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Flash and Pattern Reversal Visual Evoked Responses in Normal and Demented Elderly
NOTE FLASH AND PATTERN REVERSAL VISUAL EVOKED RESPONSES IN NORMAL AND DEMENTED ELDERLY Eric E. Brodie\ Donald Allan1 , David N. Brooks3 , James McCulloch3 and Wallace S. Foulds4 ewellcome Neuroscience Group, University of Glasgow, now at the Department of Psychology, Glasgow Polytechnic, Glasgow; 2West of Scotland Health Board, Department of Clinical Physics and Bio-Engineering, Glasgow, now at the Paterson Institute for Cancer Research, Manchester; 3Wellcome Neuroscience Group, University of Glasgow; 4-fennent Institute of Ophthalmology, Western Infirmary, Glasgow, now at the Nuffield Hospital, Glasgow)
INTRODUCTION
Alzheimer's Disease (AD) is a progressive neuro-degenerative disorder which is tradi tionally thought to spare sensory receptors, pathways and areas of cortex. However neu roanatomical evidence suggests that there is degeneration of the neuronal populations in volved with a variety of sensory receptor sites and pathways. For example, degeneration has been found in both the retina and optic nerve of patients with AD (Hinton, Sadum, Blanks et al., 1989) and in receptors of the olfactory epithelium (Talamo, Rudel, Kosik et al., 1989). Visual processing deficits in the demented elderly have received scant attention even though many complain of not being able to see properly. The majority of the research has concentrated on those deficits presenting earliest such as memory loss (for review see Morris and Kopelman, 1986). A few studies have investigated visual capabilities of patients with AD, though with equivocal results. For example, some studies have found no change in contrast sensitivity function for AD patients (Schlotterer, Moscovitch and Crapper-McLachlan, 1983; Wright, Drasdo and Harding, 1987) and some have found a consistent loss in sensitivity ac ross the spatial frequency range (Nissen, Corkin, Buonanno et al., 1985; Sadun, Borchert, DeVita et al., 1987). However most research is carried out on patients in the early stages of the disease. This is in part due to difficulty in testing moderate and/or severe patients who may have problems in comprehending and following instructions, have limited attention spans and have difficulty in expressing themselves. The use of the visual evoked response (VER) overcomes many of the problems associated with testing moderate/severe AD pa tients as they are only required to fixate on a screen. The aim of this study was to test moderate AD patients in order to find out whether the degeneration of neuronal populations is reflected in poor primary visual performance. This may manifest itself by an increase in the latency of the VER components to flash stimuli. Additionally the use of pattern reversal stimuli at high and low spatial frequencies and high and low contrast may reveal deficits of secondary visual performance. Previous comparisons of AD patients and normal elderly have used high contrast stimuli only. MATERIALS AND METHOD
Subjects Seven patients (all female) were recruited from a longitudinal study investigating AD. All patients were living at home, though with varying amounts of help, and no patient had a sev ere physical or visual disability. In order to overcome some of the problems associated with the diagnosis of AD, the Cambridge Mental Disorders of the elderly Examination (CAMDEX) (Roth, Tym, Mo untjoy et al., 1986) was used. The CAMDEX criteria include a gradual intellectual deteriorCortex, (1992) 28, 289-293
E. E. Brodie and Others
290
ation for at least 6 months with the exclusion of possible reversible dementias, other psy chiatric disorders, other neurological diseases, diabetes and malignancy and cases of sever ley impaired vision and audition. All patients also received Electrocardiogram, Electroen cephalogram, and single photon emission computed tomography (SPECT) scans. Patients were selected for the AD group only when no other possible cause of dementia could be con sidered. All patients were rated as moderately demented according to CAMDEX criteria. Seven elderly controls (6 female 1 male) were recruited from an old peoples club and a hospital geriatric day unit. The controls were screened medically before entering the group. Informed consent was obtained for all patients and controls.
