134

Journal of the Neurological Sciences, l 11 (1992) 134-142 © 1992 ElsevierSciencePublishers B.V. All rights reserved 0022-510X/92/$05.00

JNS 03822

Actively and passively evoked P3 latency of event-related potentials in Parkinson's disease H i s a o T a c h i b a n a , K a z u o T o d a a n d M i n o r u gugita Fifth Department of Internal Medicine, Hyogo Collegeof Medicine, Nishinomiya, Japan

(Received 10 September, 1991) (Revised, received 20 February, 1992) (Accepted 2 March, 1992) Key words: P300 (1'3); Event-related potentials (ERP); Parkinson's disease; Alzheimer's disease; Dementia

Summary Event-related potentials (ERPs) generated during the performance of visual discrimination tasks were studied in 31 patients with Parkinson's disease, 9 patients with AIzheimer's disease, and 37 normal control subjects. Actively and passively evoked 1)3 components (P3b and P3a) were respectively identified as the components of the P3 response to infrequent target stimuli and infrequent non-target stimuli. Both the P3a and P3b latencies were significantly prolonged by normal aging. Nine of the Parkinson's disease patients showed a P3b latency above the 95% confidence limit of the age-adjusted regression line based on the normal controls, while only one patient had a prolonged P3a latency. In 6 patients with demented Parkinson's disease, the P3b latency was significantly longer than in 15 age-equivalent normal subjects, although no significant d~fference was found in the P3a latency, On the other hand, patients with Alzheimer's disease showed significant prolongation of both the P3a and P3b latencies compared to the normal controls. Furthermore, there was a significant difference in P3a latency between patients with demented Parkinson's disease and those with Alzheimer's disease. These results suggest that the automatic processing stage associated with P3a may be less impaired than the attention-controlled processing reflected by P3h in patients with Parkinson's disease, and also indicate that there may be some differences in the changes of cognitive processing caused by Parkinson's disease and Alzheimer's disease.

Introduction Intellectual deficit is well recognized as a feature of Parkinson's disease at the present time (Brown and Marsden 1988a), although the precise characteristics of the cognitive dysfunction remains controversial. Despite the many investigations of the neuropathological features (Hakim and Mathieson 1979; Jellinger 1987), transmitter abnormalities (Agid et al. 1986; Dubois et al. 1987), radiographic alterations (Lichter et al. 1988), and neuropsychological changes (Huber et al. 1986; Freedman and Oscar-Bergman 1989; Mohr et al. 1990) associated with parkinsonian dementia, it is still unclear whether or not the differences between Parkinson's and Alzheimer's dementia outweigh their similarities.

Correspondence to: Hisao Tachibana, MD, Fifth Department of Internal Medicine, HyogoCollege of Medicine, l-l, Mukogawa-cho, Nishinomiya 663, Japan. Tel.: (0798) 45-6596; Fax: (0798)45-6597.

Electrophysiological investigations have also focused on cognitive function in patients with Parkinson's disease. P300 (P3) is a long-latency positive component of the scalp-recorded, event-related potential (ERP) that is known to be related to cognitive processing (Donchin et al. 1978; Hansch et al. 1982). Several groups (Hansch et ai. 1982; Goodin and Aminoff 1986, 1987; Higasa et al. 1987; Tachibana et al. 1991) have shown that the latency of the P3 component generated by active target detection tasks is delayed in patients with Parkinson's disease relative to normal controls. Two types of P3 have been reported in normal subjects with relation to the visual (Courchesne et al. 1975; Beck et al. 1980),. auditory (Polich et al. 1985; Knight 1987) and somatosensory (Yamaguchi and Knight 1991a, b) modalities. One is a parietal maximal 1)3 component designated as P3b and the other is a frontocentral (Knight 1987; Yamaguchi and Knight 1991a, b) or sometimes parietal (Beck et al. 1980; Polich et al. 1985) maximal P3 component named P3a. P3b is elicited by task-relevant stimuli under conditions

