Semantic Processing in Patients with Alzheimer's Disease. MARILYN ALBERT. Departments of Psychiatry and Neurology, Massachusetts General Hospital,.
BRAIN
AND
LANGUAGE
37, 163-171 (1989)
NOTES AND DISCUSSION Semantic Processing
in Patients with Alzheimer’s
Disease
MARILYN ALBERT Departments
of Psychiatry and Neurology, Massachusetts General Hospital, Division on Aging, Harvard Medical School AND
WILLIAM
MILBERG
Geriatric Research, Education and Clinical Center, Veterans Administration Medical Cen!er
Ten patients with dementia of the Alzheimer type and 10 normal controls performed a lexical decision, semantic facilitation task. The performance of the patients differed from that seen in normals. A post hoc subdivision of the data suggested that the deviation from normality was not uniform throughout the patient population. Six of the 10 Alzheimer patients showed an advantage of related primes over unrelated primes, while 4 of the 10 were actually faster in the unrelated condition than in the related condition. Nevertheless, both groups of Alzheimer patients showed lexical decision latency differences between unrelated and related prime words, suggesting that patients with Alzheimer’s disease are sensitive to the semantic relationships between words. 0 1989 Academic PWS, IX.
There is evidence that many mildly impaired patients with dementia of the Alzheimer type (AD) have deficits in naming ability (Bayles, 1982). Several recent papers have suggested that the most likely explanation for this impairment is that Alzheimer’s disease produces deficits in the semantic representation of words, i.e., the stored associative network of word meaning (Schwartz, Marin, & Saffron, 1979; Grober, Buschke, Kawas, & Fuld, 1985; Martin & Fedio, 1983). However, Nebes, Martin, and Horn (1984) showed that in a simple word reading paradigm, reading latencies for both AD patients and controls This work was supported in part by Grants ROl-AGO3354 and POl-AGO4953 from the National Institute on Aging and Grant 097443765from the Veterans Administration. Address reprint requests to Dr. Marilyn Albert, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114. 163 0093-934X/89 $3.OO Copyright B 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
164
NOTES AND DISCUSSION
were shorter when target words were immediately preceded by related words than when target words were preceded by unrelated words. Thus, Nebes et al. concluded that the requisite semantic information needed to facilitate word reading was present in patients with Alzheimer’s disease. If semantic processing is, indeed, intact in AD patients, one would expect that other paradigms that assessthe underlying aspects of language function would also be preserved in Alzheimer’s disease. One such task is the lexical decision paradigm (Meyer & Schvaneveldt, 1971). It has been used to demonstrate that even stroke patients who cannot read simple words aloud can be sensitive to the semantic association between words (Milberg & Blumstein, 1981). Therefore the present study was carried out in order to determine whether observations of preserved semantic processing in AD could be extended to the lexical decision paradigm. The lexical decision paradigm shares with the reading paradigm the characteristic of passive sensitivity to semantic structure. METHODS Subjects. Study participants included 10 AD patients (7 male, 3 female) and 10 normal controls (NC). The participants ranged in age from 61 to 85 years of age. The mean age of the AD patients was 74.5 and the mean age of the controls was 68.8. No significant difference in age was detected between the two groups (t < I). The diagnosis of Alzheimer’s disease employed NINCDS-ADRDA criteria for probable Alzheimer’s disease (McKhann et al., 1984)and was based on the judgment of a neurologist, psychiatrist, and neuropsychologist. Medical conditions known to produce dementia were excluded and only patients who received an ischemic score of 4 or less (Hachinski, 1978) were included. The degree of impairment of the patients was operationally defined on the basis of the patient’s performance on the Mattis Dementia Rating Scale (Mattis, 1976). Patients had Dementia Rating Scale scores of 107 to 140 with a mean of 119.5. The group, therefore, included patients who were mildly impaired. The controls were healthy adults who were members of the Normative Aging Study at the Boston Veterans Administration Outpatient Clinic. Lexical decision procedure. Stimuli consisted of pairs of real words and nonwords in which the first member of the pair was considered the prime and the second member the target. Four types of word pairs were used representing two priming conditions for the real words (YES responses), and two priming conditions for the nonwords (NO responses). The first condition consisted of 1.5real word monosyllable targets preceded by a related word (e.g., dog-cat); the second consisted of 15 real word targets preceded by an unrelated word (e.g., land-cat). The last two types of word pairs consisted of 15 nonword targets preceded by a real word (e.g., day-colp) or 15 nonword targets preceded by a nonword (kemon-ank). The related words were chosen from the Connecticut Free Association Norms (Bousfield, Cohen, Whitmarsh, & Kinkaid, 1961).The nonword stimuli were versions of the real word stimuli converted into pronounceable nonwords by changing one letter (e.g., lion to mion). The stimuli in this study were similar to those used in previous studies of lexical decision (Milberg & Blumstein, 1981), with the exception that a semantically neutral baseline was eliminated to minimize the number of experimental trials. The stimulus pairs were randomized and presented on an Apple II Computer on a standard screen. Subjects sat approximately 45 cm from the screen so that the stimuli
NOTES AND DISCUSSION
165
subtended from 4” to 6” of visual angle. Trials and conditions were randomized for each subject. Primes were presented for 1000 msec, followed first by a 500-msec interval, and then the presentation of the target word, which appeared on the screen until the subject responded. Subjects responded by pressing one of two telegraph keys; they were marked YES and NO. The subjects were asked to press the YES key when the second word was a real word and the NO key when the second word was a nonword. Thus, for the first two priming conditions (i.e., real word-real word and nonword-real word) the correct response was YES. For the second two priming conditions (i.e., real word-nonword and nonword-nonword) the correct response was NO. Reaction times were based on the interval between the onset of the target and the subject’s response. Timing accuracy was kept within a 2 17-msec tolerance with a synchronized Mountain Clock.
