**Author details**

Elena Salobrar‐García<sup>1</sup> , Ana I. Ramírez2 , Rosa de Hoz2 , Pilar Rojas3 , Juan J. Salazar2 , Blanca Rojas1 , Raquel Yubero4 , Pedro Gil4 , Alberto Triviño1 and José M. Ramírez1\*

\*Address all correspondence to: ramirezs@med.ucm.es

1 Ramon Castroviejo Institute of Ophthalmologic Research, School of Medicine, Complutense University of Madrid (UCM), Spain

2 Ramon Castroviejo Institute of Ophthalmologic Research, School of Optics and Optomet‐ ry, Complutense University of Madrid (UCM), Spain

3 Service of Ophthalmology Hospital Gregorio Marañon, Ramon Castroviejo Institute of Ophthalmologic Research, Complutense University of Madrid (UCM), Spain

4 Service of Geriatrics, University Hospital Clinico San Carlos, Complutense University of Madrid (UCM), Spain

### **References**

This kind of excitotoxicity is caused by the excessive activation of NMDA glutamate receptors, at least partially. This excessive activity in the NMDA receptor entails an abnormally high influx of calcium ions in the neurons, which triggers multiple outcomes resulting in apoptosis. Thus, pharmacological blockage of NMDA receptor activity would prevent apoptosis related to excitotoxicity. However, the use of a neuroprotective drug (memantine) in patients with POAG gave discouraging results [324]. On the other hand, in a recent 12.7‐year longitudinal study, no direct link was found between normotensive glaucoma and increase risk of devel‐

Whether or not glaucomatous optic neuropathy can be considered an ocular extension during

This work was supported by the Ophthalmological Network OFTARED (RD12‐0034/0002: Prevención, Detección Precoz y Tratamiento de la Patología Ocular Prevalente Degenerativa y Crónica) of the Institute of Health of Carlos III of the Spanish Ministry of Economy. This work has been funded by the PN I+D+i 2008–2011, by the ISCIII‐Subdirección General de Redes y Centros de Investigación Cooperativa and by the European programme FEDER; grants to Elena Salobrar‐Garcia are currently supported by a Predoctoral Fellowship (FPU) from the Spanish Ministry of Education, Culture and Sport. David Nesbitt corrected the English version

, Rosa de Hoz2

1 Ramon Castroviejo Institute of Ophthalmologic Research, School of Medicine, Complutense

2 Ramon Castroviejo Institute of Ophthalmologic Research, School of Optics and Optomet‐

3 Service of Ophthalmology Hospital Gregorio Marañon, Ramon Castroviejo Institute of

4 Service of Geriatrics, University Hospital Clinico San Carlos, Complutense University of

Ophthalmologic Research, Complutense University of Madrid (UCM), Spain

, Alberto Triviño1

, Pilar Rojas3

, Juan J. Salazar2

and José M. Ramírez1\*

,

oping dementia or AD, compared with the general population [325].

Alzheimer's progression deserves further investigation.

, Ana I. Ramírez2

\*Address all correspondence to: ramirezs@med.ucm.es

ry, Complutense University of Madrid (UCM), Spain

, Pedro Gil4

, Raquel Yubero4

University of Madrid (UCM), Spain

**Acknowledgements**

of this work.

402 Update on Dementia

**Author details**

Blanca Rojas1

Elena Salobrar‐García<sup>1</sup>

Madrid (UCM), Spain


[29] Justino L, Kergoat M, Bergman H, Chertkow H, Robillard A, Kergoat H. Neuroretinal function is normal in early dementia of the Alzheimer type. Neurobiology of Aging. 2001; 22: 691–695.

[15] Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL. Retinal abnormalities in early Alzheimer's disease. Investigative Ophthalmology & Visual Science. 2007; 48:

[16] Valenti DA. Neuroimaging of retinal nerve fiber layer in AD using optical coherence

[17] Kesler A, Vakhapova V, Korczyn AD, Naftaliev E, Neudorfer M. Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Clinical Neurology

[18] Moreno‐Ramos T, Benito‐León J, Villarejo A, Bermejo‐Pareja F. Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies,

[19] Garcia‐Martin ES, Rojas B, Ramirez AI, de Hoz R, Salazar JJ, Yubero R, et al. Macular thickness as a potential biomarker of mild Alzheimer's disease. Ophthalmology. 2014;

[20] Salobrar‐Garcia E, Hoyas I, Leal M, de Hoz R, Rojas B, Ramirez AI, et al. Analysis of retinal peripapillary segmentation in early Alzheimer's disease patients. BioMed

[21] Blanks JC, Hinton DR, Sadun AA, Miller CA. Retinal ganglion cell degeneration in

[22] Sadun A, Bassi C. Optic nerve damage in Alzheimer's disease. Ophthalmology. 1990;

[23] Blanks JC, Torigoe Y, Hinton DR, Blanks RHI. Retinal pathology in Alzheimer's disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiology of Aging. 1996; 17: 377–

[24] Blanks JC, Schmidt SY, Torigoe Y, Porrello KV, Hinton DR, Blanks RH. Retinal pathology in Alzheimer's disease. II. Regional neuron loss and glial changes in GCL.