135 of active attention and its latency of P3b appears to be determined by the stimulus evaluation time (McCarthy and Donchin 1981). P3a is elicited as an N2-P3a complex by unexpected neutral stimuli under conditions of passive attention (Squires et al 1975; Rallo 1986). Since this P3a response is passively evoked by rare stimuli unassociated with task demands, it has also been designated as the passive P3 (O'Donnel et al. 1990) or the novelty P3 (Beck et al 1980) and may represent a central nervous system component of the orienting response (Squires et al. 1975; Snyder and Hillyard 1976). Knight (1984) showed prefrontal cortex to be closely related to the P3a component. Frontal lobe dysfunction has been reported in neuropsychological (Piccirili et ai. 1989; Taylor et al. 1990) and cerebral blood flow studies (Beset al. 1983) on patients with Parkinson's disease. Although the P3b component has already been investigated in many clinical sudies, there have been few studies of the P3a component. The purpose of the present study was to investigate the P3a and P3b components of ERPs in patients suffering from Parkinson's disease with and without dementia by using visual discrimination tasks, and to compare the results obtained in demented Parkinson's disease with those obtained in Alzheimer's disease.

TABLE 1 CLINICAL C H A R A C T E R I S T I C S PARKINSON'S DISEASE No. of subjects Sex M / F Age (years, mean :i: SD) Duration of disease (years, mean + SD) Stage (Hoehn-Yahr scale, 1967) (n) I II II! IV V Antiparkinsonian therapy (n) None Dopa a Anticholinergics b Dopa + anticholinergics Dopa + bromocriptine Dopa + bromocriptine + anticholinergics Dopa + bromocriptine + amantadine Bromocriptine + anticholinergics Dopa + anticholinergics + amantadine + bromocriptine

OF

PATIENTS

WITH

31 5/26 66.9 + 8.4 3.2 + 3.1 2 15 12 2 0 4 9 1 10 1 2 1 1

2

a With dopa-decarboxTlase inhibitors (carbidopa or benzerazide). b Trihexyphenidyl.

Materials and methods The study was performed in 31 patients with Parkinson's disease (mean age 66.9 + 8.4 years, range 50-80 years), 9 patients with Alzheimer's disease (mean age 73.6 + 8.8 years, range 56-86 years), and 37 normal controls (mean age 47.0 + 20.1 years, range 19-91 years) without a history of neurological disease or drug abuse. Patients with Parkinson's disease presented at least two or more of its cardinal features (bradykinesia, tremor, or rigidity), and these had developed insidiously. Patients with any evidence of focal lesions on CT scans and an ischemic score (Hachinski et al. 1975) greater than 4 were excluded. In all cases, the diagnosis of clementia was based on the results of neurological and neuropsychological examinations and was made according to the criteria outlined in DSM-III-R (American Psychiatric Association 1987). The severity of dementia was assessed using Hasegawa's Dementia Scale (HDS) (Hasegawa 1983), and the severity of motor disability was determined by the Hoehn and Yahr Scale (Hoohn and Yahr 1967). The HDS consists of five subtests to measure orientation, general information, calculation, memory recall, and memorization. It includes 11 questions and the full score is 32.5 points. Increasing lower scores reflect greater cognitive impairment. Table 1 shows the clinical characteristics of the 31 Parkinson's disease patients. Six patients (19.4%) met

the DSM-III-R criteria for dementia. Of these 6 demented patients, 3 were receiving L-Dopa plus trihexiphenydil, one was receiving L-Dopa alone and 2 were on no antiparldnsonian drugs. As shown in Table 2, there were no significant differences in antiparkinsonian medication for the demented and nondemented patients. Apart from 4 patients without any antiparkinsonian medication, the other 27 remained on treatment throughout the study period. The study was performed during the "on stage" in all patients. Alzheimer's disease patients met DSM-III-R criteria for primary degenerative dementia, as well as the criteria of the National Institute of Neurological and Communicative Disorders/Stroke-Alzheimer's Disease and Related Disorders Association (NINCDSADRDA) work group for probable dementia of the Alzheimer type (McKhann et al. 1984). All these paTABLE 2 ANTIPARKINSONIAN MEDICATION IN PATIENTS WITH NONDEMENTED AND DEMENTED PARKINSON'S DISEASE

