Brain, Vol. 124, No. 8, 1522-1532,
August 2001
© 2001 Oxford University Press
The nature of semantic memory deficits in Alzheimer's disease
New insights from hyperpriming effects
1 INSERM U320, Laboratoire de Neuropsychologie, CHU Côte de Nacre, 14033 Caen cedex and 2 Clinique Neurologique, Centre de la Mémoire, CHRU, Hôpital Roger Salengro, 59037 Lille, France
Correspondence to:
Professor Francis Eustache, INSERM U320, Laboratoire de Neuropsychologie, CHU Côte de Nacre, 14033 Caen Cedex, France E-mail: neuropsycho{at}chu-caen.fr
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Abstract |
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While semantic memory deficits are a common landmark of Alzheimer's disease, the nature of these impairments remains to be clarified. Implicit tasks which assess semantic priming effects are often used to understand semantic deficits in Alzheimer's disease, but they have led to unclear conclusions because of methodological problems such as intervention of attentional mechanisms. To explore the effects of semantic priming in Alzheimer's disease and their relationship with semantic memory deficits, we used two tasks, one implicit and the other explicit. The implicit task was a lexical decision task to assess semantic priming, and in which pairs of words had coordinate (tiger–lion) or attribute relationships (zebra–stripe). The explicit task was a semantic knowledge task composed of namings and questions involving superordinate categories and attribute knowledge of concepts. The two tasks systematically assessed the integrity of the same concepts. This protocol was given to 53 Alzheimer's disease patients with mild to moderate dementia and to 20 controls. The Alzheimer's disease group as a whole obtained significantly greater priming effects (hyperpriming) than controls in the coordinate condition, and equivalent priming in the attribute condition. In the coordinate condition, a subgroup of 26 patients, with attribute knowledge deficits, had larger priming effects than both a subgroup without semantic deficits and the control group. These results show that in Alzheimer's disease the semantic priming effects vary according to the degree of attribute loss, and the presence of hyperpriming would reflect semantic memory deficits. This study unravels the fine-grained structure of semantic memory disturbances in Alzheimer's disease with mild to moderate dementia, affecting initially the attributes of concepts within a hierarchical network in which superordinate concepts remain preserved.
Alzheimer dementia; semantic memory; semantic priming; hyperpriming
ANOVA = analysis of variance; DRS = dementia rating scale; MMSE = Mini-Mental State Examination; SOA = stimulus–onset asynchrony
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Introduction |
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Patients with Alzheimer's disease can be affected, in the beginning of the dementia, by semantic memory disorders causing semantic paraphasias or superordinate responses to object naming tasks (Martin and Fedio, 1983
; Kirshner et al., 1984; Huff et al., 1986; Hodges et al., 1992), or by low production of items from a given semantic category on timed verbal fluency tasks (Ober et al., 1986; Troster et al., 1989; Bayles et al., 1990; Hodges and Patterson, 1995). Despite the unequivocal evidence of semantic deficits in Alzheimer's disease, questions related to the nature of these disturbances have not been satisfactorily answered. A controversy remains as to whether the semantic deficit stems from a loss of information in the semantic store (Chertkow et al., 1989, 1994; Chertkow and Bub, 1990; Hodges et al., 1992; Martin, 1992; Chan et al., 1993, 1995; Randolph et al., 1993; Binetti et al., 1995), or whether the store of semantic memory remains intact in Alzheimer's disease, and the deficit is related to a disturbance in an Alzheimer's disease patient's ability to access and manipulate semantic information (Ober and Shenaut, 1988; Nebes, 1989, 1992, 1994; Nebes et al., 1989; Bayles et al., 1991; Hartman, 1991). However, the tests often used to explore the semantic memory are not specific and involve cognitive processes, other than semantic processing, which are often disturbed in Alzheimer's disease (working memory, attentional resources and strategy implementation).
A number of authors have used the semantic priming paradigm to assess the integrity of the semantic memory network in Alzheimer's disease. This paradigm allows one to assess the semantic memory implicitly and then to minimize the intervention of non-semantic cognitive processing. Priming effects correspond to the modification of a stimulus processing behind the presentation of the same stimulus or a related stimulus. Semantic priming effects depend on semantic memory (Tulving, 1995), and require a semantic processing of the prime stimulus and/or a semantic relationship between the prime and the target. In normal individuals, many studies on semantic priming effects report that, in lexical decision or pronunciation tasks, recognition of a target word (chair) is facilitated by the prior presentation of a related prime word (table) compared with an unrelated control word (horse) (Meyer and Schvaneveldt, 1971; Fischler, 1977; Neely, 1977). The subject does not make explicit judgement on the link between the prime and the target, and this processing facilitation is thus supposed to depend on an automatic access to information. Those priming effects are commonly viewed, within the framework of the automatic spreading activation in the semantic network, as a pre-activation of the target by a related prime (Collins and Loftus, 1975): the presentation of a prime (word or picture) automatically activates its node in memory; this activation spreads to highly related nodes, thus momentarily increasing their accessibility.