[25] Katz B, Rimmer S, Iragui V, Katzman R. Abnormal pattern electroretinogram in Alzheimer's disease: evidence for retinal ganglion cell degeneration? Annals of

[26] Trick GL, Barris MC, Bickler-Bluth M. Abnormal pattern electroretinograms in patients with senile dementia of the Alzheimer type. Annals of Neurology. 1989; 26: 226–231.

[27] Curcio CA, Drucker DN. Retinal ganglion cells in Alzheimer's disease and aging.

[28] Davies D, McCoubrie P, McDonald B, Jobst K. Myelinated axon number in the optic nerve is unaffected by Alzheimer's disease. British Journal of Ophthalmology. 1995; 79:

and Alzheimer's disease. Journal of Alzheimer's Disease. 2013; 34: 659–664.

2285–2289.

404 Update on Dementia

121: 1149–1151.

97: 9–17.

596–600.

384.

tomography. Neurology. 2007; 69: 1060.

and Neurosurgery. 2011; 113: 523–526.

Research International. 2015; 2015: 636548.

Neurobiology of Aging. 1996; 17: 385–395.

Annals of Neurology. 1993; 33: 248–257.

Neurology. 1989; 26: 221–225.

Alzheimer's disease. Brain Research. 1989; 501: 364–372.


[56] Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diag‐ nostic guidelines for Alzheimer's disease. Alzheimer's and Dementia. 2011; 7: 270–279.

[42] Parisi V, Restuccia R, Fattapposta F, Mina C, Bucci MG, Pierelli F. Morphological and functional retinal impairment in Alzheimer's disease patients. Clinical Neurophysiol‐

[43] Cronin‐Golomb A, Rizzo J, Corkin S, Growdon J. Visual function in Alzheimer's disease and normal aging. Annals of the New York Academy of Sciences. 1991; 640: 28–35.

[44] Lakshminarayanan V, Lagrave J, Kean ML, Dick M, Shankle R. Vision in dementia:

[45] Neargarder SA, Stone ER, Cronin‐Golomb A, Oross S. The impact of acuity on per‐ formance of four clinical measures of contrast sensitivity in Alzheimer's disease. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences. 2003; 58:

[46] Valenti DA. Alzheimer's disease: visual system review. Optometry. 2010; 81: 12–21.

[47] Tzekov RT, Mullan M. Vision function abnormalities in Alzheimer's disease. Survey of

[48] Schlotterer G, Moscovitch M, Crapper‐McLachlan D. Visual processing deficits as assessed by spatial frequency contrast sensitivity and backward masking in normal ageing and Alzheimer's disease. Brain: A Journal of Neurology. 1984; 107: 309–325.

[49] Wright CE, Drasdo N, Harding GF. Pathology of the optic nerve and visual association areas information given by the flash and pattern visual evoked potential, and the

[50] Cronin‐Golomb A, Corkin S, Growdon JH. Contrast sensitivity in Alzheimer's disease. Journal of the Optical Society of America A, Optics, Image Science, and Vision. 1987;

[51] Morris JC. Mild cognitive impairment and preclinical Alzheimer's disease. Geriatrics.

[52] Inzelberg R, Ramirez JA, Nisipeanu P, Ophir A. Retinal nerve fiber layer thinning in

[53] Altintas Ö, Iseri P, Özkan B, Çağlar Y. Correlation between retinal morphological and functional findings and clinical severity in Parkinson's disease. Documenta Ophthal‐

[54] Burkholder BM, Osborne B, Loguidice MJ, Bisker E, Frohman TC, Conger A, et al. Macular volume determined by optical coherence tomography as a measure of neuronal loss in multiple sclerosis. Archives of Neurology. 2009; 66: 1366–1372.

[55] Aaker GD, Myung JS, Ehrlich JR, Mohammed M, Henchcliffe C, Kiss S. Detection of retinal changes in Parkinson's disease with spectral‐domain optical coherence tomog‐

Parkinson disease. Vision Research. 2004; 44: 2793–2797.

raphy. Clinical Ophthalmology. 2010; 4: 1427–1432.

temporal and spatial contrast sensitivity function. Brain. 1987; 110: 107–120.

contrast effects. Neurological Research. 1996; 18: 9–15.

ogy. 2001; 112: 1860–1867.