L-Dopa (mg) Trihe~jphenidyl (rag) Bromocriptine(mg) Amantadine (mg)

Demented patients

Non-demented patients

316.7 + 271.4 3.0+ 3.3 2.9+ 3.7 33.3 + 81.6

295.7 + 163.7 3.3 + 3.3 2.1+ 2.7 24.0 + 59.7

136 tients also met research criteria for the diagnosis of senile dementia of the Alzheimer type (Morris e t a i . 1988). Patients with heart disease, vascular disease, or psychiatric disorders were excluded. All had shown a progressive nonstepwise clinical course, and no other cause for their altered mental function was revealed by various investigations. None of these patients showed clinical motor abnormalities with parkinsonian features. In addition, in all Alzheimer's disease patients EEG was normal or demonstrated mild slowing, CT scan demonstrated mild-to-moderate cortical atrophy, and the ischemic score was always 3 or less. The criteria for Alzheimer's diesease proposed by the NINCDS-ADRDA work group have shown a high degree of accuracy in studies that included histopathologic validation, with correct classification rates ranging from 80 to 100% (Morris etai. 1988; Boiler et at. 1989). In our study, the diagnosis of Alzheimer's disease was not confirmed by histopathological examination. Clinical characteristics of the patients are summarized in Table 3. There were no significant differences among the three groups in age, but there were significant differences in the duration of illness and the HDS score. Concerning the duration cf illness, no significant difference was observed for post-hoc pairwise comparison. A significant difference was noted in the HDS score between patients with demented and hondomerited Parkinson's disease, although there was no significant difference between those with demented Parkinson's disease and Alzheimer's disease. There was no significant difference in Hoehn-Yahr stage (X 2 = 4.73; P > 0.1) between the two Parkinson's disease groups. Also no marked differences between patients with nondemented and demented Parkinson's disease were found with regard to clinical signs of parkinsonism.

Frequent Non-TargetStimulus

Rare Target Stimulus

Rare Non-Target,Stimulus

Fig. 1. Three types of stimuliwere used: frequent non-target, rare target, and rare non-target. ERPs were recorded in a sound-attenuated electrically shielded chamber. The EEG was recorded using Ag/AgC! electrodes placed on scalp sites Fz, Cz, and Pz (International 10-20 system), with a reference electrode to the linked earlobes. An electrode to measure eye movements (EOG) was placed below the left inferior orbit. Electrode impedance was maintained below 5 k ~ . The EEG and ocular activity data were amplified (filter 0.02-50 Hz) and stored together with event markers on a harddisc after A - D conversion for off-line analysis. Three kinds of stimuli (Fig. 1) were displayed on a TV screen: a rare target, a rare non-target, and a frequent non-target. These were presented sequentially in a random order with probabilities of 0.19, 0.19, and 0.62, respectively. Stimulus duration was 66 msec. The interstimulus interval (offset to onset) was 1240 msec. Rare target stimuli were designated as targets to be responded to by the subject, while the remaining stimuli were assigned as background to be ignored. A total of 256-320 visual stimuli were generated by the computer and displayed on the TV screen. Although some authors have used an infrequent non-target stimulus with a very low probability ( < 5%) ( N l i t i n e n et at. 1982) and quite different from the other stimuli in the

TABLE3 COMPARISONOF CLINICALCHARACTERISTICSBETWEENPATIENTSWITHNONDEMENTEDOR DEMEN~rEDPARKINSON'S DISEASE AND THOSE WITHALZHEIMER'SDISEASE

No. of subjects Ale (years) Duration of illness (years) Hasegawa'sdementia scale score Yahr's scale

Parkinson'sdisease Demented(A) Nondemented(13) 6 25 70.7 + 11.3 66.0 + 7.6

9 73.6± 8.8

F

1.2 ± 1.1

4.42 *

21.5 + 5.0

30.5 + 2.1

21.3 ± 5.3

6.36 **

I!I IV V

4 1 0

2

14 8 1 0

A/C

B/C

3.27

2.7 + 2.6

0 1

A/B

(Bonferroni'stest)

5.4 ± 4.1

I II

* P < 0.05, ** P < 0.01.