Semantic priming effects have been investigated in patients with Alzheimer's disease by a number of authors, often with conflicting results. Some authors report less-than-normal priming (Ober and Shenaut, 1988; Salmon et al., 1988; Silveri et al., 1996), others report equivalent priming for Alzheimer's disease patients and normals (Nebes et al., 1984; Ober et al., 1991) or increased priming (hyperpriming) in Alzheimer's disease patients (Chertkow et al., 1989, 1994; Nebes et al., 1989; Balota and Duchek, 1991; Hartman, 1991; Margolin et al., 1996; Balota et al., 1999, Experiment 1). These conflicting results are partly due to the use of different experimental procedures, at the task level (lexical decision task or pronunciation task) as well as at the processing level (intervention or not of attentional mechanisms) (see Glosser and Friedman, 1991). Moreover, the severity of the dementia of the patients is different from one study to another.
Conflicting hypotheses have been advanced to explain the hyperpriming effect. According to Chertkow and colleagues, it is mainly due to a degradation in semantic storage: hyperpriming was particularly evident for those items that had been found degraded in explicit semantic tasks in the same patients (Chertkow et al., 1989). The words for which the patients had intact semantic knowledge did not show hyperpriming, but equivalent priming effects for patients and controls. Moreover, when one considers the complexity of the conceptual structure, the presence of semantic priming does not necessarily mean that the semantic representations of concepts are entirely preserved (Moss et al., 1995a; Nakamura et al., 2000). General and specific semantic information is supposed to be stored at different levels in hierarchical models of semantic memory (Collins and Quillian, 1969). In the case of a semantic loss, specific information represented at lower hierarchical levels could therefore be disrupted, in spite of the integrity of general information represented at higher superordinate level. Besides, apparently normal priming effects may reflect partial semantic degradation; damage to stored representations may result in loss of some, but not all, of the specific attribute information. In this case, semantic priming effects, supported by the remaining intact features only, can be observed. Martin (1992) adds that hyperpriming would specifically reflect a storage deficit for specific attributes which are essential for distinguishing between conceptually similar concepts: because similar concepts are difficult to tell apart for the patients (since they belong to the same preserved superordinate category and consequently share a large number of the same preserved features), hyperpriming would become comparable with a repetition priming, in which the prime and the target are the same and in which the magnitude is greater than the one of the semantic priming. On the contrary, Nebes and colleagues view hyperpriming as proof of a structurally intact semantic store which would only be accessible in an automatic and unconscious way, and would mainly reflect an artefact of a general slowing in Alzheimer's disease: the slower the patient responds, the larger semantic priming effects he shows (Nebes et al., 1989). For other authors (Hartman, 1991; Ober et al., 1991; Ober and Shenaut, 1995; Silveri et al., 1996), hyperpriming may just occur in some experimental conditions which incite the subject to develop attentional strategies, such as expectancy mechanisms or postlexical semantic matching processes (for review, see Neely, 1991), and which are deficient in Alzheimer's disease. The expectancy mechanism, which is itself a prelexical process, is under the strategic control of the subject. It accounts for the priming effects by assuming that the subject uses the prime to generate an expectancy set that consists of potential targets that are related to the prime: if the subject remarks that the prime is sometimes followed by a related word, he can try to guess what the target will be. This mechanism facilitates the processing of expected targets, and inhibits the recognition of unexpected targets. It occurs with relatively high proportions of related pairs, with a long time relationship between the onset of the prime and the target [stimulus–onset asynchrony (SOA)]. The postlexical semantic matching process occurs after the appearance of the target if the subject notices that there is a semantic relationship between the prime and the target. As such, he will be biased towards a `word' response (no relationship would be remarked if the target was a non-word). Thus, the subject answers more easily that the target is a word when related to the prime. On the other hand, inhibitory effects occur if he notices no semantic relationship; he would tend to answer that the target is a non-word, and this would slow down his `yes' response, especially if the non-word ratio is high (Neely et al., 1989).
These explanations for hyperpriming through the influence of cognitive slowing or by the intervention of attentional mechanisms may partially explain the results observed in the literature. Nevertheless, the degraded semantic store hypothesis, as suggested by Chertkow and colleagues and Martin, deserves interest and merits testing with a carefully constructed protocol (Chertkow et al., 1989; Martin, 1992). In the present study, we controlled for the effects of cognitive slowing, which characterizes Alzheimer's disease patients and older subjects in general, with the help of a measurement expressed as a percentage of the priming effects. Moreover, we minimized the intervention of attentional mechanisms with the help of automaticity criteria: low proportion of related words (
20%), short SOA (250 ms), low attention to the prime (the subject just had to answer the target) and the same proportion of word targets and non-word targets (Posner and Snyder, 1975; Neely, 1991). It was also necessary to take into account the Alzheimer's disease semantic deficit variability which can hide different semantic priming profiles (see Albert and Milberg, 1989): a study taking into account the performance levels with semantic knowledge could allow a better understanding of the observed priming effects.