Ophthalmology. 2013; 59: 414–433.

P54–P62.

406 Update on Dementia

4: 7.

2005; Suppl: 9–14.

mologica. 2008; 116: 137–146.


[85] Sebag J. Ageing of the vitreous. Eye. 1987; 1: 254–262.

[70] Zhu W, Hong J, Zheng T, Le Q, Xu J, Sun X. Age‐related changes of human conjunctiva on in vivo confocal microscopy. British Journal of Ophthalmology. 2010; 94: 1448–1453.

[71] Rada JA, Achen VR, Penugonda S, Schmidt RW, Mount BA. Proteoglycan composition in the human sclera during growth and aging. Investigative Ophthalmology & Visual

[72] Grossniklaus HE, Nickerson JM, Edelhauser HF, Bergman LA, Berglin L. Anatomic alterations in aging and age‐related diseases of the eye. Investigative Ophthalmology

[73] Faragher R, Mulholland B, Tuft S, Sandeman S, Khaw P. Aging and the cornea. British

[74] Gipson IK. Age‐related changes and diseases of the ocular surface and cornea. Inves‐

[75] McMenamin PG, Lee WR, Aitken DA. Age‐related changes in the human outflow

[76] Salvi S, Akhtar S, Currie Z. Ageing changes in the eye. Postgraduate Medical Journal.

[77] Birren JE, Casperson RC, Botwinick J. Age changes in pupil size. Journal of Gerontol‐

[78] Barteselli G, Chhablani J, El‐Emam S, Wang H, Chuang J, Kozak I, et al. Choroidal volume variations with age, axial length, and sex in healthy subjects: a three‐dimen‐

[79] Ramrattan RS, van der Schaft, Theo L, Mooy CM, De Bruijn W, Mulder P, De Jong P. Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in

[80] Pauleikhoff D, Harper CA, Marshall J, Bird AC. Aging changes in Bruch's membrane: a histochemical and morphologic study. Ophthalmology. 1990; 97: 171–178.

[81] Newsome DA, Huh W, Green WR. Bruch's membrane age‐related changes vary by

[82] Ramírez JM, Ramírez AI, Salazar JJ, de Hoz R, Triviño A. Changes of astrocytes in retinal ageing and age‐related macular degeneration. Experimental Eye Research. 2001;

[83] Grunwald JE, Piltz J, Patel N, Bose S, Riva CE. Effect of aging on retinal macular microcirculation: a blue field simulation study. Investigative Ophthalmology & Visual

[84] Moya FJ, Brigatti L, Caprioli J. Effect of aging on optic nerve appearance: a longitudinal

aging. Investigative Ophthalmology & Visual Science. 1994; 35: 2857–2864.

tigative Ophthalmology & Visual Science. 2013; 54: ORSF48–ORSF53.

Science. 2000; 41: 1639–1648.

408 Update on Dementia

2006; 82: 581–587.

73: 601–615.

Science. 1993; 34: 3609–3613.

ogy. 1950; 5: 216–221.

& Visual Science. 2013; 54: ORSF23–ORSF27.

Journal of Ophthalmology. 1997; 81: 814–817.

apparatus. Ophthalmology. 1986; 93: 194–209.

sional analysis. Ophthalmology. 2012;119: 2572–2578.

region. Current Eye Research. 1987; 6: 1211–1221.

study. British Journal of Ophthalmology. 1999; 83: 567–572.


[116] Faden AI, Salzman S. Pharmacological strategies in CNS trauma. Trends in Pharma‐ cological Sciences. 1992; 13: 29–35.

[101] Reed BR, Eberling JL, Mungas D, Weiner M, Kramer JH, Jagust WJ. Effects of white matter lesions and lacunes on cortical function. Archives of Neurology. 2004; 61: 1545–

[102] O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, et al. Vascular

[103] Fratiglioni L, Mangialasche F, Qiu C. Brain aging: lessons from community studies.

[104] Grammas P, Martinez J, Miller B. Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert Reviews in Molecular Medicine.

[105] Mrak RE, Griffin S, Graham DI. Aging‐associated changes in human brain. Journal of

[106] Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, et al. Protective role of reactive astrocytes in brain ischemia. Journal of Cerebral Blood Flow & Metab‐

[107] Frith CD, Frith U. Implicit and explicit processes in social cognition. Neuron. 2008; 60:

[108] Sander M, Bergersen LH, Storm‐Mathisen J. Molecular approaches to understanding neural network plasticity and memory: the Kavli Prize Inaugural Symposium on

[109] Dámaso S, Viadero C. Normal and Pathological changes in aging brain. Revista

[110] Bliss TVP, Lømo T. Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. Journal of

[111] Alvarez VA, Sabatini BL. Anatomical and physiological plasticity of dendritic spines.

