Cholinergic supersensitivity of the iris in Alzheimer's disease.

Idiáquez, Juan; Alvarez, GG; Villagra, Roque; Martin, Richard A.

doi:10.1136/jnnp.57.12.1544-a

Cited by 34 publications

(14 citation statements)

References 8 publications

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“…69,70 The main ocular biomarker investigated for AD has been thinning of the RNFL, as this may reflect both generalised neurodegeneration and local involvement, and this is reviewed below. Other ocular biomarkers investigated in AD include pupillary abnormalities: hypersensitivity to pupillary dilatation with cholinergic antagonist eye drops, 71-73 supersensitive pupillary response to cholinergic agonists, 74 and altered pupil flash responses. 75,76 AB deposition (AB 1-40 and AB 1-42) has been found in the lens with comparable concentrations to those in the brain.…”

Section: The Eye In Admentioning

confidence: 99%

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Jones-Odeh

Hammond

2015

Eye

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Glaucoma is a neurodegenerative disorder with established relationships with ocular structures such as the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). Ocular imaging techniques such as optical coherence tomography (OCT) allow for quantitative measurement of these structures. OCT has been used in the monitoring of glaucoma, as well as investigating other neurodegenerative conditions such as Alzheimer's disease (AD) and multiple sclerosis (MS). In this review, we highlight the association between these disorders and ocular structures (RNFL and GCL), examining their usefulness as biomarkers of neurodegeneration. The average RNFL thickness loss in patients with AD is 11 μm, and 7 μm in MS patients. Most of the studies investigating these changes are cross-sectional. Further longitudinal studies are required to assess sensitivity and specificity of these potential ocular biomarkers to neurodegenerative disease progression. Eye (2015Eye ( ) 29, 1270Eye ( -1284 doi:10.1038/eye.2015; published online 4 September 2015 IntroductionGlaucoma is a neurodegenerative optic neuropathy manifesting with progressive retinal ganglion cell (RGC) and axonal loss, which can result in visual field defects and blindness because of permanent cellular and neuronal damage. Subjective clinical examination of the optic nerve head (ONH) allows for assessment and monitoring of the structural changes associated with glaucoma. However, objective detection of defects in the peripapillary retinal nerve fibre layer (RNFL) by ophthalmoscopy is difficult. The relationship between glaucoma progression and the structural changes observed at the ONH, RGC layer, and RNFL in glaucoma is well established. [1][2][3][4] Early diagnosis and treatment of glaucoma is vital to maintain visual field, as loss of RGCs is irreversible, 5 and even before any detectable visual field defects, there is a substantial loss of RGCs. Morphological abnormalities can develop 3-5 years before any functional loss is detected. 6 Since the introduction of ocular imaging techniques such as optical coherence tomography (OCT), peripapillary RNFL thickness measurements have been used for the detection and monitoring of glaucoma. 7,8 However, the use of OCT has extended beyond RNFL measurements for glaucoma, and has also been used in the investigation of other neurodegenerative disorders such as Alzheimer's disease (AD) 9-11 and multiple sclerosis (MS). [12][13][14] In addition, given the similarities of brain and retinal foetal angiogenesis, 15,16 retinal microvasculature has also been investigated as a biomarker of changes in cerebral vasculature and cognitive decline. [17][18][19] In this review, we examine the relationships between glaucoma, neurodegenerative disease, and cognitive impairment, and the use of RNFL thickness and RGC loss as potential ocular biomarkers for neurodegenerative disorders such as AD and MS. We review the strength of associations between RNFL and RGC and Eye (2015Eye ( ) 29, 1270Eye ( -1284Eye ( © 2015 Macmillan Publis...

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Section: The Eye In Admentioning

confidence: 99%

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Jones-Odeh

Hammond

2015

Eye

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“…However, apart from alterations in the central visual regions, specific pathological changes have been reported in the eye. Ocular abnormalities that have been reported to accompany AD include: enhanced pupil response to cholinergic drops,26 27 altered pupil flash response,28 Aβ proteins which have also been found to exist in the lens (both, Aβ-40 and Aβ-42), aqueous humour (Aβ-40) and vitreous humour (Aβ-42) 29 30. However, the exact link between the presence of Aβ proteins in these tissues and AD remains to be determined.…”

Section: Visual and Ocular Abnormalities In Alzheimer's Diseasementioning

confidence: 99%

Retinal pathology as biomarker for cognitive impairment and Alzheimer's disease

Ikram

Cheung

Wong

et al. 2012

J Neurol Neurosurg Psychiatry

101

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Alzheimer's disease (AD) is the most common cause of dementia. Furthermore, over the last few decades, there has been a shift towards identifying earlier stages of AD, which include mild cognitive impairment (MCI). Improved methods of screening and early detection are essential to identify cognitively normal individuals who have a high risk of developing MCI and AD, so that interventions can be developed to delay the progression of specific disease-related pathologies. Thus far, novel biomarkers that have been examined include structural and functional neuroimaging as well as biochemical analysis of cerebrospinal fluid. However, in spite of these efforts, there is still an urgent need for unravelling additional novel biomarkers for AD and MCI. As the retina shares many features with the brain, including embryological origin, anatomical (such as microvascular bed) and physiological characteristics (such as blood-tissue barrier), it has been suggested that the retina may provide an easily accessible and non-invasive way of examining pathology in the brain. While most AD-related pathology occurs in the brain, the disease has also been reported to affect different regions of the retina, including the macular region and optic disc. Studies have suggested that retinal pathology, such as deposits in the macular region, decreased retinal nerve fibre thickness, and optic disc cupping and retinal microvascular abnormalities may be related to AD and cognitive impairment. This article presents a review of current literature on retinal involvement in AD and MCI.

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“…A hypersensitive pupil response to a cholinergic agonist (pilocarpine -contraction) or antagonist (tropicamide -dilation) has been reported in AD patients [69][70][71][72][73][74][75][76][77][78]. The neurotransmitter acetylcholine is deficient in the AD brain [67,79], hence cholinergic dysfunction in iris nerve cells is a possible explanation for the hypersensitive response, although in this case one would expect to find agonist hypersensitivity with antagonist subsensitivity, or vice versa.…”

Section: (Figure 2)mentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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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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Cholinergic supersensitivity of the iris in Alzheimer's disease.

Cited by 34 publications

References 8 publications

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Retinal pathology as biomarker for cognitive impairment and Alzheimer's disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

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