The goal of the present study was to clarify the relationships between hyperpriming and semantic memory deficits, and to highlight the nature of semantic disorders in Alzheimer's disease. To assess the semantic memory in subjects with Alzheimer's disease, we compared their performances in two tasks, one implicit and the other explicit. These two tasks used the same stimuli targets. The implicit semantic memory task was a lexical decision task and assessed the semantic priming effects. Warrington and Shallice proposed that the preservation of superordinate information with loss of subordinate knowledge represents one of the criteria for semantic storage disorder (Warrington and Shallice, 1979). For this reason, in the lexical decision task, we used two types of word pairs, some were related according to a coordinate condition (tiger–lion) in which the prime and the target belonged to the same semantic category and shared the same semantic level, and others according to an attribute condition (tiger–stripe) in which the target was a specific attribute of the prime concept. The explicit semantic memory test was a semantic knowledge task inspired by Martin (1987) and Desgranges et al. (1996). This task required decisions involving an active and conscious exploration in semantic memory and was designed to probe for knowledge across the hierarchy of semantic memory from the superordinate to the fine-grained subordinate level.
We made the assumption that the profile of the semantic priming effects evolves as the semantic memory deterioration advances (see Chertkow et al., 1990). Therefore, it was essential to control the degree of semantic deficits with the help of the semantic knowledge task. Thus, considering the progressive deterioration of semantic representations in the case of a deficit storage, hyperpriming would only occur at the onset stage of semantic impairment, and only for the words with a coordinate relationship. At the beginning of the semantic deterioration, some specific features are lost, whereas the superordinate categories are preserved. For example, the tiger and the lion are still known to be wild animals, but knowledge about their stripes and mane, respectively, is lost, which impairs the ability to distinguish between these two very similar concepts. This is the reason why, in the case of a coordinate relation (tiger–lion), not only do priming effects exist—since the words are semantically related through membership in their preserved superordinate class—but they are greater than in a control group (hyperpriming): specific attributes which characterize each concept are lost, hence a confusion, an overlapping between the two coordinate concepts (both are wild animals, and also both have fur and are dangerous). Therefore, the semantic priming (tiger–lion) would be treated by the patient as repetition priming (wild animal–wild animal) in which the magnitude is greater than the former. In an attribute condition (tiger–stripe), the priming effects should decrease or even be absent because knowledge of the specific attributes (stripe) is lost. Therefore, for the patient, there is no longer a link between the words tiger and stripe, and the attribute condition becomes comparable with an unrelated condition (tiger–hammer).
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Subjects
Fifty-three Alzheimer's disease patients with mild to moderate dementia and 20 healthy volunteers were examined. All subjects gave informed consent to the neuropsychological procedure, which was approved by the Ethical Committee of the University of Caen. The patients (mean age 72.9 ± 6.5, range 47–85 years; 17 male and 36 female), all right-handed, were suffering from probable Alzheimer's disease, the diagnosis being made according to the criteria of McKhann and colleagues (McKhann et al., 1984
). All patients underwent a neurological examination, standard laboratory studies, EEG and an extensive routine neuropsychological assessment. No abnormality other than atrophy was found on the CT-scan or MRI. The patients had no previous neurological or psychiatric history. The score for the Mini-Mental State Examination (MMSE; Folstein et al., 1975) was 14–27 (22 ± 3.4) and for the Dementia Rating Scale (DRS; Mattis, 1976) it was 95–136 (118.1 ± 8.7). Control subjects (mean age 70.6 ± 5.8, range 63–86 years, eight male and 12 female) were recruited in clubs for retired people. They had no neurological or psychiatric disorders. The score for the MMSE was 27–30 (28.7 ± 1.1), and for the DRS it was 135–143 (138.5 ± 2.4).
The two groups were paired according to their level of education: the minimum level was equivalent to `certificat d'études primaires'—a diploma generally obtained at ~14 years of age, after 8 years of primary education.