[112] VanGuilder HD, Farley JA, Yan H, Van Kirk CA, Mitschelen M, Sonntag WE, et al. Hippocampal dysregulation of synaptic plasticity‐associated proteins with age‐related

[113] Schliebs R, Arendt T. The cholinergic system in aging and neuronal degeneration.

[114] London A, Benhar I, Schwartz M. The retina as a window to the brain‐from eye research

Neuropsicología, Neuropsiquiatría y Neurociencias. 2012; 12: 21–36.

Neuropathology and Experimental Neurology. 1997; 56: 1269–1275.

cognitive impairment. Lancet Neurology. 2003; 2: 89–98.

Nutrition Reviews. 2010; 68: S119–S127.

Neuroscience. Neuroscience. 2009; 163: 965–976.

Annual Review of Neuroscience. 2007; 30: 79–97.

Behavioural Brain Research. 2011; 221: 555–563.

cognitive decline. Neurobiology of Disease. 2011; 43: 201–212.

to CNS disorders. Nature Reviews Neurology. 2013; 9: 44–53.

[115] Ramachandran VS. Encyclopedia of the Human Brain. Academic Press; 2002.

1550.

410 Update on Dementia

2011; 13: e19.

503–510.

olism. 2007; 28: 468–481.

Physiology. 1973; 232: 331–356.


vitro and axonal regeneration in the adult optic nerve in vivo. Journal of Neurochem‐ istry. 2007; 103: 181–189.


[143] Cheung N, Mosley T, Islam A, Kawasaki R, Sharrett AR, Klein R, et al. Retinal micro‐ vascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study. Brain. 2010; 133: 1987–1993.

vitro and axonal regeneration in the adult optic nerve in vivo. Journal of Neurochem‐

[128] Benowitz L, Yin Y. Rewiring the injured CNS: lessons from the optic nerve. Experi‐

[129] David S, Aguayo AJ. Axonal elongation into peripheral nervous system "bridges" after

[130] Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment

[131] Kaur C, Foulds W, Ling E. Blood–retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Progress in Retinal and Eye Research.

[132] Wilbanks GA, Wayne Streilein J. Fluids from immune privileged sites endow macro‐ phages with the capacity to induce antigen-specific immune deviation via a mechanism involving transforming growth factor-β. European Journal of Immunology. 1992; 22:

[133] Taylor A, Streilein J. Inhibition of antigen‐stimulated effector T cells by human

[134] Nassi JJ, Callaway EM. Parallel processing strategies of the primate visual system.

[135] Mandal PK, Joshi J, Saharan S. Visuospatial perception: an emerging biomarker for

[136] Livingstone MS, Hubel DH. Psychophysical evidence for separate channels for the perception of form, color, movement, and depth. Journal of Neuroscience. 1987; 7: 3416–

[137] Maunsell JH, Newsome WT. Visual processing in monkey extrastriate cortex. Annual

[138] Chatterjee S, Callaway EM. Parallel colour‐opponent pathways to primary visual

[139] Roe AW, Ts'o DY. Visual topography in primate V2: multiple representation across

[140] Braddick OJ, O'Brien JM, Wattam‐Bell J, Atkinson J, Hartley T, Turner R. Brain areas

[141] Possin KL. Visual spatial cognition in neurodegenerative disease. Neurocase. 2010; 16:

[142] Zeki S. The disunity of consciousness. Progress in Brain Research. 2007; 168: 11–268.

functional stripes. The Journal of Neuroscience. 1995; 15: 3689–3715.

sensitive to coherent visual motion. Perception‐London. 2001; 30: 61–72.

Alzheimer's disease. Journal of Alzheimer's Disease. 2012; 31: 117–135.

cerebrospinal fluid. Neuroimmunomodulation. 1996; 3: 112–118.

Nature Reviews Neuroscience. 2009; 10: 360–372.

Review of Neuroscience. 1987; 10: 363–401.

cortex. Nature. 2003; 426: 668–671.

central nervous system injury in adult rats. Science. 1981; 214: 931–933.

of nature. Nature Reviews Immunology. 2003; 3: 879–889.

istry. 2007; 103: 181–189.

412 Update on Dementia

2008; 27: 622–647.

1031–1036.

3468.

466–487.

mental Neurology. 2008; 209: 389–398.


[168] Onofrj M, Ghilardi M, Basciani M, Gambi D. Visual evoked potentials in parkinsonism and dopamine blockade reveal a stimulus‐dependent dopamine function in humans. Journal of Neurology, Neurosurgery & Psychiatry. 1986; 49: 1150–1159.