RESULTS AND DISCUSSION
Reaction time data were subjected to a logarithmic transformation (base 10) prior to analysis, due to the wide discrepancy in the mean and variance of the reaction times of the AD patients and controls. The data were analyzed with repeated measures analysis of variance (ANOVA) and correlational procedures. Unless otherwise specified, all analyses were based on the mean latencies of correct lexical decisions. Reaction times of the normal controls were shorter than those of the AD patients in the YES condition (F(1, 18) = 5.92, p s .03). Although the overall effect of Prime Type was not significant (F s l), the Group by Prime Type interaction was significant (F(1, 18) = 19.62, p s .OOl). Post hoc comparisons showed that, for the normal controls, the reaction times for real word targets preceded by a related word were shorter than when real word targets were preceded by an unrelated word (F( 1, 9) = 13.64, p < .005). In contrast, there was no difference in reaction time between related and unrelated priming conditions for the AD group (F( 1, 9) = .26, p = 1). These results are shown in Table 1. The AD patients were also slower than the controls in the NO condition (F(1, 18) = 6.63, p d .05). The AD patients’ mean latency for correct lexical decisions to nonwords was 1667 msec; the controls’ mean correct NO decision latency was 929 msec. There was no effect of real word vs. nonword prime type in the NO condition (F(1, 18) = 2.46, p 3 .lO). TABLE
1
MEAN REACTION TIME OF AD PATIENTS AND CONTROLSON A LEXICAL DECISION TASK”
Prime type Group
Related word
Unrelated word
Controls AD patients
582.3 f 80.8 944.3 + 423.4
621.9 t 88.6 986.7 2 536.8
a msec.
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NOTES AND DISCUSSION
Few errors were made by subjects in either group in the YES condition, though the AD patients made more errors than the normal controls (0.85 vs. 0.10 errors, respectively) (F(1, 18) = 4.86, p < .OS).The lack of an error main effect for Prime Type (F(1, 18) = .03, p 3 SO) and the lack of an error Prime Type by Group interaction (F(1, 18) = .67, p 2 .lO) suggested that errors were so rare that it was unlikely that they affected the experimental results. Neither of the groups made errors in the NO condition. Thus, the controls showed a semantic facilitation for real words preceded by a related word but semantic content did not appear to affect nonword decisions. These data are therefore similar to those reported for both young and old subjects in several other laboratories (Cerella & Fozard, 1984; Bowles & Poon, 1981). The AD patients as a group did not appear to show sensitivity to the semantic characteristics of words by responding more quickly to target words preceded by real words than target words preceded by unrelated words. However, an inspection of the distribution of difference scores for the individual subjects indicated that the pattern of performance for the AD patients was different from the pattern of performance of the control subjects. Of the 10 AD patients tested, 6 showed the typical semantic facilitation effect seen in normal subjects. For these subjects (Group I), the average reaction time advantage of the related over unrelated condition was 194 msec (See Fig. 1). There was a significant difference between the speed of response to the related vs. the unrelated words (t(5) = 2.65, p s .04). In contrast, the average reaction time for four of the 10 AD patients (Group 2) was 193.8 set longer in the opposite direction, i.e., the reaction time advantage was for the unrelated over the related condition. This difference was also significant (t(3) = 6.82, p s .006). Only 1 of the normal control subjects showed a slight negative priming effect (see Fig. 1). A two-way analysis of variance (ANOVA) was then conducted to compare the performance of Group 1 (the primers) to Group 2 (the negative primers) for correct lexical decisions (the YES condition). The overall effect of Group was not significant (F(1, 8) = 10.14, p d .9), but the Group by Prime Type effect was significant (F( 1, 8) = 21.15, p c .002). These results are summarized in Fig. 2. It should be noted that the primers and negative primers did not differ from each other in the number of real word lexical decision errors they made (F(l) 8) = .05, p 3 .lO), nor did they show a Prime Type (F(1, 8) = .15, p s .lO), or a Prime Type by Group interaction (F(1, 8) = .15, p 3 .lO) for errors in the YES condition. The reaction time of the primers in the NO condition did not differ from that of the negative primers (F(1, 8) = .02, p 1 .5). The primers mean latency for correct lexical decisions to nonwords was 2082 msec; the negative primers mean correct NO decision latency was 2377 msec.
