Visual Impairment in Alzheimer'sDisease

by Nichole Cook


The documentation of a severe form of dementia by Alois Alzheimerin 1907 began a massive investigation of the cause of this disorder.Some of the common symptoms of Alzheimer's Disease consist of memoryloss, impaired language ability, impaired judgement, and learning (M.Wong, et al. , 1997). Alzheimer's Disease (AD) is mainly a disease ofthe cerebral cortex. Alzheimer's is marked structurally by the senileplaques, neurofibrillary tangles, and severe loss of neurons andsynapses in the cerebral cortex. Alzheimer's is a neurodegenerativedisorder ( Hof, Vogt, Bouras, and Morrison 1997). Recent attentionhas been focused on visual dysfunction in Alzheimer's Disease (K. U.Loffler, D. P. Edward, & M. O. M. Tso 1995).

Visual Problems

During the clinical evaluation of patients with mild to moderatedementia of the AD type, visual difficulties such as : topographicagnosia, visual agnosia, alexia without agraphia, and prosopagnosiaare detected. AD patients have The problem of describing theindividual components of a picture is consistent with the severity ofcytochrome oxidase (C.O.) deficits in the association cortical areas.Other deficits experienced by AD patients were texturediscrimination, blue-violet discrimination, and 4.72 deg/sec motiondetection. When AD patients were compared to other age-matchedcontrols, AD patients had shown specific deficits in contrastsensitivity. Deficits in color vision were only age-related (M.Wong-Riley, et al. , 1997).



Selective degeneration of large ganglion cell axons was observedin the optic nerves of AD patients, which suggested an impairment ofbroad-band channel visual function. Although studies show that thebroad-band visual capabilities are not selectively impaired in AD.Dorsal LGN studies have shown that both the magno- and parvicellularneurons were greatly affected in AD patients. Strangely, AD patientswere impaired at low frequencies instead of the high frequencies,like in old age. This implies that regions controlling the lowspacial frequency processing in the primary visual cortex would beaffected more than those for high frequency processing (M.Wong-Riley, et al. , 1997). The neuropathologic examination of thebrains with visual impairment in the Hof et al. (1997) study revealedcortical atrophy dominating on the posterior parietal cortex andoccipital lobe(Hof et al.). A study by Beta-amyloid is considered animportant factor in AD and was shown to be the major cause in senileplaques.


A number of neurotransmitters and neuromodulators, includingacetylcholine (ACh), somatostatin and glutamate have been found to bedeficient in Alzheimer's disease (AD). A degree of ACh activity isnecessary in visual information processing, higher functions, memory,learning and other cognitive processes (L. Nobili, & W. G.Sannita 1997). Recent studies have focused on possible defects inenergy metabolism in AD. The major source of energy supply forneurons is ATP, which is generated mainly from oxidative metabolismin the mitochondria (Wong-Riley, et. al. , 1997).

A major decline in cholinergic markers is the main feature inAlzheimer's Disease. Cholinergic agonists and antagonists have beenused as test conditions in investigating the role of ACh in visualinformation processing. The brain ACh systems depend on experienceand sensory input in early development. If there is any visualdeprivation during this critical time, ACh cannot properly performits function. ACh also increases the firing rate for ON- andOFF-center ganglion cells, requiring differential sensitivity. In thevisual cortex and the hippocampus, ACh is a long lasting excitatoryagent, which monitors the level of temporal patterns of neuralactivity. Somatosensory cortex studies indicate that ACh enhancesresponsiveness by lowering the threshold to stimulation, and possiblyincreasing the receptive field size ( L. Nobili & W. G. Sannita1997).

Cytochrome Oxidase

A reliable and sensitive indicator of a neuron's capacity foroxidative metabolism is cytochrome oxidase (C.O.). The level of thisenzyme is extremely regulated by neuronal activity. Activity of C.O.has shown to be greatly decreased in AD patients. The activity ofC.O. has been studied in different brain regions of AD cases. Theexact location that C.O. was defective in activity is unknown.Studies in the primary visual cortex show that there is not asignificant reduction in its regional metabolism rate when a PET scanis performed, even though many AD patients have reported visualdifficulties. M. Wong-Riley et al. (1997) performed a study toevaluate the presence of senile plaques and the levels of C.O. invarious parts of the brain in AD patients and non-AD patients. Theresults show that there were more neuritic plaques within theparietal cortex of the AD group. The neuritic plaques met theKhachaturian criterion level for AD in the primary and secondaryvisual cortical areas as well as many other cortical areas. It isclear that all of the cortical regions had shown a significantdecrease in C.O. activity. The greatest reduction of C.O. activitywas displayed in the majority of the cortex layers. In AD, thehistochemically and immunohistochemically analyzed levels of C.O.were systematically lower in the supra-, infra-, and granular layersof the cortical areas. Cytochrome oxidase levels are significantlyreduced in the visual system of AD. Both the dorsal lateralgeniculate nucleus (LGN) and the visual cortex exhibited significantreductions in C.O. levels and protein amount as compared to thecontrol group. The primary visual cortex of the AD patients hadplaque density comparable to the affected prefrontal and insularcortices.


Beta-amyloid is derived from the amyloid precursor protein (APP).K. U. Loffler, D. P. Edward, and M. O. M. Tso (1995) conducted astudy to compare degeneration in the retina with the degeneration ofan AD brain slice. They found that there is no relation between thetau protein in the retina and retinal aging. Beta-amyloid and APP canbe related with retinal aging and retinal degeneration (K. U.Loffler, D. P. Edward, & M. O. Tso 1995).


he difficulty in finding a cure for Alzheimer's Disease is thatmost, if not all, of the abnormalities are interrelated. A defect inone area would lead to another area. Some studies have concluded thatif a person continuously learns and exercises the brain, there is aless likely chance the person will experience Alzheimer's diseasesymptoms (W. J. Streit & C. A. Kincade-Colton 1995).



Loffler, K. U. , Edward, D. P. , & Tso, M. O. M. (1995) .Immunoreactivity against tau, amyloid precursor protein, andbeta-amyloid in the human retina. Investigative Ophthalmology& Visual Science, 36, 24-31.

Hof, P. R. , Vogt, B. A. , Bouras, C. , & Morisson, J. H.(1997). Atypical form of Alzheimer's disease with prominent posteriorcortical atrophy: a review of lesion distribution and circuitdisconnection in cortical visual pathways. Vision Research,37, 3609-3622.

Kuljis, R. , & Tikoo, R. (1997). Discontinuous distribution ofsenile plaques within striate cortex hyper columns in Alzheimer'sdisease. Vision Research, 37 (24) , 3573-3589.

Nobili, L. , & Sannita, W. (1997). Cholinergic modulation,visual function and Alzheimer's dementia. Vision Research, 37,(24) , 3559-3567.

Wong-Riley, M. , Antuoni, P. , Ho, K. , Egan, R. , Hevner, R. ,Liebl, W. , Huang, Z. , Rachel, R. , Jones, J. (1997). Cytochromeoxidase in Alzheimer's disease: biochemical, historical, andimmunohistochemical analyses of the visual and other systems.Vision Research, 37, 3593-3607.

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