Lexical decision task
Stimuli
There were 30 related pairs of words: 20 pairs of words associatively and semantically strongly related and of the same semantic level (coordinate relation; tiger–lion); and 10 pairs of words, also strongly associated, in which the target was a specific attribute of the prime (attribute relation; zebra–stripe). These pairs were drawn from word association norms (Oléron and Legall, 1962; Rosenzweig, 1970; Lieury et al., 1976). We showed to 100 young subjects 60 of the first written words stemming from those norms; for each of them, they had to give the first word that came to mind. From the pairs of words thus obtained, we selected 30 homogeneous words according to the association frequency. The nouns, which were all concrete and imageable, were three to 10 letters long, and the mean lexical frequency was 60 per million (Brulex; Content et al., 1990). In the two sets of pairs, the words were balanced in terms of length (coordinate 6.1 letters; attribute 5.3 letters), lexical frequency (coordinate 75 per million; attribute 82 per million) and association frequency (coordinate 43%; attribute 47%) with no extreme value in any condition. The semantically related pairs were also associated because the associative strength is an important determinant of the amount of priming (Moss et al., 1995b). To ensure that any priming for a patient with semantic memory damage cannot be attributed to the frequency of a co-occurring word, the association frequency was never maximal and was the same in both related conditions.
The 30 related pairs were included in a list of 300 pairs. All the primes were words. In order to minimize the intervention of postlexical attentional processes, the likelihood of encountering a word versus a non-word in the target position was 50%. Among the pairs in which the target was a word, 20% were semantically related (coordinate or attribute condition) and 80% shared no semantic or associative link, which helps prevent the subject's expectancy about the nature of the target. The non-words, which were all pronounceable, were created by replacing one letter per syllable of a concrete word taken from the word association norms.
The task was divided into four blocks lasting ~5 min each and separated by a few minutes interval. The distribution of these pairs (coordinate, attribute, unrelated words and word/non-word) was realized in the same way in the four blocks. In each block, the pseudo-randomized distribution of the stimuli was the same for all subjects and respected the following constraints: there were never more than five occurrences of word or non-word targets in a sequence, the related pairs never occurred at the beginning of a block and never occurred one next to another.
Procedure
The task was computerized and visual, and was run individually. Stimuli were presented using the software Superlab 1.68 (Cedrus Corporation, Phoenix, Ariz., USA) which allows response times to be measured accurately to 1 ms. All stimuli were centred on the screen and were 2 cm high.
During a trial, the subject saw on the screen a fixation point lasting 500 ms followed by a prime word for 200 ms. Thereafter, the screen remained empty for 50 ms; the SOA was 250 ms, which was too short for the subject to anticipate the nature of the target. Subsequently, the target stimulus appeared and remained visible until a response was made. Then, the screen was empty for 1500 ms and another trial appeared. In order to favour the automaticity of the task, each subject was instructed to respond for the target only: if he recognized, in the series of letters, a French word, he had to press, as fast as possible, the `yes' key with his dominant hand. If the series had no meaning for him, he pressed the `no' key with his other hand.
In order to familiarize the subject with the task, a list of 30 practice trials (unrelated word pairs and word/non-word pairs) was given.
Priming effects, based on differences of response times (mean response times for the unrelated condition – mean response times for the related condition), are expressed as a percentage for each subject (priming effect divided by mean response times for the unrelated condition x 100); this approach helps to prevent a slowing effect on the priming effects. The lexical decision task was always given first in the study.
Semantic knowledge task
This task, drawn from a protocol of Martin (1987) and Desgranges et al. (1996, 1998), was composed of three parts: naming, categorical knowledge and attribute knowledge of concepts. The task involved 30 concepts belonging to four categories (animals, plants, objects and body parts), and corresponding to the related words (coordinate and attribute conditions) in the lexical decision task.
First, we asked the subject to name 30 drawings (corresponding to the 30 concepts). If he failed, a recognition task of the noun was carried out: the correct noun and three others from the same semantic category were presented to the subject one after the other. Then, the subject was asked to answer a series of questions for each of the 30 items. The first questions concerned the knowledge of the superordinate category (`Does it occur naturally or is it man-made?'). The second questions concerned category membership (`Is it an animal, a plant, an object, or a body part?'). The third questions referred to the subcategory (`Is it a domestic or a wild animal?'). Finally, there were three questions concerning specific attributes: either functional (`Is it edible?'), or perceptive (`Does it have a mane?'). The score was the total number of correct answers, the maximum being 236.
Statistical analyses
Non-paired Student's t-tests were carried out in order to compare the demographic data of the groups of subjects. We used analysis of variance (ANOVA) with repeated measures in order to compare the performances for the lexical decision and the semantic knowledge tasks obtained by the groups of subjects. Within each group of subjects, the mean response times and priming effects in the two related conditions were compared with paired Student's t-tests. To investigate the relationships between semantic priming effects and response times, between semantic priming effects and dementia severity index, and between semantic priming effects and semantic knowledge, we used Pearson correlations.
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Demographic data
There was no significant difference in age [t(71) = 1.38, P = 0.17], in educational level [t(71) = 0.951, P = 0.34] or in sex distribution [t(71) = 0.629, P = 0.53] between the two groups of subjects.