[156] Gundogan FC, Tas A, Erdem U, Sobaci G. Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology. Brain: A Journal of Neurology.

[157] Ghezzi A, Martinelli V, Torri V, Zaffaroni M, Rodegher M, Comi G, et al. Long‐term follow‐up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests. Journal of Neurology. 1999; 246:

[158] Regan D, Silver R, Murray TJ. Visual acuity and contrast sensitivity in multiple sclerosis – hidden visual loss: an auxiliary diagnostic test. Brain: A Journal of Neurology. 1977;

[159] Balcer L, Baier M, Cohen J, Kooijmans M, Sandrock A, Nano‐Schiavi M, et al. Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite.

[160] Fischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, et al. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia.

[161] Monteiro ML, Fernandes DB, Apóstolos‐Pereira SL, Callegaro D. Quantification of retinal neural loss in patients with neuromyelitis optical and multiple sclerosis with or without optic neuritis using Fourier‐domain optical coherence tomography. Investi‐

[162] Frohman E, Costello F, Zivadinov R, Stuve O, Conger A, Winslow H, et al. Optical coherence tomography in multiple sclerosis. Lancet Neurology. 2006; 5: 853–863. [163] Zaveri MS, Conger A, Salter A, Frohman TC, Galetta SL, Markowitz CE, et al. Retinal imaging by laser polarimetry and optical coherence tomography evidence of axonal

degeneration in multiple sclerosis. Archives of Neurology. 2008; 65: 924–928.

[164] Adam CR, Shrier E, Ding Y, Glazman S, Bodis‐Wollner I. Correlation of inner retinal thickness evaluated by spectral‐domain optical coherence tomography and contrast sensitivity in Parkinson disease. Journal of Neuro‐ophthalmology. 2013; 33: 137–142.

[165] Masson G, Mestre D, Blin O. Dopaminergic modulation of visual sensitivity in man.

[166] Moschos MM, Tagaris G, Markopoulos I, Margetis I, Tsapakis S, Kanakis M, et al. Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. European Journal of Ophthalmology. 2011; 21: 24–29. [167] Yu J, Feng Y, Xiang Y, Huang J, Savini G, Parisi V, et al. Retinal nerve fiber layer thickness changes in Parkinson disease: a meta‐analysis. PLoS One. 2014; 9: e85718.

gative Ophthalmology & Visual Science. 2012; 53: 3959–3966.

Fundamental & Clinical pharmacology. 1993; 7: 449–463.

2011; 134: 1–2 /e171.

770–775.

414 Update on Dementia

100: 563–579.

Neurology. 2003; 61: 1367–1373.

Neurology. 2007; 68: 288–291.


[196] Ning A, Cui J, To E, Ashe KH, Matsubara J. Amyloid‐β deposits lead to retinal degen‐ eration in a mouse model of Alzheimer disease. Investigative Ophthalmology & Visual Science. 2008; 49: 5136–5143.

[183] Sivak JM. The aging eye: common degenerative mechanisms between the Alzheimer's brain and retinal disease. Investigative Ophthalmology & Visual Science. 2013; 54: 871–

[184] Ong Y, Ong Y, Ikram MK, Chen CLH, Wong TY, Cheung CY. Potential applications of Spectral‐Domain Optical Coherence Tomography (SD‐OCT) in the study of Alzheim‐

[185] Dehabadi MH, Davis BM, Wong TK, Cordeiro MF. Retinal manifestations of Alzheim‐

[186] Thomson KL, Yeo JM, Waddell B, Cameron JR, Pal S. A systematic review and meta‐ analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.

[187] Kopishinskaya S, Svetozarskiy S. Retinal optical coherence tomography in neuro‐ degenerative diseases (review). Sovremennye Tehnologii v Medicine. 2015; 7: 116–

[188] Parnell M, Guo L, Abdi M, Cordeiro MF. Ocular manifestations of Alzheimer's disease in animal models. International Journal of Alzheimer's Disease. 2012; 2012:

[189] Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, et al. Cytosolic β‐amyloid deposition and supranuclear cataracts in lenses from people with Alzheim‐

[190] Bei L, Shui Y, Bai F, Nelson SK, Van Stavern GP, Beebe DC. A test of lens opacity as an indicator of preclinical Alzheimer Disease. Experimental Eye Research. 2015; 140: 117–

[191] Tsai Y, Lu B, Ljubimov AV, Girman S, Ross‐Cisneros FN, Sadun AA, et al. Ocular changes in TgF344‐AD rat model of Alzheimer's disease. Investigative Ophthalmology

[192] Frost S, Kanagasingam Y, Sohrabi H, Vignarajan J, Bourgeat P, Salvado O, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease.

