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Disorders of the Visual System in Alzheimer's Disease

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Disorders of the Visual System in Alzheimer's Disease © 1990 Raven Press, Ltd.. New York Disorders of the Visual System in Alzheimer's Disease Mario F. Mendez, M.D., Robert L. Tomsak, M.D., Ph.D., and Bernd Remler, M.D. Alzheimer's disease (AD) is associated with distur­ Alzheimer's disease (AD) is the most prevalent bances in basic visual, complex visual, and oculomotor form of dementia affecting greater than 2.5 million functions. The broad range of visual system disorders in AD may result from the concentration of neuropathol­ people in the U.S., with the numbers expected to ogy in visual association cortex and optic nerves in this double by the year 2040 (1). Despite the absence of disease. AD patients and their caregivers frequently re­ a clinical test for AD, the recent establishment of port visuospatial difficulties in these patients. Examina­ highly accurate clinical criteria permit a more pre­ tion of the visual system in AD may reveal visual field cise evaluation of the deficits associated with this deficits, prolonged visual evoked potentials, depressed contrast sensitivities, and abnormal eye movement re­ disorder (2-4) (see Table 1). In addition to the cordings. Complex visual disturbances include construc­ usual memory and other cognitive deficits, AD pa­ tional and visuoperceptual abnormalities, spatial agno­ tients have disturbances in basic visual, complex sia and Balint's syndrome, environmental disorienta­ visual, and oculomotor functions, and AD patients tion, visual agnosia, facial identification problems, and in greater numbers are undergoing more thorough visual hallucinations. The purpose of this article is to review the spectrum of visual system disturbances evaluations of their visual systems (4-8). found in AD and, in particular, to describe the methods Physicians are just beginning to understand the used to screen for complex visual abnormalities in these significance of visual system involvement in AD patients. (9,10). Consistent with the clinical heterogeneity of Key Words: Alzheimer's disease-Dementia­ this disorder, individuals with AD vary in the ex­ Visual-Visual perception-Visuospatial-Balint's syn­ drome---Oculomotor. tent of their visual system pathology and in their visual problems (7,11). The visual system prob­ lems are not simply due to global cognitive impair­ ment and can occur in the absence of other cogni­ tive deficits, increased dementia severity, or pro­ longed duration of dementia (4). However, the visual system abnormalities may contribute greatly to the disability caused by AD and may magnify the effects of other cognitive deficits. For these rea­ sons, any management strategies that improve vi­ sual functions can help alleviate the huge burden of taking care of these patients. Furthermore, there is a need to both identify higher visual tests that could be used for the early diagnosis of AD and to determine the visual physiological mechanisms that are disturbed in dementia. From the Alzheimer Center and the Department of Neurol­ ogy (M.F.M.) and the Division of Neuro-Ophthalmology, De­ NEUROPHYSIOLOGY partment of Neurology, and Department of Ophthalmology AND NEUROPATHOLOGY (R. L. T., B.R.), University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio. AD affects the visual association cortex with rel­ Address correspondence and reprint requests to Dr. M. F. ative sparing of primary visual areas (12-14). Se­ H.,· !. f'... I I' Medic,1 C"nter, Jackson University, nile plaques are located throughout the visual cor- 62 VISUAL SYSTEM AND AD 63 TABLE 1. NINCDS-ADRDA criteria for clinically TABLE 2. Visual symptoms in 30 patients with probable Alzheimer's disease (2) Alzheimer's disease (4) '(1) Dementia established by clinical exam and Spatial agnosia: Five patients had prominent difficulties documented by mental status questionnaire or finding objects, looking at them, and reaching for neuropsychological testing them. These patients were unable to walk without (2) Deficits in two or more areas of cognition bumping into things and could not judge distances. (3) Progressive worsening Visual localization problems: Seven additional patients (4) No disturbance of consciousness had less severe difficulties visually finding objects. (5) Onset between the ages of 40 and 90 Environmental disorientation: Five patients had an (6) Absence of other potentially causative disorder(s), isolated problem finding their way in familiar such as systemic disorders or brain disease, that surroundings that was not due to a general spatial could account for dementia agnosia. Spatial alexia: Three patients had reading difficulties not due to language disturbances or a general spatial agnosia. On reading, these patients easily lost their tex; however, in