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Language functions in incipient cognitive decline in multiple sclerosis
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Journal of the Neurological Sciences 141 (1996) 79-86
Language functions in incipient cognitive decline in multiple sclerosis P%vi Kujala ay* , Raija Portin b, Juhani Ruutiainen a a Masku Neurological Rehabilitation Centre, P.O. Box 15, FIN-21251 Masku, Finland b Department of Neurology, University of Turku, Turku, Finland Received 18 October 1995; revised 22 March 1996; accepted 16 April 1996
Abstract Although the mechanismsof cognitive impairment in multiple sclerosis (MS) have been extensively studied, evaluation of language functions has been given little attention. In the present study, we evaluated whether impairment of language functions is associatedwith cognitive decline in MS. We studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. In language tasks, the patients with incipient cognitive decline not only demonstratedperformance slowness but also made more errors than the patients with preserved cognitive capacity and the healthy controls. The comprehensive naming error analysis revealed that the cognitively deteriorated patients produced error types not present in the other two study groups. Contrary to previous suggestions,the presentstudy indicates that impaired languageperformancesin MS are attributable to mild cognitive deterioration rather than to sensory or motor factors. Thus, assessmentof language functions should be included in neuropsychological evaluations of MS patients. Keywords: Language; Verbal performance; Cognitive deficit; Naming; Error analysis; Multiple sclerosis
1. Introduction Although the spectrum of cognitive deficits in multiple sclerosis (MS) has been reported to be widespread, it has been suggested that language functions remain relatively intact (Jambor, 1969; Beatty and Gange, 1977; Heaton et al., 1985; Franklin et al., 1988; Rao et al., 1991). Minor deficits in naming and reading have been explained as originating from non-cognitive factors, like problems in visual acuity and phonological apparatus (JennekensSchinkel et al., 1990). In some other studies, language deficits have been found (Beatty et al., 1988; Rao et al., 1989a; Pozzilli et al., 1991; Amato et al., 1995), but the origin of these deficits has remained controversial because of methodological problems. First, previous studies have mostly employed patient samples with unknown variability in the degree of general cognitive decline. This may be one reason for contradictory findings. Second, in previous studies, language tests which measure not only linguistic abilities but also many other aspects of cognition have been used. For example, the observed deficits in verbal fluency
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may have originated equally well from disruption of linguistic processes as from executive dysfunction or general information processing slowness. Indisputably, in research on cognitive impairment in MS, actual language functions have not been paid enough attention to. Thus, whereas we know that memory deficits and information processing slowness are common features of cognitive impairment in MS (cf. Rao, 1986; Litvan et al., 1988; Rao et al., 1989a; Rao et al., 1989b; Kujala et al., 1994, 199.51, we do not know whether also disruption of linguistic processes is associated with early cognitive deterioration in MS. In the present study, we evaluated the mechanisms of incipient cognitive decline in MS. In order to find out whether impairment of language functions is associated with cognitive decline in MS, we studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. By comparing the Preserved and the Mildly Deteriorated subgroups, we wanted to confirm that the possible language problems in the group with incipient cognitive decline are cognitive in origin. To evaluate whether the possible deficits in naming and reading reflect disruption of actual linguistic processes, we employed different kinds of naming and reading tests and measured both performance times and error rates. Furthermore, we tried to evaluate the
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nature of difficulties in one basic language function, i.e. naming, by means of a comprehensive picture-naming error analysis.
2. Methods 2.1. Subjects The study group consisted of 45 right handed patients with multiple sclerosis and 35 right handed healthy controls. The patients had clinically definite multiple sclerosis according to the criteria of Poser et al. (1983) and they were not in exacerbation at the time of the study. Patients with native tongue other than Finnish, drug or alcohol misuse, psychiatric history, dementia according to DSM (3rd ed.) criteria (American Psychiatric Association, 1980) moderate to severe dysarthria, hearing loss, or nervous system disorder other than multiple sclerosis were excluded from the study. The same patient group has also been described in previous studies of Kujala et al. (1994, 1995). After the neurological examination, all patients were assessed with a neuropsychological battery (Portin and Rinne, 1980; Revonsuo et al., 1993) to select patients suitable for either the ‘Cognitively Preserved’ or ‘Cognitively Mildly Deteriorated’ group (see below). The subjects were selected so that the study groups were as similar as possible with regard to non-cognitive variables: age (Controls 43.5 (9.1) Preserved 43.3 (8.7) Deteriorated 43.3 (7.2) years), sex (Controls 17 males/l8 females, Preserved 11/ 12, Deteriorated 11/ 1 l), education (Controls 11.3 (3.2) Preserved 11.6 (3.5), Deteriorated 11.0 (2.9) years), depression (Beck et al., 1961) (Controls 2.5 (3.0) Preserved 7.4 (6.1) Deteriorated 9.0 (6.2)) sight (Controls 1.6 (0.3) Preserved 1.4 (0.3) Deteriorated 1.4 (0.3)) and colour-sight (Ishihara, 1987) (Controls 23.1 (3.6) Preserved 20.3 (7.0) Deteriorated 19.0 (6.2)). The statistical analysis revealed that the patient groups did not differ from each other on these variables. The controls had, however, slightly better sight and colour-sight than the patients, but even in the patient groups the visual acuity was normal. The patient groups had more depression points in the Beck Depression Inventory than the controls. None of the patients, however, had severe depression. One of the deteriorated patients was taking psychoactive medication at the time of the evaluation. The patient groups did not differ from each other in medication usage. The patient groups were similar also with regard to the duration of multiple sclerosis (Preserved 8.7 (5.9) Deteriorated 8.7 (6.0) years), the physical disability as measured by the Kurtzke Expanded Disability Status Scale (EDSS) (Kurtzke, 1983) (Preserved 5.0 (1.8) Deteriorated 5.5 (1.3)) and the course of the disease (Preserved: 11 relapsing-remitting, 9 chronic-progressive, 3 secondary progressive; Deteriorated: 6 relapsing-remitting, 13 chronic-progressive, 3 secondary progressive). Four patients in the