[193] de la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke.

[194] Bell RD, Zlokovic BV. Neurovascular mechanisms and blood–brain barrier disorder in

[195] Mroczkowska S, Benavente‐Perez A, Patel S, Qin L, Bentham P, Gherghel D. Retinal vascular dysfunction relates to cognitive impairment in Alzheimer disease. Alzheimer

Alzheimer's disease. Acta Neuropathologica. 2009; 118: 103–113.

Disease and Associated Disorders. 2014; 28: 366–367.

er's Disease. Proceedings of Singapore Healthcare. 2014; 23: 74–83.

er's disease. Neurodegenerative Disease Management. 2014; 4: 241–252.

880.

416 Update on Dementia

2015; 1: 136–143.

er's disease. Lancet. 2003; 361: 1258–1265.

& Visual Science. 2014; 55: 523–534.

Translational Psychiatry. 2013; 3: e233.

2002; 33: 1152–1162.

123.

786494.

123.


flammation in transgenic mice expressing human vasculotropic mutant amyloid β precursor protein. American Journal of Pathology. 2005; 167: 505–515.


[220] Katz B, Rimmer S. Ophthalmologic manifestations of Alzheimer's disease. Survey of Ophthalmology. 1989; 34: 31–43.

flammation in transgenic mice expressing human vasculotropic mutant amyloid β

[208] Syed AB, Armstrong RA, Smith C. A quantitative analysis of optic nerve axons in elderly control subjects and patients with Alzheimer's disease. Folia Neuropatholica.

[209] Kusbeci T, Kusbeci OY, Mas NG, Karabekir HS, Yavas G, Yucel A. Stereological evaluation of the optic nerve volume in Alzheimer disease. Journal of Craniofacial

[210] Cuzzo LM, Ross‐Cisneros FN, Yee KM, Wang MY, Sadun AA. Low density lipoprotein receptor‐related protein (LRP) is decreased in optic neuropathy of Alzheimer's disease.

[211] Wang MY, Ross‐Cisneros FN, Aggarwal D, Liang C, Sadun AA. Receptor for advanced glycation end products is upregulated in optic neuropathy of Alzheimer's disease. Acta

[212] Tsai CS, Ritch R, Schwartz B, Lee SS, Miller NR, Chi T, et al. Optic nerve head and nerve fiber layer in Alzheimer's disease. Archives of Ophthalmology. 1991; 109: 199–204.

[213] Kromer R, Serbecic N, Hausner L, Aboul‐enein F, Froelich L, Beutelspacher S. Detection of retinal nerve fiber layer defects in Alzheimer's disease using SD‐OCT. Frontiers in

[214] Danesh‐Meyer H, Birch H, Ku JYF, Carroll S, Gamble G. Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology. 2006; 67:

[215] Scholtz C, Swettenham K, Brown A, Mann D. A histoquantitative study of the striate cortex and lateral geniculate body in normal, blind and demented subjects. Neuropa‐

[216] Dugger BN, Tu M, Murray ME, Dickson DW. Disease specificity and pathologic progression of tau pathology in brainstem nuclei of Alzheimer's disease and progres‐

[217] Iseki E, Matsushita M, Kosaka K, Kondo H, Ishii T, Amano N. Distribution and morphology of brain stem plaques in Alzheimer's disease. Acta Neuropathologica.

[218] Leuba G, Saini K. Pathology of subcortical visual centres in relation to cortical degen‐ eration in Alzheimer's disease. Neuropathology and Applied Neurobiology. 1995; 21:

[219] Parvizi J, Van Hoesen GW, Damasio A. The selective vulnerability of brainstem nuclei

sive supranuclear palsy. Neuroscience Letters. 2011; 491: 122–126.

to Alzheimer's disease. Annals of Neurology. 2001; 49: 53–66.

precursor protein. American Journal of Pathology. 2005; 167: 505–515.

2005; 43: 1–6.

418 Update on Dementia

Surgery. 2015; 26: 1683–1686.

Psychiatry. 2014; 5: 22.

1852–1854.

1989; 78: 131–136.

410–422.

Neuropathologica. 2009; 118: 381–389.

Journal of Neuro‐ophthalmology. 2011; 31: 139–146.

thology and Applied Neurobiology. 1981; 7: 103–114.


[248] Murgatroyd C, Prettyman R. An investigation of visual hallucinosis and visual sensory status in dementia. International Journal of Geriatric Psychiatry. 2001; 16: 709–713.