Apparatus and Procedure Stimulus presentation and signal recording were controlled by an Apple lie microcom puter. VER's were recorded simultaneously from two channels using active electrodes over the left and right occiputs at 0 1 and 0 2 and a common reference at Fz. An electrode at Cz was ground. Responses were passed through an amplifier of 50000 gain and bandpass from 2 Hz to 100Hz (- 3 dB points) and averaged over 128 repetitions by the microcomputer. Flash stimulation by diffuse illumination of a circular 40° field at a viewing distance of 25 em was provided by the flash unit of a Medelec OS5 stimulator system. For pattern rev ersal the subjects viewed from 2 m distance a regular check pattern generated by the Medelec OS5 on a monochrome television monitor. The screen subtense was 8° by 10° and check siz es of 86 and 22 minutes of arc were displayed at either high, virtually 1000Jo, contrast or at approximately 25% contrast. With either stimulus type, the stimulus repetition frequency was 1.3 Hz. Subjects wore usual spectacle correction appropriate to the viewing distance. Snellen visual acuities were also noted, tested monocularly and with any appropriate spectacle correction. RESULTS
Table I shows patient and control details. The mean age of the AD patients is slightly higher than that of the controls though visual acuity is comparable. Cognitive status was measured using the CAMCOG: a component of the CAMDEX. The CAMCOG is a short mental status examination similar to the Mini-mental State examination [MMSE] (Folstein, Folstein and McHugh, 1975) though is more extensive than the MMSE in the areas of cog nition included. However the MMSE is included in the CAMCOG and MMSE scores can be generated. These are presented in order to facilitate the comparison of mental status of sub jects with other studies. Figure 1 shows the mean P1 and P2 components of the flash stimuli for AD patients and TABLE I
Details of Patients and Controls Visual acuity Subjects
N
AD
7
Controls
7
Age
Left eye
Right eye
MMSE
CAMCOG Mean (S.D.) 42 (14) 63 (26)
Mean (S.D.)
Median (range)
Median (range)
Mean (S.D.)
79.2 (3.4) 76.9 (4.8)
6/9 (6/9-6/60) 6/9 (6/6-6/60)
6/12 (6/9-6/60) 6/12 (6/9-6/24)
11 (4) 19 (8)
MMSE: Mini-mental State Examination (Folstein et al., 1975). CAMCOG: Cognitive section of the CAMDEX (Roth et al., 1986).
Visual evoked responses and dementia
• •
200
-ui
-
Controls AD patients
29I
Fig. l - Visual evoked res ponses to flash stimulation for AD and normal elderly: Mean and standard deviation of Pl and P2 components.
150
E
> c
100
as
50
u
Cl)
..J
P1
P2
Component
controls. It can be seen that the latencies for both PI and P2 are longer for the AD patients than for the controls. Analysis of covariance was performed upon the data with age as the covariant. The difference between the AD patients and the controls for the PI component was found not to be significant (F = 2.66; d.f. =I, 11; p >0.05) and the difference for the P2 component was found to be significant (F = 6.89; d.f. = I, 11; p < 0.05). Figure 2 shows the mean PIOO component for the high and low contrast and high and low spatial frequency pattern reversal stimuli. It can be seen that PIOO latencies for pattern reversal are longer for the AD patients than for the controls. Analysis of covariance, with age as the covariant, revealed a significant difference between the AD patients and the con trols for the small pattern reversal stimuli at low contrast (F= I4.72; d.f. =I, 11; p0.5). There was no significant difference found for large pattern at either high (F= 1.04; d.f. =I, 11; p>0.05) or low contrast (F= 1.09; d.f. =I, 11; p>0.05).
ui
••
200
150
Controls AD patients
E
> ucCl) as
-
100
50
..J
Large/high
Large/low
Small/high
Small/low
Size/Contrast of Pattern
Fig. 2 - Visual evoked res ponses to pattern reversal for AD and normal elderly: Mean and standard deviation of PJOO com ponents at high and low contrast and at high and low spatial fre quency.