Lexical decision task
Accuracy data and response times
In keeping with other studies on semantic priming effects in Alzheimer's disease (Ober et al., 1991; Chertkow et al., 1994), we will report only results for `yes' responses (Table 1). The errors of the patients, which were in most cases immediately self-corrected, were only 2.11%, and were not significantly more than those of the controls [t(71) = 1.76, P = 0.24]. Likewise, in order to ensure that the performances were not influenced by extreme scores, in each condition, response latencies exceeding 3 SD (standard deviations) above each participant's mean were treated as outliers, and the mean was calculated again. Mean reaction times for the correct responses were submitted to a two-way ANOVA with repeated measures: two groups (Alzheimer's disease and controls) x three conditions (coordinate, attribute and unrelated). The results showed a significant effect of group [F(1,71) = 24.17, P < 0.0001] indicating that the response times of the Alzheimer's disease patients were globally longer than the control group. The analysis also showed a significant effect of condition [F(2,71) = 73.47, P < 0.0001]: in the two groups of subjects, the responses in the experimental conditions were faster than in the unrelated condition. The interaction (group x condition) was also significant [F(2,71) = 9.66, P = 0.0001], and is explained by the fact that the response times of the patients were longer in the attribute condition than in the coordinate condition [t(52) = –3.184, P = 0.003], whereas the controls showed the opposite profile [t(19) = 2.263, P = 0.036].
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Semantic priming effects
The significant difference between unrelated and related conditions (both coordinate and attribute) testifies to the presence of semantic priming effects in the two groups of subjects.
A two-way ANOVA with repeated measures: two groups (Alzheimer's disease and controls) x two conditions (coordinate and attribute), showed neither a significant group effect [F(1,71) = 2.44, P = 0.12], nor a condition effect [F(1,71) = 0.06, P = 0.81]. On the other hand, the interaction group x condition was significant [F(1,71) = 11.68, P =0.001]: a non-paired Student t-test indicated that the Alzheimer's disease patients showed, in the coordinate condition, a larger amount of semantic priming than did the control subjects (11.28% versus 6.88%) [t(71) = 3.334, P =0.001]. In the attribute condition, the priming effects in the Alzheimer's disease patients and the control subjects did not differ significantly (8.94% versus 9.58%) [t(71) = 0.433, P = 0.67].
In the Alzheimer's disease group, a paired Student's t-test showed larger priming effects in the coordinate condition than in the attribute condition [t(52) = 2.936, P = 0.005]. Conversely, the control group obtained larger priming effects in the attribute than in the coordinate condition [t(19) = –2.372, P = 0.03].
Correlations between semantic priming effects and response times
In the Alzheimer's disease group, to confirm the absence of slowing effects on the semantic priming effects, we used Pearson correlations between semantic priming effects in the two related conditions, and mean response times in the unrelated condition. The results showed the absence of a significant relationship in the coordinate condition (r = 0.24, P = 0.08), as well as in the attribute condition (r = –0.03, P = 0.85). Also, in the control group, no significant correlations were found between response times and semantic priming effects in both coordinate (r = 0.32, P = 0.17) and attribute conditions (r = 0.18, P = 0.45).
Correlations between semantic priming effects and dementia severity index
In the Alzheimer's disease group, a significant correlation was observed between priming effects in coordinate condition and the MMSE score and Mattis score (respectively, r = –0.42, P < 0.0001; r = –0.32, P = 0.021), the more severely affected patients showing the largest priming effects. No significant correlations were found between priming effects in attribute condition and MMSE or DRS scores (respectively, r = –0.21, P = 0.13; r = –0.18, P = 0.21).
Semantic knowledge task
Performances and correlations between semantic knowledge scores and dementia severity index
A two-way ANOVA with repeated measures: two groups (Alzheimer's disease and controls) x three tests (naming, categorical knowledge and attribute knowledge) showed a group effect [F(1,71) = 10.47, P = 0.002] and a test effect [F(2,71) = 8.62, P = 0.0003]. The analysis also showed a significant group x test interaction [F(2,71) = 5.08, P = 0.007].
Non-paired Student's t-tests indicated that the performances of the patients were inferior to those of the control subjects in naming [t(71) = 3.058, P = 0.003] and in the attribute knowledge test [t(71) = 3.248, P = 0.002], but not in the categorical knowledge test [t(71) = 1.301, P = 0.20].
The Alzheimer's disease group showed significant correlations between semantic knowledge scores and dementia severity index (MMSE r = 0.19, P < 0.0001; Mattis r = 0.36, P < 0.0001).
Correlations between semantic knowledge and semantic priming effects
In order to assess the influence of semantic deficits on the magnitude of the semantic priming effects in the Alzheimer's group, we looked for correlations between semantic priming effects in the two related conditions and the performances in the three tests of the semantic knowledge task. Among all the correlations, only one was significant—negative as expected—between semantic priming effects in coordinate condition and questions involving attribute knowledge (r = –0.29, P = 0.036). In other words, the more the specific attributes are degraded, the larger the priming effects in coordinate condition are.