167
NOTESAND DISCUSSION
W Alzheimer’s
h (I) E
400
ii
200
.-2 z
0
.k
ii
a
-200
-400
l I2
3
4
5
Subject
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7
8
9
IO
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E
200
F .-E c 0
a:
0
-200
-400 I
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FIG. 1. Difference scores between related and unrelated primes in the YES condition for individual subjects in the control group and the Alzheimer group.
There was no effect of real word vs. nonword prime type in the NO condition (F(1, 8) = 3.3, p c .ll). The size of the difference between the related and unrelated priming conditions was then correlated with two clinical measures that are usually thought of as being sensitive to general semantic competency, the Boston Naming Test (Kaplan, Goodglass, & Weintraub, 1983) and the logical memory subtest of the Wechsler Memory Scale (WMS) (Wechsler, 1945). Though control subjects showed a small relationship between performance on the two tasks and the priming condition differences (r = .32, Y =
168
NOTES AND DISCUSSION
2000 W Related ffl Unrelated
1000
0 Group
Group
1
Alzheimer’s
2
Group
FIG. 2. The speed of response to related vs. unrelated words in the lexical decision task by the six AD patients who showed a positive priming effect (Group I) and the four AD patients who showed negative priming (Group 2).
.35, respectively) the correlations were not significant (p = .37, p = -31, respectively). For the AD patients there was also no indication of a relationship between performance on either clinical variable and priming differences (r = .08, p = .83; r = .03, p = .93). An analysis was also conducted to compare the overall level of cognitive dysfunction in the two groups of AD patients. There was no correlation between performance on the Dementia Rating Scale (DRS) and the size of the difference between the related and unrelated priming conditions for either Group 1 (u = .20, p = .69) or Group 2 (r = .89, p = .I 1). The size of the correlation for Group 2, however, suggested that the lack of significance might be related to the small sample size. Therefore a t test comparing the DRS scores of the two groups was carried out. It showed a significant difference between Group 1 and Group 2 (t(8) = 2.36; p < .05). Group 2, the negative primers, was more impaired than Group 1.
NOTES AND DISCUSSION
169
Because of the surprising finding of “negative priming” in the AD patients it was felt that a measure of within-subject consistency of priming would be of use in evaluating the subjects’ ability to use lexical information. This is especially important since it is possible that the analysis based on group means may have obscured an anomalous or inconsistent performance by individual subjects. For this purpose, a consistency measure was developed for each subject based on the percentage of correct trials in which the related primes resulted in longer reaction times than the unrelated primes (i.e., the percentage of “negatively” primed trials for each subject). Arc sin transformations for proportional data were used for the statistical analysis. Negative priming was observed in 51.5% of the related-unrelated pairs for the AD patients and 38.3% of the relatedunrelated pairs for the normal controls. This difference was significant (t = 2.06, p = .OS). Interestingly, using this measure of consistency of “negative priming,” the AD patients who were classified as “negative primers” on the basis of mean reaction time scores did not differ from AD patients who were classified as “positive primers” (53.5% vs. 50.5%, respectively; t = .394, p = .7041). A correlational analysis demonstrated that, for the normal controls, the consistency of negative priming measure was not significantly correlated with performance on the Dementia Rating Scale (r = .29). However, unlike the correlational analyses based on mean reaction times described above, for the AD patients, there was a significant correlation between consistency of negative priming and Dementia Rating Scale score (r = .87, p = .002). Scores on the Wechsler Memory Scale and the Boston Naming Test were not significantly correlated for either group (r = .23 and r = .46), respectively, for the controls and r = .58 and r = .lO, respectively, for the patients). These data indicate that the performance of AD patients on a semantic facilitation task differs from that seen in normals. However, the deviation from normality is not uniform throughout the patient population. One group of patients (Group l), though showing the typical advantage of related primes over unrelated primes, produced an average effect that was larger than that observed in normal subjects. It should be noted that three of the patients in this group appeared to show priming effects similar in size to those of the normals. On the other hand, patients in Group 2 were actually faster in the unrelated condition than in the related condition and therefore produced an effect that was opposite to that of the normal controls. The performance of both groups, in terms of overall reaction time, was equivalent. Although this subdivision of subjects must be considered preliminary because of the small sample size, these results suggest that both groups of AD patients (i.e., the primers and the negative primers) are sensitive to the semantic relationships between words, since all patients show a