292
E.E. Brodie and Others DISCUSSION
In this study moderate AD patients differed from controls on the P1 and P2 component of flash stimulation with the latter achieving statistical significance. These results supple ment the finding of Harding, Wright and Orwin (1985), who tested patients with mild AD and found a slowing of both P 1 and P2 components of the VER to flash stimulation with the P2 component being found to be significantly slower. A study with larger numbers of sub jects is required to confirm the slowing of.the P1 component, especially for moderate AD patients. These results are in keeping with the neuropathologic evidence of neuronal dege neration of the retina and visual pathways (Hinton et al., 1989). The results for pattern reversal stimulation would suggest that there is a loss of sensitiv ity at high spatial frequencies and low contrast for AD patients as on the pattern reversal at high spatial frequency at low contrast a significant difference was found. Harding et al. (1985), using early and established cases of AD, found no difference for the YEP to pattern reversal. However they did not explore the extremes of spatial frequency or contrast. There sults of this study would suggest that primary visual cortex is not functioning normally in the moderately demented AD patient. The extent of neuronal degeneration in the visual cortex in AD has not yet been explored systematically. However in the occipital cortex of AD patients there are abundant senile pla ques and neurofibrillary tangles and reduced levels of cholineacetyltransferase, the biosyn thetic enzyme for acetylcholine (Rogers and Morrison, 1985; Lewis, Campbell, Terry et al., 1987; Araujo, Lapchak, Robitaille et al., 1988; Hof, Bouras, Constantinidis et al., 1989; Esiri, Pearson, Steele et al., 1990). The fact that there is a loss of sensitivity at high spatial frequencies and low contrast in moderate AD patients was confirmed by the first author when administering the National Adult Reading Test (NART, 1" Edition) (Nelson and O'Connor, 1978). The AD patients performed very poorly when presented with the standard card. When the size and contrast of the words were increased, performance improved. These results would suggest that as Alzheimer's Disease follows its course, the visual processing capabilities of AD patients decrease. The design and administration of cognitive test batteries must take account of these findings. ABSTRACT
P1 and P2 components· of visual evoked responses (VERs) to flash stimuli were com pared between patients diagnosed as suffering from Senile Dementia of the Alzheimer Type (AD) and elderly controls. Additionally the P100 component of the VER to pattern reversal stimuli at high and low contrast and using large and small check patterns was compared. Sig nificant differences between moderate AD patients and the normal elderly were found for the P2 component of the flash stimulus and for the P100 component of the high spatial fre quency pattern reversal stimuli at low contrast. These findings suggest a deficit in primary visual processing and a selective deficit in secondary visual processing in moderate cases of dementia. This indicates that visual processing capacities of AD patients decline as the di sease progresses in line with the continual degeneration of neuronal populations involved with vision.
Acknowledgements. This study was funded by the Wellcome Trust Grant 18738/1.19. F. McGregor, S. Wylie and D. Montaldi are thanked for medical, nursing and psychological help respectively. REFERENCES
ARAUJO, D.M., LAPCHAK, P.A., ROBITAILLE, Y., GAUTHIER, S., and QUIRION, R. Differential alteration of various cholinergic markers in cortical and subcortical regions of human.brain in Alzheimer's Di sease. Journal ofNeurochemistry, 50: 1914-1923, 1988. ESIRI, M.M., PEARSON, R.C.A., STEELE, J.E., BOWEN, D.M., and POWELL, T.P.S. A quantitative study
Visual evoked responses and dementia
293