Alzheimer's disease without semantic memory deficits versus patients with specific knowledge loss
In order to study the effect of these deficits on priming effects, we divided the group of patients into two subgroups on the basis of their results for the questions focused on specific knowledge in the semantic knowledge task. The first subgroup was composed of 27 patients with scores which did not exceed >1 SD of the mean of the control group (patients without semantic deficits). The second subgroup was composed of 26 patients with performances that exceeded >1 SD of the control group mean (patients with specific knowledge loss). We opted for this threshold of 1 SD below the mean of the control group, because the semantic knowledge task was not very sensitive, with a ceiling effect easily reached in controls. Furthermore, this threshold allowed to us to constitute two homogeneous subgroups with regard to the number of patients.
An ANOVA between the three groups of subjects (one control group and the two Alzheimer's disease groups) showed no significant differences in terms of age [F(2,70) =0.97, P = 0.39], education level [F(2,70) = 0.56, P = 0.57] or sex distribution [F(2,70) = 2.11, P = 0.13]. A post hoc analysis (PLSD Fisher's test) between the two groups of patients showed different performances for the MMSE (P =0.01), but not for the Mattis (P = 0.19).
A two-way ANOVA comparing response times: three groups (control, Alzheimer's disease without semantic deficits and Alzheimer's disease with semantic deficits) x three conditions (coordinate, attribute and unrelated) showed significant effects of group [F(2,70) = 12.047, P < 0.0001], and condition [F(2,70) = 112.294, P < 0.0001]. The interaction group x condition was also significant [F(4,70) =6.386, P < 0.0001]. Post hoc analysis (PLSD Fisher's test) showed that, in the three conditions, response times of the two groups of patients were similar (coordinate P = 0.86; attribute P = 0.73; unrelated P = 0.44) and significantly greater than those obtained by the controls (Table 1
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Semantic priming effects were submitted to a two-way ANOVA with repeated measures in three groups (control, Alzheimer's disease without semantic deficits and Alzheimer's disease with semantic deficits) x two conditions (coordinate and attribute). This analysis showed a group effect [F(2,70) = 3.1, P = 0.05], but no condition effect [F(1,70) = 0.994, P = 0.32]. On the other hand, the interaction group x condition was significant [F(2,70) =5.916, P = 0.004]: a one-factor ANOVA comparing semantic priming effects in the coordinate condition showed significant differences between the three groups of subjects [F(2,70) =7.906, P = 0.0008], post hoc analysis indicating in this experimental condition that the priming effects obtained by the patients with semantic deficits were significantly higher than those obtained by the patients without semantic deficits (P = 0.04) and than in the control group (P = 0.0002); patients without semantic deficits showed greater priming effects than in normals (P = 0.04). Concerning the semantic priming effects in the attribute condition, an ANOVA showed no significant difference between the three groups of subjects [F(2,70) = 0.884, P = 0.42] (Fig. 1). According to paired Student's t-tests, the control group appeared to show a lower amount of semantic priming effects in the coordinate condition than in the attribute condition [t(19) = –2.372, P = 0.18], whereas the semantic priming effects of the two groups of patients were greater in the coordinate condition than in the attribute condition {patients without semantic deficits [t(26) = 1.996, P = 0.05]; patients with semantic deficits [t(25) = 2.139, P = 0.04]}.
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The present findings show significant semantic priming effects for the Alzheimer's disease group and an experimental dissociation according to the condition: larger priming effects than the normals (hyperpriming) in the coordinate condition, and equivalent priming effects in the attribute condition. Furthermore, the subdivision of the Alzheimer's disease group according to the severity of the specific attribute deficits shows that the magnitude of the semantic priming effects in the coordinate condition varies according to the degree of specific attribute loss: the more the specific knowledge is impaired, the more the semantic priming effects are increased.