Alzheimer'disease (C)

**

**

137 experiment (eg. a face (Rallo 1986) or a color pattern (Courchesne et al. 1975)) to elicit the P3a component, others (Pfefferbaum et al. 1984) have elicited it using the 3 shape visual stimuli comparable to our study: a plus sign, the frequent stimulus, occurred 72% of the time; a triangle with the apex up and a triangle with the apex down, the infrequent stimuli, each occurred 14% of the time, One of the 2 types of the infrequent stimuli was designated as a target to which subjects were instructed to press the key with the index finger of the hand they used most often. The subjects were comfortably seated in a dimly lit chamber with the TV display positioned approximately one meter in front of their eyes. They were requested to continuously keep their eyes on the center of the TV screen and to minimize head movements, eye movements and blinking. The instructions were to respond to rare targets by pressing a button as quickly and accurately as possible, and to ignore all other stimuli. The experiment was preceded by a training period. Incorrect responses were noted for less than 10% of the rare target stimuli presented. Subjects used their dominant forefinger for pressing the button. To obtain ERP data, EEGs free from ocular or other artifacts were averaged separately for the three kinds of stimuli from 200 msec before stimulus onset to 1200 msec after the onset. The sampling rate for averaging was 10 msec per point. P3 components were evaluated by subtracting the E R P for frequent stimuli from that for rare stimuli (Fig. 2), so as to isolate endogenous components related to probability and task demands (Walsleben et al. 1989). The P3a component was identified as a positive-going potential consisting of a component of the N2-P3a complex at the Cz site

(Squires et ai. 1975; N~iifiinen et al. 1982), which occurred 200-500 msec following the onset of infrequent non-target stimuli. The P3b component was identified as the largest positive-going potential at the Pz site between 300 and 700 msec after the onset of infrequent target stimuli. Latency of the P3 peak was determined from the recordings made at all 3 electrode sites and was defined as time in msec from stimulus onset to the component itself. Peak amplitudes were measured relative to the prestimulus baseline. Results were expressed as the mean :1: SD. Statistical analysis was performed using one-way ANOVA (F-test) or the x2-test to compare different groups. Where significant intergroup differences were detected by ANOVA, Bonferroni's test was used for post-hoe pairwise comparison. Pearson's r-values were calculated to determine correlation coefficients. The criterion for significance was P < 0.05.

Results

P3a latency increased with age in 37 normal subjects (r = 0.62, P < 0.001, P3a latency - 1.00 X age + 264.6) (Fig. 3). A significant positive correlation was noted between P3b latency and age (r = 0.64, P < 0.001, P3b latency = 1.40 X age + 345.1) (Fig. 4). In only one patient with Parkinson's disease, P3a latency was prolonged beyond 2 SE (standard error) of the appropriate age-related value estimated from the regression line (Fig. 3). Nine patients including 5 with dementia had prolonged P3b latency (Fig. 4). Of 6 demented patients, one patient (16.7%) showed prolonged P3a latency and 4 (66.7%) prolonged P3b

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138 P3a Latency (reset)

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Fig. 3. P3a latency data for the patients with Parkinson's disease. The normal regression line is plotted with lines representing 4-2 SE based on the normal control subjects. In only 1 patient with demented Parkinson's disease was the P3a latency prolonged beyond 2 SE from the age-adjusted regression line.