of the neurofibrillary tangles and the choline acetyltransferase activity in the cerebral cortex and the amygdala in Alzheimer's Disease. Journal ofNeurology, Neurosurgery and Psychiatry, 53: 161-165, 1990. FOLSTEIN, M.F., FOLSTEIN, S.E., and McHUGH, P.R. "Mini-mental State". A practical method for grad ing the cognitive state of patients for the clinician. Journal ofPsychiatric Research, 12: 189-198, 1975. HARDING, G.F.A., WRIGHT, C.E., and ORWIN, A. Primary presenile dementia: The use of the visual evoked potential as a diagnostic indicator. British Journal of Psychiatry, 147: 532-539, 1985. HINTON, D.R., SADUM, A.A., BLANKS, J.C., and MILLER, C.A. Optic-nerve degeneration in Alzheimer's Disease. The New England Journal ofMedicine, 315: 485-487, 1989. HOF, P.R., BouRAS, C., CONSTANTINIDIS, J., and MORRISON, J.H. Balint's syndrome in Alzheimer's Di sease: specific disruption of the occipito-parietal visual pathway. Brain Research, 493: 368-375, 1989. LEWIS, D.A., CAMPBELL, M.J., TERRY, R.D., and MORRISON, J.H. Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's Disease: A quantitative study of visual and auditory cortices. The Journal ofNeuroscience, 7: 1799-1808, 1987. MoRRIS, R.G., and KoPELMAN, M.D. The memory deficits in Alzheimer-type dementia: A review. The Quarterly Journal ofExperimental Psychology, 38: 575-602, 1986. NELSON, H.E., and O'CoNNOR, A. Dementia: The estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex, 14: 234-244, 1978. NISSEN, M.J., CORKIN, S., BUONANNO, F.S., GROWDON, J.H., WRAY, S.H., and BAUER, J. Spatial vision in Alzheimer's disease. Archives ofNeurology, 42: 667-671, 1985. RoGERS, J., and MoRRISON, J.H. Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's Disease. The Journal ofNeuroscience, 5: 2801-2808, 1985. ROTH, M., TYM, E., MOUNTJOY, C.Q., HUPPERT, F.A., HENDRIE, H., VERMA, S., and GODDARD, R. CAMDEX. A standardised instrument for the diagnosis of mental disorders of the elderly with spe cial reference to the early detection of dementia. British Journal ofPsychiatry, 149: 698-709, 1986. SADUN, A.A., BORCHERT, M., DEVITA, E., HINTON, D.R., and BASSI, C.J. Assessment of visual impair ment in patients with Alzheimer's disease. American Journal ofOphthalmology, 104: 113-120, 1987. SCHLOTTERER, G., MoSCOVITCH, M., and CRAPPER-MCLACHLAN, D. Visual processing deficits as as sessed by spatial frequency contrast sensitivity and backward masking in normal ageing and Alzhei mer's disease. Brain, 107: 309-325, 1983. TALAMO, B.R., RUDEL, R.A., KOSIK, K.S., LEE, V.M.-Y., NEFF, S.L., and KAUER, J.S. Pathological changes in olfactory neurons in patients with Alzheimer's disease. Nature, 377: 736-739, 1989. WRIGHT, C.E., DRASDO, N., and HARDING, G.F.A. Pathology of the optic nerve and visual association areas. Brain, 110: 107-120, 1987. Dr. E.E. Brodie, Dept. Psychology, Glasgow Politechnic, cowcaddens Road Glasgow, 64 OBA, Scotland, UK.
INTRODUCTION
Alzheimer's Disease (AD) is a progressive neuro-degenerative disorder which is tradi tionally thought to spare sensory receptors, pathways and areas of cortex. However neu roanatomical evidence suggests that there is degeneration of the neuronal populations in volved with a variety of sensory receptor sites and pathways. For example, degeneration has been found in both the retina and optic nerve of patients with AD (Hinton, Sadum, Blanks et al., 1989) and in receptors of the olfactory epithelium (Talamo, Rudel, Kosik et al., 1989). Visual processing deficits in the demented elderly have received scant attention even though many complain of not being able to see properly. The majority of the research has concentrated on those deficits presenting earliest such as memory loss (for review see Morris and Kopelman, 1986). A few studies have investigated visual capabilities of patients with AD, though with equivocal results. For example, some studies have found no change in contrast sensitivity function for AD patients (Schlotterer, Moscovitch and Crapper-McLachlan, 1983; Wright, Drasdo and Harding, 1987) and some have found a consistent loss in sensitivity ac ross the spatial frequency range (Nissen, Corkin, Buonanno et al., 1985; Sadun, Borchert, DeVita et al., 1987). However most research is carried out on patients in the early stages of the disease. This is in part due to difficulty in testing moderate and/or severe patients who may have problems in comprehending and following instructions, have limited attention spans and have difficulty in expressing themselves. The use of the visual evoked response (VER) overcomes many of the problems associated with testing moderate/severe AD pa tients as they are only required to fixate on a screen. The aim of this study was to test moderate AD patients in order to find out whether the degeneration of neuronal populations is reflected in poor primary visual performance. This may manifest itself by an increase in the latency of the VER components to flash stimuli. Additionally the use of pattern reversal stimuli at high and low spatial frequencies and high and low contrast may reveal deficits of secondary visual performance. Previous comparisons of AD patients and normal elderly have used high contrast stimuli only. MATERIALS AND METHOD