Hyperpriming and cognitive slowing
In the Alzheimer's disease group, the response times in the unrelated condition were longer than those of the control group. According to Nebes and colleagues, this slowing effect, which affects all cognitive operations in Alzheimer's disease, could be at the origin of the hyperpriming effect observed (Nebes et al., 1989); a patient with very long response times in the control condition (tiger–hammer) has more chance of showing a larger decrease in response times when the target is preceded by a related prime (tiger–lion), than in comparison with a subject who is already fast in the control condition. Comparing the results of a naming task from studies by Nebes and colleagues (Nebes et al., 1984, 1989), the authors observed that the priming effects were approximately the same for the controls in the two investigations (22 versus 19 ms, respectively), but were significantly larger for the Alzheimer's disease patients in the later study (118 versus 22 ms; Nebes et al., 1989). The overall response time for the controls in the two studies differed by only 23 ms, whereas the response time was >117 ms longer for the Alzheimer's disease patients in the 1989 study than for those in the 1984 study. One major difference between the two studies was in the frequency of the words which the subjects had to identify (134 per million in the 1989 study and 72 per million in the 1984 study). Stanovitch and West have shown that words that are less common, and thus take longer to identify, also show a larger priming effect (Stanovitch and West, 1983). The results of the present study contradict the explanation of Nebes and colleagues (1989) according to which hyperpriming would be an artefact of cognitive slowing: we used words with a lexical frequency similar to those of the 1984 study by Nebes and colleagues. Moreover, unlike the results of some studies, increased semantic priming effects obtained by the patients of our study are expressed as a percentage of the unassociated condition response time, which minimizes any effect of slowing on the size of the priming effect. Balota and co-workers first analysed priming effects in absolute values (milliseconds) and explained the Alzheimer's disease hyperpriming by the general slowing effect (Balota et al., 1999). But the authors conducted subsidiary analyses to determine if this pattern of data was based on general slowing. When the data were expressed as percentages, the hyperpriming effects were still reliable in the Alzheimer's disease group. Thus, the authors concluded that the overall increase in the priming effect cannot simply be attributed to general slowing effects. Moreover, we have shown that, in the Alzheimer's disease group and in the control group, there is no significant correlation between response times and magnitude of semantic priming effects, in the coordinate condition as well as in the attribute condition. Such results fit with a study by Chertkow and colleagues (Chertkow et al., 1992, cited in Chertkow et al., 1994) in which four groups of non-demented subjects (young normals, elderly normals, elderly Parkinson's patients and elderly depressed patients), with very heterogeneous response times, did not show a cognitive slowing effect on the magnitude of semantic priming. In addition, the degree of slowing seems to depend in part on the extent to which controlled processes are relevant to priming task performance (Shenaut and Ober, 1996). Thus, in the present investigation, the absence of an effect of slowing on the amount of priming may also be due to our protocol, which avoids the intervention of attentional processes.
Hyperpriming and attentional processes
The majority of authors who report hyperpriming in Alzheimer's disease partly explain this observation by the intervention of attentional strategies, such as expectancy and semantic matching mechanisms, which are, respectively, prelexical and postlexical processes (Nebes et al., 1989; Hartman, 1991; Chertkow et al., 1994; Silveri et al., 1996). A meta-analysis conducted by Ober and Shenaut suggests that hyperpriming mainly occurs in paradigms bringing into play these attentional processes (long SOAs, high proportions of related pairs and high proportions of non-words) (Ober and Shenaut, 1995). Thus, this hyperpriming effect would be the result of Alzheimer's disease strategic deficits (expectancy or postlexical semantic matching processes) in semantic priming tasks. Those attentional mechanisms involve divided attention and require the simultaneous processing of several types of information in working memory. Patients with Alzheimer's disease have considerable difficulty in dividing attention between concurrently running cognitive operations. Thus, when semantic priming tasks involve long SOAs and a high proportion of related pairs—which underlie an expectancy mechanism—the patients (like normal subjects) are attempting to divide their attention among generate, search and decision processes. However, these multiple cognitive operations `hamper' their impaired working memory, especially for the pairs in which words are unrelated and in which the potential targets will have to be inhibited. This will probably create a doubt for the patient about the decision asked for (`yes' the target is a word, or `yes' the target is related to the prime). This confusion is expressed by a magnified difference between the response times in unrelated targets and in targets related to the prime (due mainly to increased slowing for unrelated pairs) for Alzheimer's disease patients compared with controls.
In the present study, the adjustment of the protocol (SOA =250 ms, 20% of related words, response on the target only) did not allow the intervention of this expectancy mechanism. This incites us to conclude that the hyperpriming effect observed for our patients is not the result of the intervention of such a strategy. Moreover, for some authors (Jorm, 1986; Chenery et al., 1994), the patients are unconscious of the presence of related pairs, even for long SOAs, and thus do not bring into play an expectancy mechanism, but would rely more than normals on postlexical semantic matching processes (Neely and Keefe, 1989) to compensate for their deteriorating decision-making process (Neely, 1991), hence hyperpriming. If so, a number of studies in which a lexical decision task was used (Ober et al., 1991) should have also found increased priming effects, despite the use of shorter SOA (Chertkow et al., 1994), since postlexical semantic matching processes are not related, unlike the expectancy mechanism, to temporal variations between the prime and the target. In addition, postlexical semantic matching processes occur in binary decision tasks only (as in the lexical decision task), but Nebes and colleagues found an increased semantic priming effect on a pronunciation task in Alzheimer's disease patients (Nebes et al., 1989). The foregoing results suggest that hyperpriming observed in our patients cannot be due to this postlexical semantic matching mechanism, all the more so as our protocol involved as many target words as target non-words.