Fig. 4. P3b latency data for the patients with Parkinson's disease. The normal regression line is plotted with lines representing 4-2 SE based on the normal control subjects. Nine patients who included 4 demented with Parkinson's disease had a prolonged P3b latency.

latency. In 25 patients with nondemented Parkinson's disease, prolonged latency was noted in 5 (20%) for P3b and in none for P3a. Prolonged P3b latency was significantly greater in patients with demented Parkinson's disease than in nondemented patients (X 2= 5. 11, e < 0.05). P3a latencies in the patients with Parkinson's disease, those with Alzheimer's disease, and the ageequivalent normal controls are shown in Table 4. Age. equivalent normal controls were 15 subjects more than 50 years old from among the 37 normal controls, and were for comparison of ERP test results. Significant intergroup differences were noted in P3a and P3b latencies. In patients with demented Parkinson's disease, P3b latency was significantly longer than in those

with nondemented Parkinson's disease and in normal controls. No significant differences in P3a latency among the groups could be found. Patients with Alzheimer's disease showed significant prolongation of P3a and P3b latencies compared to the normal controis. Significant difference in P3a latency was evident between patients with demented Parkinson's disease and those with Alzheimer's disease. No significant differences in P3a and P3b amplitudes could be found among the 4 groups. Representative difference ERP waves in patients with demented and nondemented Parkinson's disease, a patient with Aizheimer's disease and a normal subject are shown in Fig. 5. P3a and P3b latency was compared for therapy groups, since antiparkinsonian medication has been

TABLE 4 COMPARISON OF P3 COMPONENTS AMONG PATIENTS WITH PARKINSON'S DISEASE, PATIENTS WITH ALZHEIMER'S DISEASE, AND NORMAL CONTROL SUBJECTS Parkinson'sdisease Alzheimer's Demented (A) Nondemented (B) disease (C) No. of subjects 6 Age(years) 70.74- 11,3 P3alatency(msec) 335.0:1:30.8 amplitude (/tV) 5.3 4. 3.8 P3blatency(msec) 518.3+27.1 amplitnde(/tV) 16.54-11.5 * P < 0.05, ** P < 0.01.

25 66.04- 7.6 321.74.27.5 4.2 4- 2.8 453.24-61.4 16.5+ 6.5

Normal control (D)

9 15 73.64- 8.8 68.74-11.8 402.24.29.1 330.04-29.5 2.5 4- 3.4 3.5 4- 2.8 532.24-39.0 438.74-43.2 11.74. 3.1 13.44- 6.8

F

A/B A / C A / D (Bonferroni's test)

1.42 21.32 ** 2.24 9.12 ** 1.63

**

B/C

** **

*

B/D

C/D

139 TABLE 5

visual P3b latency was comparable to the changes reported previously (1-1.5 msec/year) (Beck et al. 1980; Pfefferbaum et al. 1984; Polich et al. 1985). Although there are still a small number of studies investigating the effect of age on novelty P3 or P3a components, the rate of increase in visual P3a latency (1.00 msec/year) obtained in this study also agrees with previously reported values (1.0-1.7 msec/year) (Polich bt al. 1985; Knight 1987; Yamaguchi and Knight 1991b). We consider these normal aging effects on P3a and P3b latency before discussing results for the Parkinson's and Alzheimer's disease, these being quite relevant. According to the two-process theory of Shiffrin and Schneider (1977), information processing is based on controlled and automatic processing modes. Passive attention automatically induced by rare stimuli can be related to an automatic detection process, whereas active attention directed to target identification in response to task-relevant stimuli is related to a controlled process. From the automatic/controlled viewpoint, P3a corresponds to automatic processing and P3b reflects controlled processing (Ford and Pfefferbaum 1991). Thus, the present results suggest that normal aging affects both automatic and controlled processing. The underlying mechanism of age-related changes in P3a and P3b latency remains unclear. Knight (1987) suggested that both the target and non-target (novelty)

COMPARISON OF P3A AND P3B LATENCIES BY THERAPY GROUPS No. of subjects

P3a latency (msec)

P3b latency (msec)

Anticholinergics 15 + 16

328.7 + 33A 321.9-1-23.4

471.3+ 66.9 460.6+ 58.4

L-Dopa +

323.3 + 12.1 325.6+31.2

486.7 + 103.5 460.84- 49.1

-:

6 25

did not receive; + : did receive.

found to influence latency (Riklan et al. 1976: Frasher and Findley 1991). As shown in Table 5, no significant differences were detected.