Subjects Seven patients (all female) were recruited from a longitudinal study investigating AD. All patients were living at home, though with varying amounts of help, and no patient had a sev ere physical or visual disability. In order to overcome some of the problems associated with the diagnosis of AD, the Cambridge Mental Disorders of the elderly Examination (CAMDEX) (Roth, Tym, Mo untjoy et al., 1986) was used. The CAMDEX criteria include a gradual intellectual deteriorCortex, (1992) 28, 289-293
E. E. Brodie and Others
290
ation for at least 6 months with the exclusion of possible reversible dementias, other psy chiatric disorders, other neurological diseases, diabetes and malignancy and cases of sever ley impaired vision and audition. All patients also received Electrocardiogram, Electroen cephalogram, and single photon emission computed tomography (SPECT) scans. Patients were selected for the AD group only when no other possible cause of dementia could be con sidered. All patients were rated as moderately demented according to CAMDEX criteria. Seven elderly controls (6 female 1 male) were recruited from an old peoples club and a hospital geriatric day unit. The controls were screened medically before entering the group. Informed consent was obtained for all patients and controls.
Apparatus and Procedure Stimulus presentation and signal recording were controlled by an Apple lie microcom puter. VER's were recorded simultaneously from two channels using active electrodes over the left and right occiputs at 0 1 and 0 2 and a common reference at Fz. An electrode at Cz was ground. Responses were passed through an amplifier of 50000 gain and bandpass from 2 Hz to 100Hz (- 3 dB points) and averaged over 128 repetitions by the microcomputer. Flash stimulation by diffuse illumination of a circular 40° field at a viewing distance of 25 em was provided by the flash unit of a Medelec OS5 stimulator system. For pattern rev ersal the subjects viewed from 2 m distance a regular check pattern generated by the Medelec OS5 on a monochrome television monitor. The screen subtense was 8° by 10° and check siz es of 86 and 22 minutes of arc were displayed at either high, virtually 1000Jo, contrast or at approximately 25% contrast. With either stimulus type, the stimulus repetition frequency was 1.3 Hz. Subjects wore usual spectacle correction appropriate to the viewing distance. Snellen visual acuities were also noted, tested monocularly and with any appropriate spectacle correction. RESULTS
Table I shows patient and control details. The mean age of the AD patients is slightly higher than that of the controls though visual acuity is comparable. Cognitive status was measured using the CAMCOG: a component of the CAMDEX. The CAMCOG is a short mental status examination similar to the Mini-mental State examination [MMSE] (Folstein, Folstein and McHugh, 1975) though is more extensive than the MMSE in the areas of cog nition included. However the MMSE is included in the CAMCOG and MMSE scores can be generated. These are presented in order to facilitate the comparison of mental status of sub jects with other studies. Figure 1 shows the mean P1 and P2 components of the flash stimuli for AD patients and TABLE I
Details of Patients and Controls Visual acuity Subjects
N
AD
7
Controls
7
Age
Left eye
Right eye
MMSE
CAMCOG Mean (S.D.) 42 (14) 63 (26)
Mean (S.D.)
Median (range)
Median (range)
Mean (S.D.)
79.2 (3.4) 76.9 (4.8)
6/9 (6/9-6/60) 6/9 (6/6-6/60)
6/12 (6/9-6/60) 6/12 (6/9-6/24)
11 (4) 19 (8)
MMSE: Mini-mental State Examination (Folstein et al., 1975). CAMCOG: Cognitive section of the CAMDEX (Roth et al., 1986).
Visual evoked responses and dementia
• •
200
-ui
-
Controls AD patients
29I
Fig. l - Visual evoked res ponses to flash stimulation for AD and normal elderly: Mean and standard deviation of Pl and P2 components.