Hyperpriming and semantic degradation
An analysis of the group of subjects with Alzheimer's disease reveals two points. First, there is a negative correlation between semantic priming effects in the coordinate condition and specific knowledge scores. Secondly, when this group is separated into two groups (on the basis of their semantic deficits), the subgroup of patients with the more deteriorated specific attributes is the group which obtained the greater priming effects in the coordinate condition. These results agree with those of Chertkow and colleagues concerning words sharing a coordinate relation, where a hyperpriming effect is observed for the degraded items only (Chertkow et al., 1989). According to Chertkow et al. (1993), the semantic deterioration of some Alzheimer's disease patients would confuse the representations stored in memory, thus increasing the possibilities of interactions between those representations, hence hyperpriming. According to Eustache and Desgranges, hyperpriming could reflect the integrity of very automatic associations and all the more accessible since they belong to an impoverished semantic network (Eustache and Desgranges, 1995).
The present study elucidates and expounds these interpretations since our protocol does not involve attentional processes in the semantic priming effects, and the semantic related words are divided into two conditions according to the hierarchical organization of the semantic knowledge. Our results suggest that hyperpriming, encountered in the more impaired patients, reflects a deterioration of semantic memory and, more specifically, a storage deficit for specific attribute information: from the onset of the dementia, semantic representations deteriorate progressively, affecting the specific attributes first with preservation of general knowledge (Martin and Fedio, 1983). This makes the distinction between coordinate concepts more and more difficult since they share the same preserved superordinate category and their specific attributes, which allow them to be distinguished, are lost. In agreement with Martin's proposition, hyperpriming would be considered like a repetition priming (in which the prime and the target are the same) in which the intensity is greater than semantic priming's (Martin, 1992). In the coordinate condition, we obtained an evident hyperpriming in the Alzheimer's disease group with specific knowledge deterioration. The Alzheimer's disease group without semantic deficits (according to the semantic knowledge task) also obtained, but to a lesser degree, increased semantic priming effects when compared with controls. This result can be explained by the fact that semantic memory deficits are measured with a task in which the answers are very straightforward and for which a ceiling effect is quickly reached. This task would therefore not be sensitive enough to detect relatively minor semantic deficits. Besides, the presence of the hyperpriming phenomenon runs counter to one of the criteria of Warrington and Shallice, according to which the presence or absence of semantic priming can be used for distinguishing between disorders of storage and of access to semantic information (Warrington and Shallice, 1979). We agree with Moss and colleagues that one cannot infer from the presence of semantic priming that semantic representations are completely intact, and that any deficit on explicit tasks is located solely in controlled access to those representations (Moss et al., 1995a). Partial damage to representations also allows the occurrence of priming and hyperpriming despite the presence of a storage deficit for specific features. Indeed, in the attribute condition, we obtained no significant difference for the priming effects in the three groups of subjects.
Nevertheless, we suggest that the profile of the semantic priming effects in Alzheimer's disease evolves in a dynamic manner depending on the level of semantic memory deterioration. In order to complete and confirm this suggestion, the present study will be pursued longitudinally, since we expect that the hyperpriming observed is limited to a particular stage of semantic memory deterioration. The hypothesis of this longitudinal study implies at least three stages in the evolution of priming. First, when semantic memory is still entirely preserved, semantic priming effects should be similar in patients and their controls in both coordinate and attribute conditions. Secondly, when the semantic structure begins to deteriorate, at the level of specific attributes, a hyperpriming effect would occur in the coordinate condition—as we observed in the present investigation—and the semantic priming should begin to decrease in the attribute condition. We did not observe this result in our study, but we expect that, when the specific attribute loss progresses slightly further in the patients, the attribute priming effects will decrease as the semantic link between two words (tiger–stripe) becomes less and less strong. Thirdly, as semantic memory deteriorates even more, not only the specific attributes, but also the concepts themselves, are lost from memory. For this reason, in the attribute as well as the coordinate condition, the semantic priming effects should decrease because not even coordinate links between words will be remembered.
Taken together, these results, obtained by means of a very controlled methodology, allows one to conclude that the hyperpriming effect noted in some patients is not the result of a cognitive slowing which characterizes this population, or of their attention deficits. The link between the hyperpriming effect and the partial loss of semantic information from memory is strengthened by the fact that hyperpriming was found particularly for the group of patients with a storage deficit for attribute information, and only in the coordinate condition. Furthermore, our investigation supports current models of semantic memory and raises our knowledge of the structure and functioning of semantic memory in normal subjects.
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We wish to thank Professor J. Segui and Mrs J. Lambert for their methodological advice, Drs O. Letortu, S. Schaeffer and F. Viader for the recruitment of the patients and Mr K. Benali for the statistical analysis. We also wish to thank Dr A. Young for revising the English style. We also wish to acknowledge the three anonymous referees for their valuable comments.
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Received July 31, 2000. Revised January 5, 2001. Accepted March 19, 2001.
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