Discussion

In the normal subjects of the present study, significant age-related changes in the latency of the P3b component elicited by actively attended target stimuli were noted and also in the latency of the P3a component elicited by task-irrelevant rare stimuli and related to a central nervous system component of orienting response or passive attention (Squires et al. 1975; Knight 1990). The increase (1.40 msec/year) of the

Parkinson's Disease Parkinson's Disease [Jemented Nondemented 64yrs Female 68yrs Female

Normal Subject 62yrs Female

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Fig. 5. Difference waves showing P3a and P3b components in patients with demented and nondemented Parkinson's disease, a patient with Alzheimer's disease and a normal subject. The Alzheimer's disease patient shows prolonged P3a and P3b latency. The patient with demented Parkinson's disease shows prolonged P3b latency and normal P3a latency.

140 P3 components represent neural elements of a common cerebral mismatch detector underlying the orienting response, with the target P3b being generated by active and the non-target P3a being generated by passive engagement of the circuitry that responds during orientation. In agreement with previous studies (Polich et al. 1985; Knight 1987; O'Donnel et al. 1990; Yamagnchi and Knight 1991b), the P3b latency observed here was prolonged relative to that of P3a. This may be related to the interposed decision processes required to identify the stimulus as a target and then orient towards it, as suggested by Knight (1987). In that case, rare non-target stimuli would generate a P3a with no need for an intervening decision process. There is some evidence that dopaminergic system is related to the P3 component (Riklan et ai. 1976; Frasher and Findley 1991; Stanzione et al. 1991). Aging is also associated with loss of nigrostriatal dopaminergic neurons, which is less severe than in Parkinson's disease (McGeer et al. 1988). Parkinson's disease may possibly be an active pathological process superimposed on age-related neuronal attrition of a nigrostriatal system (McGeer et al. 1988). In the present study, patients with nondemented Parkinson's disease showed no differences in P3a and P3b components from age-equivalent normal subjects. This finding agrees with the results of Goodin and Aminoff (1987), who could find no changes in P3b latency in nondemented patients. Our results thus suggest the relative preservation of cognitive information processing with respect to I)3 components in nondemented patients with Parkinson's disease, and in consideration of P3 components, change above the cognitive hypofunction with normal aging may involve a more extensive system as well as the dopaminergic system (Pillon et al. 1989). Patients with demented Parkinson's disease showed increased P3b latency, thus indicating impairment of the attention-controlled processing, while no significant difference was found in P3a components for patients and age-equivalent normal subjects. This indicates the automatic detection stage reflected by the P3a component to possibly be less impaired than the attention-controlled processing reflected by P3b in patients with Parkinson's disease. But it is unclear whether Parkinson's disease with and without dementia represents two separate diseases or extremes of a wide nosological continuum (Hakin and Mathieson 1979; Brown and Marsden 1988; Kawabata et al. 1991). The P3b latency is reported to be increased in patients with dementia, including that due to Alzheimer's disease and Parkinson's disease (Goodin and Aminoff 1986, 1987; Filipovic et al. 1990) and the present results confirmed those of previous studies. In addition, the present study showed no significant difference in P3b latency between the two dementia