170
NOTES AND DISCUSSION
difference between related and unrelated words. This result is consistent with the conclusion of Nebes et al. (1984) that the semantic associative network is at least grossly intact in AD patients, permitting them to identify words within a semantic field to one another. However, the fact that some patients show an exaggerated priming effect while others show the opposite (i.e., a negative priming effect) suggests that access to semantic information can be impaired in patients with Alzheimer’s disease. The phenomenon of negative priming in AD is particularly unusual. One can speculate it may be parallel to a recent observation in normals showing that negative priming occurred when subjects were asked to ignore a semantically related word or object in a prime display (Tipper, 1985). Tipper argued that internal representations of the ignored object became associated with inhibition, thus slowing access to the subsequent target. Ober, Dronkers, Koss, Delis, & Friedland (1986) used a similar argument to explain their finding that AD patients showed negative priming in a word retrieval task. It is important to note that Wernicke aphasics, who show severe deficits in language comprehension, show normal semantic facilitation effects and have never been reported to show large negative priming effects (Milberg & Blumstein, 1981). The difference between the performance of stroke patients and those with AD suggests that dementing disorders may have a different effect on the CNS than do pathologies that produce focal cognitive deficits, such as stroke. REFERENCES Bayles, K. A. 1982. Language function in senile dementia. Bruin and Language, 16, 265280. Bousfield, W. A., Cohen, B. H., Whitmarsh, G. A., & Kinkaid, W. D. l%l. The Connecticut Free Association Norms (Report No. 35). Storrs, CN: Department of Psychology. Bowles, N. L., & Poon, L. W. 1981. The effect of age on speed of lexical access. Experimental
Aging Research,
7, 417-426.
Cerella, J., & Fozard, J. L. 1984. Lexical access and age. Developmental Psychology, 20, 235-247. Grober, E., Buschke, H., Kawas, C., & Fuld, P. 1985. Impaired ranking of semantic attributes in dementia. Brain and Language, Xi, 276-286. Hachinski, J. 1978. Cerebral blood flow differentiation of Alzheimer’s disease from multiinfarct dementia. In R. Katzman, R. Terry, & K. L. Bick (Eds.), Alzheimer’s disease: Senile dementia and related disorders. New York: Raven Press. Pp. 97-104. Kaplan, E., Goodglass, H., & Weintraub, S. 1983. The Boston Naming Test. Philadelphia: Lea & Febiger. Martin, A., & Fedio, P. 1983. Word production and comprehension in Alzheimer’s Disease: The breakdown of semantic knowledge. Bruin and Language, 19, 124-141. Mattis, S. 1976.Dementia rating scale. In R. Bellack & B. Karasu (Eds.) Geriatric psychiatry. New York: Grune & Stratton. Pp. 108-121. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. 1984. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology, 34, 939-944.
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Meyer, D. E., & Schvaneveldt, R. W. 1971. Facilitation in recognizing pairs of words: Evidence of a dependence between retrieval operations. Journal of Experimental Psychology,
90, 227-234.
Milberg, W., & Blumstein, S. 1981. Lexical decision and aphasia: Evidence for semantic processing. Brain and Language, 14, 371-385. Nebes, R. D., Martin, D. C., & Horn, L. C. 1984. Sparing of semantic memory in Alzheimer’s disease. Journal of Abnormal Psychology, 93, 321-330. Ober, B. A., Dronkers, N. F., Koss. E., Delis, D. C., & Friedland. R. P. 1986. Retrieval from semantic memory in Alzheimer-type dementia. Journal of Cliniurl and Experimen&d Neuropsychology,
8, 75-92.
Schwartz, M. F., Marin, 0. S. M., & Saffran, E. M. 1979. Dissociation of language function in dementia: A case study. Brain and Language, 7, 277-306. Tipper, S. P. 1985. The negative priming effect: Inhibitory priming by ignored objects. Quarterly Journal OfExperimental Psychology: Human Experimental Psychology, 37A, 571-590. Wechsler, D. 1945. A standardized memory scale for clinical use. Journal of Psychology, 19, 87-95.
