Visual Impairment in Alzheimer's Disease

by Nichole Cook

Introduction

The documentation of a severe form of dementia by Alois Alzheimer in 1907 began a massive investigation of the cause of this disorder. Some of the common symptoms of Alzheimer's Disease consist of memory loss, impaired language ability, impaired judgement, and learning (M. Wong, et al. , 1997). Alzheimer's Disease (AD) is mainly a disease of the cerebral cortex. Alzheimer's is marked structurally by the senile plaques, neurofibrillary tangles, and severe loss of neurons and synapses in the cerebral cortex. Alzheimer's is a neurodegenerative disorder ( Hof, Vogt, Bouras, and Morrison 1997). Recent attention has 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 moderate dementia of the AD type, visual difficulties such as : topographic agnosia, visual agnosia, alexia without agraphia, and prosopagnosia are detected. AD patients have The problem of describing the individual components of a picture is consistent with the severity of cytochrome oxidase (C.O.) deficits in the association cortical areas. Other deficits experienced by AD patients were texture discrimination, blue-violet discrimination, and 4.72 deg/sec motion detection. When AD patients were compared to other age-matched controls, AD patients had shown specific deficits in contrast sensitivity. Deficits in color vision were only age-related (M. Wong-Riley, et al. , 1997).

Studies

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

Acetylcholine

A number of neurotransmitters and neuromodulators, including acetylcholine (ACh), somatostatin and glutamate have been found to be deficient in Alzheimer's disease (AD). A degree of ACh activity is necessary 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 in energy metabolism in AD. The major source of energy supply for neurons is ATP, which is generated mainly from oxidative metabolism in the mitochondria (Wong-Riley, et. al. , 1997).

A major decline in cholinergic markers is the main feature in Alzheimer's Disease. Cholinergic agonists and antagonists have been used as test conditions in investigating the role of ACh in visual information processing. The brain ACh systems depend on experience and sensory input in early development. If there is any visual deprivation during this critical time, ACh cannot properly perform its function. ACh also increases the firing rate for ON- and OFF-center ganglion cells, requiring differential sensitivity. In the visual cortex and the hippocampus, ACh is a long lasting excitatory agent, which monitors the level of temporal patterns of neural activity. Somatosensory cortex studies indicate that ACh enhances responsiveness by lowering the threshold to stimulation, and possibly increasing the receptive field size ( L. Nobili & W. G. Sannita 1997).

Cytochrome Oxidase

A reliable and sensitive indicator of a neuron's capacity for oxidative metabolism is cytochrome oxidase (C.O.). The level of this enzyme is extremely regulated by neuronal activity. Activity of C.O. has shown to be greatly decreased in AD patients. The activity of C.O. has been studied in different brain regions of AD cases. The exact location that C.O. was defective in activity is unknown. Studies in the primary visual cortex show that there is not a significant reduction in its regional metabolism rate when a PET scan is performed, even though many AD patients have reported visual difficulties. M. Wong-Riley et al. (1997) performed a study to evaluate the presence of senile plaques and the levels of C.O. in various parts of the brain in AD patients and non-AD patients. The results show that there were more neuritic plaques within the parietal cortex of the AD group. The neuritic plaques met the Khachaturian criterion level for AD in the primary and secondary visual cortical areas as well as many other cortical areas. It is clear that all of the cortical regions had shown a significant decrease in C.O. activity. The greatest reduction of C.O. activity was displayed in the majority of the cortex layers. In AD, the histochemically and immunohistochemically analyzed levels of C.O. were systematically lower in the supra-, infra-, and granular layers of the cortical areas. Cytochrome oxidase levels are significantly reduced in the visual system of AD. Both the dorsal lateral geniculate nucleus (LGN) and the visual cortex exhibited significant reductions in C.O. levels and protein amount as compared to the control group. The primary visual cortex of the AD patients had plaque density comparable to the affected prefrontal and insular cortices.

Beta-Amyloid

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

Conclusion

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

References

Loffler, K. U. , Edward, D. P. , & Tso, M. O. M. (1995) . Immunoreactivity against tau, amyloid precursor protein, and beta-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 posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways. Vision Research, 37, 3609-3622.

Kuljis, R. , & Tikoo, R. (1997). Discontinuous distribution of senile plaques within striate cortex hyper columns in Alzheimer's disease. 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). Cytochrome oxidase in Alzheimer's disease: biochemical, historical, and immunohistochemical analyses of the visual and other systems. Vision Research, 37, 3593-3607.