[234] Buee L, Hof P, Bouras C, Delacourte A, Perl D, Morrison J, et al. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing

[235] Wong‐Riley M, Antuono P, Ho K, Egan R, Hevner R, Liebl W, et al. Cyto‐ chrome oxidase in Alzheimer's disease: biochemical, histochemical, and immuno‐ histochemical analyses of the visual and other systems. Vision Research. 1997;

[236] Leuba G, Saini K. Pathology of subcortical visual centres in relation to cortical degen‐ eration in Alzheimer's disease. Neuropathology and Applied Neurobiology. 1995; 21:

[237] Leuba G, Kraftsik R. Visual cortex in Alzheimer's disease: Occurrence of neuronal death and glial proliferation, and correlation with pathological hallmarks. Neurobiology of

[238] Cronin‐Golomb A, Corkin S, Growdon JH. Visual dysfunction predicts cognitive deficits in Alzheimer's disease. Optometry & Vision Science. 1995; 72: 168–176. [239] Levine DN, Lee JM, Fisher C. The visual variant of Alzheimer's disease A clinicopa‐

[240] Cohen J, Cronin‐Golomb A, Growdon JH, Corkin S. Color vision deficits in Alzheimer's

[241] Martinelli V, Locatelli T, Comi G, Lia C, Alberoni M, Bressi S, et al. Pattern visual evoked potential mapping in Alzheimer's disease correlations with visuospatial impairment.

[242] Baloyannis S. Dendritic pathology in Alzheimer's disease. Journal of the Neurological

[243] Mavroudis IA, Fotiou DF, Manani MG, Njaou SN, Frangou D, Costa VG, et al. Dendritic pathology and spinal loss in the visual cortex in Alzheimer's disease: a Golgi study in

[244] Cronin‐Golomb A, Corkin S, Rizzo JF, Cohen J, Growdon JH, Banks KS. Visual dysfunction in Alzheimer's disease: relation to normal aging. Annals of Neurology.

[245] Mendez MF, Tomsak RL, Remler B. Disorders of the visual system in Alzheimer's

[246] Rizzo M, Nawrot M. Perception of movement and shape in Alzheimer's disease. Brain.

[247] Sadun A, Borchert M, DeVita E, Hinton D, Bassi C. Assessment of visual impairment in patients with Alzheimer's disease. American Journal of Ophthalmology. 1987; 104:

pathology. International Journal of Neuroscience. 2011; 121: 347–354.

disorders. Acta Neuropathologica. 1994; 87: 469–480.

thologic case study. Neurology. 1993; 43: 305.

disease. Society for Neuroscience Abstracts. 1988; 14: 219.

Dementia and Geriatric Cognitive disorders. 1996; 7: 63–68.

disease. Journal of Neuro‐Ophthalmology. 1990; 10: 62–69.

37: 3593–3608.

Aging. 1994; 15: 29–43.

Sciences. 2009; 283: 153–157.

1991; 29: 41–52.

1998; 121: 2259–2270.

113–120.

410–422.

420 Update on Dementia


[277] Trick GL, Silverman SE. Visual sensitivity to motion age-related changes and deficits in senile dementia of the Alzheimer type. Neurology. 1991; 41: 1437–1437.

[262] Cronin‐Golomb A, Gilmore GC, Neargarder S, Morrison SR, Laudate TM. Enhanced stimulus strength improves visual cognition in aging and Alzheimer's disease. Cortex.

[263] Rami L, Serradell M, Bosch B, Villar A, Molinuevo JL. Perception Digital Test (PDT) for the assessment of incipient visual disorder in initial Alzheimer's disease. Neurologia.

[264] Curran S, Wilson S, Musa S, Wattis J. Critical Flicker Fusion Threshold in patients with Alzheimer's disease and vascular dementia. International Journal of Geriatric Psychia‐

[266] Carmel D, Lavie N, Rees G. Conscious awareness of flicker in humans involves frontal

[267] Mendola JD, Cronin‐Golomb A, Corkin S, Growdon JH. Prevalence of visual deficits in Alzheimer's disease. Optometry and Vision Science. 1995; 72: 155–167.

[268] Curran S, Wattis J. Critical flicker fusion threshold: a potentially useful measure for the early detection of Alzheimer's disease. Human Psychopharmacology: Clinical and

[269] Jackson GR, Owsley C, McGwin G. Aging and dark adaptation. Vision Research. 1999;

[271] Kiyosawa M, Bosley T, Chawluk J, Jamieson D, Schatz N, Savino P, et al. Alzheimer's disease with prominent visual symptoms. Clinical and metabolic evaluation. Ophthal‐

[272] Mendez M, Chekrier M, Meadows R. Depth perception in Alzheimer's disease.

