Tropicamide Eyedrops Cannot Be Used for Reliable Diagnosis of Alzheimer's Disease

Graff‐Radford, Neill R.; Lin, Siong-Chi; Brazis, Paul W.; Bolling, James P.; Liesegang, Thomas J.; Lucas, John A.; Uitti, Ryan J.; O’Brien, Peter C.

doi:10.4065/72.6.495

Cited by 28 publications

(10 citation statements)

References 13 publications

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“…In addition, the literature regarding the visual changes in AD is controversial, with different studies often giving conflicting results. In addition, optometrists should not use the 0.01% tropicamide test as a test for AD, as recent studies 57,58 have not confirmed earlier reports. 53 However, it is important that optometrists continue to use the regular dosage of tropicamide (1%) for papillary dilation and ocular health examination.…”

Section: In the Identification Of Admentioning

confidence: 90%

“…55 Hence, use of the tropicamide response cannot be recommended as a clinical application to detect AD. 57,58 Enhanced pupillary responses in AD have also been reported following the application of dilute solutions of phenylephrine (a sympathetic agonist) and of pilocarpine (a cholinergic agonist). 59 Reductions in the pupillary light reflex have also been reported in AD, although these responses are highly variable.…”

Section: Pupillary Functionmentioning

confidence: 98%

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Alzheimer's Disease and the Eye☆

Armstrong

2009

Journal of Optometry

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Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. RESUMENLas distintas formas de demencia, entre las que se incluye la enfermedad de Alzheimer (EA), son graves trastornos que causan problemas visuales en las personas de edad avanzada. La patología de la EA incluye la acumulación en el cerebro del péptido β-amiloide (Aβ en forma de placas seniles (PS) y de proteína tau anormalmente fosforilada en forma de ovillos neurofibrilares (ONF). Se ha documentado un amplio espectro de problemas visuales en pacientes con EA, entre los que se incluye la pérdida de agudeza visual (AV), problemas relacionados con la visión de color y el campo visual, cambios en la respuesta pupilar ante midriáticos, problemas de fijación así como movimientos oculares sacádicos y de seguimiento anormales; cambios en la sensibilidad al contraste y en los potenciales evocados visuales (PEV); y alteraciones de algunas funciones visuales complejas, tales como la lectura, la función visuoespacial, y a la hora de nombrar y de identificar objetos. Muchos de estos cambios no están exentos de cierta controversia, puesto que en la literatura aparecen datos contradictorios al respecto y, además, no hay ninguna característica visual u ocular en la que se pueda basar el diagnóstico de la EA. Además, se ha observado que algunos de los cambios patológicos que aparecen en la EA afectan al ojo, a la vía óptica y al córtex visual. El optometrista juega un papel destacado a la hora de ayudar a los pacientes que padecen EA. Si se sospecha que existen signos y síntomas de la enfermedad, la ayuda en la optimización de la función visual contribuirá para mejorar su calidad de vida. INTRODUCTIONA significant part of current optometric practice is directed to the visual problems of the elderly and this trend is likely to continue, given the demographic increase in the geriatric ...

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Section: In the Identification Of Admentioning

confidence: 90%

Section: Pupillary Functionmentioning

confidence: 98%

Alzheimer's Disease and the Eye☆

Armstrong

2009

Journal of Optometry

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“…Following the publication of the original report of pupillary sensitivity in patients with a diagnosis of probable AD, some 27 publications have appeared evaluating the use of the pupil assay as an early biomarker for AD. These reports Buque et al 1997;Feiler et al 1996;Ferrario et al 1998;FitzSimon et al 1997;Fridh et al 1996;Gomes-Tortosa et al 1996;Graff-Radford et al 1997;Growdon et al 1997;Higuchi et al 1997a;Imamura et al 1996;Kalman et al 1997;Kaneyuki et al 1998;Kono et al 1996;Kurz et al 1997;Leszek et al 1996;Litvan & FitzGibbon 1996;Loupe et al 1996;Marx et al 1995;Matsushita et al 1996;Nuzzi et al 1996;Reitner et al 1997;Robles et al 1996, Schweitzer et al 1996Tourino et al 1997;Treloar et al 1996;Woodruf-Pak et al 1996) confirmed, with rare exceptions, that patients with a diagnosis of probable AD exhibited an exaggerated response to tropicamide. However, a number of these studies had shown varying degrees of overlap in the response of AD patients and community dwelling elder controls.…”

Section: Discussionmentioning

confidence: 94%

ApoE allelic variability influences pupil response to cholinergic challenge and cognitive impairment