groups. These results support the notion (Goodin and Aminoff 1986; Polich et al. 1986) that the degree of prolongation of the P3b latency may be determined by the severity of dementia, since there was no significant difference in its severity of dementia between the Alzheimer's disease and Parldnson's disease groups. The site of generation of the scalp-recorded P3b component still remains unclear, although various sites have been proposed, including sources in the neocortical (McCarthy and Wood 1987), limbic (Halgren et al. 1980), and thalamic (Yingling and Hosobuchi 1984) regions. Likewise, the location of the P3a generator also remains to be determined. Selective abnormalities in P3b latency and a normal P3a latency in demented Parkinson's disease indicate that these P3a and P3b possibly have different generation sites. Extensive bidirectional prefrontal-parietal pathways have been demonstrated anatomically and singie-unit and metabolic studies implicate prefrontal and parietal regions in attention mechanisms (Knight 1987). Using auditory discrimination tasks, Knight (1984) demonstrated that the P3a produced by unexpected deviant stimuli was selectively abnormal in patients with prefrontal lesions. Furthermore, as described in the Introduction frontal lesions have also been implicated in Parkinson's disease by neuropsychological studies (Piccirili et al. 1989; Taylor et al. 1990) and cerebral blood flow studies (Bes et al. 1983). Although these findings might lead us to expect abnormalities in the P3a components in Parkinson's disease, the present study did not show any significant alterations of P3a component even in demented Parkinson's disease. These results may suggest that frontal dysfunction is not always associated with alterations of the P3a component, although differences in the severity and the nature of the cognitive impairment and brain lesions may have existed between Knight's and our study populations. The patients with Parkinson's disease in this study remained on antiparkinsonian medication. The relationship between cognitive function or the P3b component and antiparkinsonian medication is still controversial. Some authors (Riklan et al. 1976; Frasher and Findley 1991; Stanzione et al. 1991) have found an influence of such medication upon cognitive function or the P3b component, but others (Rafal et al. 1984; Goodin and Aminoff 1987; Higasa et al. 1987) did not find any cognitive changes or alterations in P3b latency due to L-Dopa or anticholinergic therapy. Stern et al. (1984) have reported that impairment of attention is closely related to impairment of the noradrenergic system rather than the dopaminergic system. Moreover, in our study, there were no significant differences in amounts of drugs for the nondemented and demented patients. No significant differences were obseved in P3a and P3b latency by the therapy groups. These findings suggest that the effect of antiparkinso-

141

nian therapy upon our results would be slight or nonexistent. In patients with Alzheimer's disease, both automatic rare-stimulus detection and controlled target-identification appear to be impaired, since P3a and P3b latency was significantly prolonged compared to age-related normal decline. Knight (1990) noted a decrease in P3a and P3b amplitudes in patients with temporoparietal lesions. It is also generally accepted that temporo-parietal lesions can be detected by studies of cerebral blood flow and metabolism (Bepson et al. 1983; HeUman et al. 1989; Kawabata et al. 1991) in the early stage of Alzheimer's disease. These findings may be compatible with our present results, which showed prolonged latency of both the P3a and P3b components. Therefore, the human temporo-parietal region may be part of a neural network involved in cognitive functions such as information processing. Our study thus showed some electrophysiological difference between patients with demented Parkinson's disease and those with Aizheimer's disease. These differences seems to be related to the type of dementia itself, since there were no significant differences in P3a and P3b components between patients with nondemented Parkinson's disease and normal controls. Goodin and Aminoff (1986) also found electrophysiological differences between demented Parkinson's disease and Alzheimer's disease: the latency of the N2 and P3b components of auditory ERPs was prolonged in demented patients with Alzheimer's disease and Parkinson's disease, but the N1 latency was prolonged only in the Parkinson's disease patients. However, this was not confirmed by Filipovic et at. (1990), who could not find any difference in N1 latency between patients with demented Parkinson's disease, those with Alzheimer's disease, and normal controls. Whether parkinsonian dementia is separate and distinct from dementia of the Alzheimer type is difficult to decide, but our findings on the P3a component suggests that the automatic rare-stimulus detection process, associated with passive attention, is impaired in Alzheimer's disease but not in demented Parkinson's disease. Impairment of attentional process has been noted in patients with Alzheimer's disease (Baddeley et al. 1986; Spinnler and Della Sala 1988) and Parkinson's disease (Brown and Marsden 1988; Goldenberg 1990). However, it is quite difficult by neuropsychological tests to evaluate the automatic detection process, as was conducted here by an electrophysiological method. Our results in relation to current opinions on cognitive dysfunction in demented Parkinson's disease and Alzheimer's disease cannot be interpreted fully at present. Additional study will be required for this. Aclmowledgements The authors wish to thank Assoc. Prof. T. Okita, PhD, and K. Konishi, MA, of the Department of Science of Behavior for their valuable advice.

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