Relationship between Cognitive Impairment and Retinal Morphological and Visual Functional Abnormalities in Alzheimer Disease

İşeri, Pervin; Altinaş, Ozgül; Tokay, Tomris; Yüksel, Nurşen

doi:10.1097/01.wno.0000204645.56873.26

Cited by 357 publications

(362 citation statements)

References 32 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

306

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

306

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%

“…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: 99%

“…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%

“…Whether or not a correlation exists between retinal changes and severity of dementia also remains a controversial issue. 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].…”

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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Association of Retinal Changes With Alzheimer Disease Neuroimaging Biomarkers in Cognitively Normal Individuals

Byun

Park

Lee³

et al. 2021

JAMA Ophthalmol

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IMPORTANCERetinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD.OBJECTIVES To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD.

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Relationship between Cognitive Impairment and Retinal Morphological and Visual Functional Abnormalities in Alzheimer Disease

Abstract: Our study confirms some other studies in showing that in AD patients there is a reduction of parapapillary and macular RNFL thickness and macular volume as measured by OCT. The reduction in macular volume was related to the severity of cognitive impairment.

Cited by 357 publications

References 32 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

Association of Retinal Changes With Alzheimer Disease Neuroimaging Biomarkers in Cognitively Normal Individuals

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