150
E
> c
100
as
50
u
Cl)
..J
P1
P2
Component
controls. It can be seen that the latencies for both PI and P2 are longer for the AD patients than for the controls. Analysis of covariance was performed upon the data with age as the covariant. The difference between the AD patients and the controls for the PI component was found not to be significant (F = 2.66; d.f. =I, 11; p >0.05) and the difference for the P2 component was found to be significant (F = 6.89; d.f. = I, 11; p < 0.05). Figure 2 shows the mean PIOO component for the high and low contrast and high and low spatial frequency pattern reversal stimuli. It can be seen that PIOO latencies for pattern reversal are longer for the AD patients than for the controls. Analysis of covariance, with age as the covariant, revealed a significant difference between the AD patients and the con trols for the small pattern reversal stimuli at low contrast (F= I4.72; d.f. =I, 11; p
ui
••
200
150
Controls AD patients
E
> ucCl) as
-
100
50
..J
Large/high
Large/low
Small/high
Small/low
Size/Contrast of Pattern
Fig. 2 - Visual evoked res ponses to pattern reversal for AD and normal elderly: Mean and standard deviation of PJOO com ponents at high and low contrast and at high and low spatial fre quency.
292
E.E. Brodie and Others DISCUSSION
In this study moderate AD patients differed from controls on the P1 and P2 component of flash stimulation with the latter achieving statistical significance. These results supple ment the finding of Harding, Wright and Orwin (1985), who tested patients with mild AD and found a slowing of both P 1 and P2 components of the VER to flash stimulation with the P2 component being found to be significantly slower. A study with larger numbers of sub jects is required to confirm the slowing of.the P1 component, especially for moderate AD patients. These results are in keeping with the neuropathologic evidence of neuronal dege neration of the retina and visual pathways (Hinton et al., 1989). The results for pattern reversal stimulation would suggest that there is a loss of sensitiv ity at high spatial frequencies and low contrast for AD patients as on the pattern reversal at high spatial frequency at low contrast a significant difference was found. Harding et al. (1985), using early and established cases of AD, found no difference for the YEP to pattern reversal. However they did not explore the extremes of spatial frequency or contrast. There sults of this study would suggest that primary visual cortex is not functioning normally in the moderately demented AD patient. The extent of neuronal degeneration in the visual cortex in AD has not yet been explored systematically. However in the occipital cortex of AD patients there are abundant senile pla ques and neurofibrillary tangles and reduced levels of cholineacetyltransferase, the biosyn thetic enzyme for acetylcholine (Rogers and Morrison, 1985; Lewis, Campbell, Terry et al., 1987; Araujo, Lapchak, Robitaille et al., 1988; Hof, Bouras, Constantinidis et al., 1989; Esiri, Pearson, Steele et al., 1990). The fact that there is a loss of sensitivity at high spatial frequencies and low contrast in moderate AD patients was confirmed by the first author when administering the National Adult Reading Test (NART, 1" Edition) (Nelson and O'Connor, 1978). The AD patients performed very poorly when presented with the standard card. When the size and contrast of the words were increased, performance improved. These results would suggest that as Alzheimer's Disease follows its course, the visual processing capabilities of AD patients decrease. The design and administration of cognitive test batteries must take account of these findings. ABSTRACT
P1 and P2 components· of visual evoked responses (VERs) to flash stimuli were com pared between patients diagnosed as suffering from Senile Dementia of the Alzheimer Type (AD) and elderly controls. Additionally the P100 component of the VER to pattern reversal stimuli at high and low contrast and using large and small check patterns was compared. Sig nificant differences between moderate AD patients and the normal elderly were found for the P2 component of the flash stimulus and for the P100 component of the high spatial fre quency pattern reversal stimuli at low contrast. These findings suggest a deficit in primary visual processing and a selective deficit in secondary visual processing in moderate cases of dementia. This indicates that visual processing capacities of AD patients decline as the di sease progresses in line with the continual degeneration of neuronal populations involved with vision.