[273] Thiyagesh SN, Farrow TF, Parks RW, Accosta‐Mesa H, Young C, Wilkinson ID, et al. The neural basis of visuospatial perception in Alzheimer's disease and healthy elderly comparison subjects: an fMRI study. Psychiatry Research: Neuroimaging. 2009; 172:

[274] Vaney DI, Sivyer B, Taylor WR. Direction selectivity in the retina: symmetry and asymmetry in structure and function. Nature Reviews Neuroscience. 2012; 13: 194–208.

[275] Chapman C, Hoag R, Giaschi D. The effect of disrupting the human magnocellular pathway on global motion perception. Vision Research. 2004; 44: 2551–2557.

[276] Skottun B. On the use of visual motion perception to assess magnocellular integrity.

[270] Blake R, Wilson H. Binocular vision. Vision Research. 2011; 51: 754–770.

mology. 1989; 96: 1077–1085; discussion 1085–1086.

Journal of Integrative Neuroscience. 2011; 10: 15–32.

Perceptual and Motor Skills. 1996; 83: 987–995.

[265] Valdés M, De Flores T. Psychobiology of stress. Barcelona: Martínez Roca; 1985.

and parietal cortex. Current Biology. 2006; 16: 907–911.

2007; 43: 952–966.

422 Update on Dementia

2007; 22: 342–347.

try. 2004; 19: 575–581.

Experimental. 2000; 15: 103–112.

39: 3975–3982.

109–116.


[303] Strenn K, Dal‐Bianco P, Weghaupt H, Koch G, Vass C, Gottlob I. Pattern electroretino‐ gram and luminance electroretinogram in Alzheimer's disease. Journal of Neural Transmission Suppl. 1991; 33: 73–80

[291] Treloar A, Assin M, MacDonald A. Pupillary response to topical tropicamide as a marker for Alzheimer's disease. British Journal of Clinical Pharmacology. 1996; 41: 256–

[292] Gómez-Tortosa E, Barrio A, Jiménez-Alfaro I. Pupil response to tropicamide in Alzheimer's disease and other neurodegenerative disorders. Acta Neurologica

[293] Granholm E, Morris S, Galasko D, Shults C, Rogers E, Vukov B. Tropicamide effects on pupil size and pupillary light reflexes in Alzheimer's and Parkinson's disease. Inter‐

[294] Grünberger J, Linzmayer L, Walter H, Rainer M, Masching A, Pezawas L, et al. Receptor test (pupillary dilatation after application of 0.01% tropicamide solu‐ tion) and determination of central nervous activation (Fourier analysis of pupil‐ lary oscillations) in patients with Alzheimer's disease. Neuropsychobiology. 1999;

[295] Hou R, Samuels E, Raisi M, Langley R, Szabadi E, Bradshaw C. Why patients with Alzheimer's disease may show increased sensitivity to tropicamide eye drops: role of

[296] Iijima A, Haida M, Ishikawa N, Ueno A, Minamitani H, Shinohara Y. Re‐evaluation of tropicamide in the pupillary response test for Alzheimer's disease. Neurobiology of

[297] Kaneyuki H, Mitsuno S, Nishida T, Yamada M. Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease. Neurology. 1998; 50: 802–804.

[298] Reitner A, Baumgartner I, Thuile C, Dilmaghani R, Ergun E, Kaminsky S, et al. The mydriatic effect of tropicamide and its diagnostic use in Alzheimer's disease. Vision

[299] Levin LA, Nilsson SFE, Ver Hoeve J, Wu S, Kaufman PL, Alm A. Adler's physiology

[300] Rüb U, Del Tredici K, Schultz C, Büttner‐Ennever J, Braak H. The premotor region essential for rapid vertical eye movements shows early involvement in Alzheimer's disease‐related cytoskeletal pathology. Vision research. 2001; 41: 2149–

[301] Boxer AL, Garbutt S, Seeley WW, Jafari A, Heuer HW, Mirsky J, et al. Saccade abnor‐ malities in autopsy‐confirmed frontotemporal lobar degeneration and Alzheimer

[302] McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, et al. ISCEV Standard for full‐field clinical electroretinography (2015 update). Documenta

national Journal of Psychophysiology. 2003; 47: 95–115.

locus coeruleus. Psychopharmacology. 2006; 184: 95–106.

of the eye. Elsevier Health Sciences; 2011. p. 796.

disease. Archives of Neurology. 2012; 69: 509.

Ophthalmologica. 2015; 130: 1–12.

257.

424 Update on Dementia

40: 40–46.

2156.

Aging. 2003; 24: 789–796.

Research. 1997; 37: 165–168.

Scandinavica. 1996; 94: 104–109.