Scinto

2006

Genes Brain and Behavior

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Exaggerated pupil response to dilute tropicamide has been suggested as an early biological marker for Alzheimer’s disease. The current study links apolipoprotein E (ApoE) allelic variability to the magnitude of pupil response in a sample of community‐dwelling elderly without a diagnosis of Alzheimer’s disease or dementia. Possession of an ɛ4 allele influences both the likelihood of exhibiting an exaggerated pupil response above a predetermined cut‐off (13% above baseline diameter) and the absolute overall magnitude of the response. Allelic variability was also shown to correlate with cognitive impairments in memory and attention. The data in this study further elucidate the nature of the biological bond between an exaggerated pupil response and the pathology of Alzheimer’s disease. ApoE allelic variability is probably linked to pupil response through its influence on tau hyperphosphorylation. The early Alzheimer’s pathology seen in the Edinger–Westphal area of cranial nerve III, a major centre for pupil control, is primarily tau‐based with significant cell loss in this nucleus leading to central denervation hypersensitivity even in elderly who are clinically silent but who have early pathology.

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“…In 1994, Scinto et al reported that AD patients had hypersensitivity of the pupil dilation after diluted tropicamide instillation [282]. Since the publication of this work, numerous studies have been performed, with several results showing both negative [283][284][285][286][287][288][289][290][291] and positive results [281,282,[292][293][294][295][296][297]. Some of these studies point to a lack of specificity to the pupil tropicamide test in AD [288,298].…”

Section: Pupillary Response To Lightmentioning

confidence: 90%

The Impact of the Eye in Dementia: The Eye and its Role in Diagnosis and Follow‐up

Salobrar‐García¹,

Ramírez²,

Hoz³

et al. 2016

Update on Dementia

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Over the last few decades, the importance of ophthalmic examination in neurodegenerative diseases of the CNS has reportedly increased. The retina is an extension of the CNS and thus should not be surprising to find abnormal results in both the test exploring visual processing and those examining the retina of patients with CNS degeneration. Current in vivo imaging techniques are allowing ophthalmologists to detect and quantify data consistent with the histopathological findings described in the retinas of Alzheimer's disease (AD) patients and may help to reveal unsuspected retinal and opticnerve repercussions of other CNS diseases. In this chapter, we perform an analysis of the physiological changes in ocular and cerebral ageing. We analyse the ocular manifestations in CNS disorders such as stroke, AD and Parkinson's disease. In addition, the pathophysiology of both the eye and the visual pathway in AD are described. The value of the visual psychophysical tests in AD diagnosis is reviewed as well as the main findings of the optical coherence tomography as a contribution to the diagnosis and monitoring of the disease. Finally, we examine the association of two neurodegenerative diseases, AD and glaucoma, as mere coincidence or possible role in the progression of the neurodegeneration.Diagnosis and follow-up of AD, especially the early-onset cases, become difficult, due to imprecise neuropsychological testing, sophisticated but expensive neuroimaging techniques, and invasive sampling of cerebrospinal fluid [31,32]. OCT is a reliable noninvasive technique, routinely used in ophthalmology to visualise and quantify the layers of the retina. This technique enables quantitative cross-sectional imaging of the RNFL and macular volume. As a measure of neuronal degeneration, changes in longitudinal OCT measurements of the RNFL can act as a surrogate marker of axonal health. Thus, OCT could become an invaluable tool for measuring axonal loss, as a biomarker, in different neurological conditions [33,[51][52][53][54][55][56][57][58][59][60][61] (Figure 1).In a review of a meta-analysis which investigates the role of OCT in detecting RNFL thinning in AD patients, it was found that the OCT is a well-suited paraclinical methodology to assess RNFL thickness in both AD and mild cognitive impairment (MCI) disorders [19]. Macular studies in AD using OCT have recently reported that mild AD patients with a high average score (23.3 ± 3.1) on the Mini-Mental State Examination (MMSE) had significantly reduced macular nerve-fibre-layer thickness with or without significant peripapillary involvement [19,40,62,63]. OCT thus offers the clinician a fast, reliable, reproducible, noninvasive method to evaluate and monitor several neurological diseases [64]. Search strategy and selection criteriaA literature search was performed up to April 2016 using the MEDLINE database, PubMed and Google Scholar search services with the following key words and word combinations: dementia, Alzheimer's disease, ageing, vision, eye, physiopathology, visual pathwa...

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Tropicamide Eyedrops Cannot Be Used for Reliable Diagnosis of Alzheimer's Disease

Cited by 28 publications

References 13 publications

Alzheimer's Disease and the Eye☆

Alzheimer's Disease and the Eye☆

ApoE allelic variability influences pupil response to cholinergic challenge and cognitive impairment

The Impact of the Eye in Dementia: The Eye and its Role in Diagnosis and Follow‐up

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