Acknowledgements. This study was funded by the Wellcome Trust Grant 18738/1.19. F. McGregor, S. Wylie and D. Montaldi are thanked for medical, nursing and psychological help respectively. REFERENCES
ARAUJO, D.M., LAPCHAK, P.A., ROBITAILLE, Y., GAUTHIER, S., and QUIRION, R. Differential alteration of various cholinergic markers in cortical and subcortical regions of human.brain in Alzheimer's Di sease. Journal ofNeurochemistry, 50: 1914-1923, 1988. ESIRI, M.M., PEARSON, R.C.A., STEELE, J.E., BOWEN, D.M., and POWELL, T.P.S. A quantitative study
Visual evoked responses and dementia
293
of the neurofibrillary tangles and the choline acetyltransferase activity in the cerebral cortex and the amygdala in Alzheimer's Disease. Journal ofNeurology, Neurosurgery and Psychiatry, 53: 161-165, 1990. FOLSTEIN, M.F., FOLSTEIN, S.E., and McHUGH, P.R. "Mini-mental State". A practical method for grad ing the cognitive state of patients for the clinician. Journal ofPsychiatric Research, 12: 189-198, 1975. HARDING, G.F.A., WRIGHT, C.E., and ORWIN, A. Primary presenile dementia: The use of the visual evoked potential as a diagnostic indicator. British Journal of Psychiatry, 147: 532-539, 1985. HINTON, D.R., SADUM, A.A., BLANKS, J.C., and MILLER, C.A. Optic-nerve degeneration in Alzheimer's Disease. The New England Journal ofMedicine, 315: 485-487, 1989. HOF, P.R., BouRAS, C., CONSTANTINIDIS, J., and MORRISON, J.H. Balint's syndrome in Alzheimer's Di sease: specific disruption of the occipito-parietal visual pathway. Brain Research, 493: 368-375, 1989. LEWIS, D.A., CAMPBELL, M.J., TERRY, R.D., and MORRISON, J.H. Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's Disease: A quantitative study of visual and auditory cortices. The Journal ofNeuroscience, 7: 1799-1808, 1987. MoRRIS, R.G., and KoPELMAN, M.D. The memory deficits in Alzheimer-type dementia: A review. The Quarterly Journal ofExperimental Psychology, 38: 575-602, 1986. NELSON, H.E., and O'CoNNOR, A. Dementia: The estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex, 14: 234-244, 1978. NISSEN, M.J., CORKIN, S., BUONANNO, F.S., GROWDON, J.H., WRAY, S.H., and BAUER, J. Spatial vision in Alzheimer's disease. Archives ofNeurology, 42: 667-671, 1985. RoGERS, J., and MoRRISON, J.H. Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's Disease. The Journal ofNeuroscience, 5: 2801-2808, 1985. ROTH, M., TYM, E., MOUNTJOY, C.Q., HUPPERT, F.A., HENDRIE, H., VERMA, S., and GODDARD, R. CAMDEX. A standardised instrument for the diagnosis of mental disorders of the elderly with spe cial reference to the early detection of dementia. British Journal ofPsychiatry, 149: 698-709, 1986. SADUN, A.A., BORCHERT, M., DEVITA, E., HINTON, D.R., and BASSI, C.J. Assessment of visual impair ment in patients with Alzheimer's disease. American Journal ofOphthalmology, 104: 113-120, 1987. SCHLOTTERER, G., MoSCOVITCH, M., and CRAPPER-MCLACHLAN, D. Visual processing deficits as as sessed by spatial frequency contrast sensitivity and backward masking in normal ageing and Alzhei mer's disease. Brain, 107: 309-325, 1983. TALAMO, B.R., RUDEL, R.A., KOSIK, K.S., LEE, V.M.-Y., NEFF, S.L., and KAUER, J.S. Pathological changes in olfactory neurons in patients with Alzheimer's disease. Nature, 377: 736-739, 1989. WRIGHT, C.E., DRASDO, N., and HARDING, G.F.A. Pathology of the optic nerve and visual association areas. Brain, 110: 107-120, 1987. Dr. E.E. Brodie, Dept. Psychology, Glasgow Politechnic, cowcaddens Road Glasgow, 64 OBA, Scotland, UK.