighiero, P.; Gil, Roger; Hugon, Jacques

doi:10.1016/j.neulet.2007.02.090

Cited by 311 publications

(314 citation statements)

References 21 publications

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“…In vivo studies with optical coherence tomography (OCT) corroborated these findings, showing a reduction of the retinal nerve fiber layer (RNFL) thickness in AD patients 12, 13, 14, 15, 16, 17, 18, 19, 20. Accumulation of Aβ in the retina of AD patients has also been reported in a few studies.…”

mentioning

confidence: 60%

Melanopsin retinal ganglion cell loss in Alzheimer disease

Morgia

Ross‐Cisneros

Koronyo

et al. 2015

Annals of Neurology

320

397

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ObjectiveMelanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.MethodsWe assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls.ResultsWe demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs.InterpretationWe show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109

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mentioning

confidence: 60%

Melanopsin retinal ganglion cell loss in Alzheimer disease

Morgia

Ross‐Cisneros

Koronyo

et al. 2015

Annals of Neurology

320

397

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“…Later noninvasive studies of RNFL and ONH using scanning laser ophthalmoscopy (SLO) [42], and time-domain OCT (TD-OCT) studies confirmed the reduction in peripapillary RNFL thickness [40,[43][44][45][46][47]. In addition, invivo studies have shown reduced macular thickness and volume in patients with AD [44,[48][49][50][51][52][53][54].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 91%

“…TD-OCT has been the most widely employed ocular imaging technique for assessment of optic nerve degeneration in AD [43][44][45][46][47], as well as for evaluating macular thinning in these patients [44].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…While most OCT studies did not show correlation between Minimal Mental State Examination (MMSE) and peripapillary RNFL thinning (Table 2), one TD-OCT study reported correlation between MMSE scores and macular volume [44], and more recent studies using SD-OCT have indeed reported a significant correlation between MMSE scores and RNFL thickness [50,66,72,76,77]. Studies comparing changes in RNFLT in MCI and AD (Table 2) have also yielded conflicting results, although the majority reported no statistically significant differences between MCI and AD patient groups [46,47,54,77]. The metaanalyses by K.L.…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

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Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Cunha

Moura-Coelho

Proença

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on invivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.

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“…This change in protein levels is similar to that observed in the CSF in AD. Given the retinal degeneration observed in AD [119][120][121][122][123] and the recently reported common features between AD and glaucoma [61,107,[121][122][123][124][125][126][127][128][129][130], the vitreous humor is an interesting focus for future research into ocular protein changes in AD.…”

Section: (Figure 3)mentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

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Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a progressive decline in memory, learning and executive function and neuropathologically by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive pre-mortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred, hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments.While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular based screening test for AD.

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Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

Cited by 311 publications

References 21 publications

Melanopsin retinal ganglion cell loss in Alzheimer disease

Melanopsin retinal ganglion cell loss in Alzheimer disease

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Ocular Biomarkers for Early Detection of Alzheimer's Disease

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