early and middle stages of AD, place, neurofibrillary tangles, which are associated with Possible mild optic ataxia: Two patients had difficulties with fine hand-eye coordination tasks that was not the severity of dementia (15), are located in greater due to general spatial agnosia. amounts in higher visual areas (12,13), Neurofibril­ Visual agnosia: Three patients had difficulty recognizing lary tangles are rare in area 17, increase 20-fold in common objects when visually presented. Facial identification problems: One patient had area 18, and nearly double again in area 20 (13), prosopagnosia. Positron emission tomography scanning studies Visual hallucinations: Three patients had formed also show cerebral hemispheric hypometabolism hallucinations that were not otherwise explainable by medications or confusional states. concentrated in the posterior parietal lobes and ad­ joining areas, with sparing of the primary visual occipital cortex (16-18), This distribution of neuro­ pathological and metabolic changes predicts pre­ without bumping into things), in visual localiza­ dominant deficits in complex visual functions (19), tion (e.g., finding door handles or other common Furthermore, the pattern of complex visual distur­ objects), in environmental orientation (e.g., find­ bances in AD, with prominent visuospatial prob­ ing their way in their surroundings), in reading lems, suggests differential disease of the magno­ (e.g., locating the next word or line of print), and cellular-occipitoparietal visual system, dealing in performing fine hand-eye coordination activi­ with spatial concepts, rather than the parvocellu­ ties (e.g., sewing) (4-9) (see Table 2). AD patients lar-occipitotemporal visual system, dealing with and their caregivers complain less frequently of form and color (20-22), difficulties in visually identifying objects, scenes, In addition to the greater disease in visual asso­ or faces (5) and of visual hallucinations (26). ciation areas, there is prominent optic nerve de­ Examination of the visual system in AD patients generation in AD, with dropout of retinal ganglion reveals a broad range of disturbances. All visual cells and their axons ranging from 15 to 80% (6), functions are not uniformly affected in AD; there One study found decreased retinal M cell degen­ are specific patterns of involvement. Frequently eration in 8 of 10 patients (23). This optic neurop­ impaired basic visual functions include peripheral athy results in minimal clinical evidence of visual vision, visual evoked potentials (VEPs), and con­ impairment (6), and most of the observed visual trast sensitivities (4,6,24,25,27,28). Difficulties with system abnormalities in AD probably result from constructions, figure-ground discrimination, and disease in visual association cortex. However, a visual synthesis are present in the majority of pa­ late decrease in visual acuity and color vision may tients with AD and are the most common findings be consequences of the optic neuropathy in AD potentially attributable to complex visual dysfunc­ (4,6,7,24,25). tion in this disorder (4,29). Other common com­ plex visual abnormalities involve visuospatial abil­ ities (4-9) and visual object and face recognition CLINICAL EVALVAnON (4-9). Finally, patients with AD have abnormal oc­ The most common visual complaints in AD are ulomotor functions, such as increased saccadic la­ problems in visuospatial functioning (4-8). In a tency and an inability to inhibit anticipatory sac­ study of 30 community-based patients with clini­ cades (30-35). The rest of this article discusses spe­ cally probable AD, almost half (43%) had visual cific visual system abnormalities in AD and visual symptoms, and these were predominantly visuo­ system testing in demented patients, particularly spatial (4) (see Table 2). Visuospatial difficulties oc­ the screening tests used for complex visual distur­ cur in general spatial orientation (e.g., walking bances (see Table 3). 1Clin Neuro-{)phthalmol, Vol. 10, No. 1, 1990 64 M. F. MENDEZ ET AL. TABLE 3. Screening test for complex cific verbal answer. Ultimately, clinicians must in­ visual functions terpret critically the results of visual system testing Constructions: Two-dimensional design or cube, in demented patients, as abnormal performance three-dimensional cube or open box, complex design, may be due to a combination of several visual and e.g., clock face cognitive disturbances. Perception: Tests of figure-ground discrimination (overlapping, cross-hatched, or hidden figures) and visual synthesis tasks (completion or visual closure tasks) BASIC VISUAL FUNCTIONS Visuospatial: Tests of inattention or neglect (line bisections), localization (dot circling or picture Investigations of basic visual functions in AD searching), simultanagnosia ("linked" versus have found abnormalities particularly
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