Deteriorated group suffered from mild dysarthria exhibited as slowed speech production. All patients were informed about the study during the neurological status examination at the beginning of their rehabilitation course in the Masku Neurological Rehabilitation Centre. The controls included staff of the Rehabilitation Centre and other voluntary participants. All subjects gave their informed consent for participation in this study. 2.2. Neuropsychological patients into subgroups
battery used in the division of
All subjects were examined with screening tests (Portin and Rinne, 1980; Revonsuo et al., 1993) which were completed in a single session. On the basis of their performance on these tests the patients were allocated into two groups. The screening tests used were standardized Finnish versions of the following Wechsler Adult Intelligence Scale (WAIS, Wechsler, 1955) subtests: Similarities, Digit Span, Digit Symbol, Block Design. In addition, three memory tests were administered: the Benton Visual Retention Test (Benton, 1963) 30 Paired Word Associates (immediate recall), Immediate Recall of 20 Objects. The patients received ‘deterioration points’ if their performance on any of the tests was below - 1.5 standard deviations (SD) compared to norms based on the control group reported by Portin and Rinne (1980). On each screening test, O-3 deterioration points were given (see Kujala et al., 1994). The maximum deterioration score was thus 21 points. Patients with O-2 deterioration points were classified into the Cognitively Preserved group (23 patients) and patients with 3-9 deterioration points into the Cognitively Mildly Deteriorated group (22 patients). The controls had also O-2 deterioration points. In the Mildly Deteriorated group, the deterioration was selective in individual patients. They showed signs of incipient cognitive decline by performing mildly to moderately defectively on some subtests whereas normally on others (see Kujala et al., 1994). The mildly deteriorated patients as a group differed significantly from the other two groups in all the screening tests. The Preserved group performed more poorly than the controls on two of the tests, the WAIS Digit Symbol and Immediate Recall of 20 Objects. The individual patients in the Preserved group, however, performed normally on the screening battery. The mean (SD) of the deterioration points was 0.3 (0.6) for the controls, 0.6 (0.8) for the Preserved, and 5.2 (1.8) for the Deteriorated group. 2.3. Procedure Language tasks were carried out in Finnish in the same session as the screening tests. The session lasted 120-150 min. All the tests were administered in approximately the same order for every subject. On the untimed language tests, the subjects were given as much time as they needed
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to perform the test and only the number of correct answers and the error rates were recorded. In contrast, on the timed language tests, the subjects were instructed to perform as fast as they could because of the registration of performance times in addition to error rates. 2.4. Measures of naming 2.4.1. Timed colour naming The naming time of 100 coloured rectangles (red, yellow, blue, green) of the Stroop Colour-Word Test (Stroop, 1935) was used as a measure of relatively automatic colour naming performance. Furthermore, the number of flounderings (partly produced inappropriate word which is spontaneously corrected), corrected errors (spontaneously corrected inappropriate word), and errors (inappropriate word without correction) was recorded. None of these errors can be due to speech slowness. 2.4.2. Untimed picture naming The Finnish version of the Boston Naming Test (BNT; Laine et al., 1993) was used as a measure of picture naming. In this test, the subjects were asked to name line drawings of 60 items ranging in familiarity from bed to sarcophagus. By contrast to the standard administration of this test, no time limits were set. If the subject did not recognize the line drawing, a semantic cue (category name) was given. If the subject’s final response was not correct, a phonological cue (first syllable) was offered. According to the standard administration of this test, correct responses produced after semantic cuing were included in the total correct score. By means of an error analysis modified from the previous naming studies (Kohn and Goodglass, 1985; Hodges et al., 1991) the non-correct responses were classified into seven categories, which reflect deficits at different levels (perceptual, semantic, lexical, or phonological) of the cognitive naming process: 1. Visual errors: responses that are visually similar to the target but semantically and phonologically unrelated (e.g. ring-shaped bun - sausage). 2. Semantic-visual errors: responses from the same semantic category as the target and visually similar in that the error could be either perceptually or semantically based (e.g. dominoes - dice blocks). 3. Semantic-associative errors: semantically but not visually related responses (e.g. bed - chair). 4. Superordinates: responses denoting the general class or category to which the target belongs (e.g. rhinoceros animal). 5. Circumlocutory responses: multiword responses showing accurate identification of the target either by describing the function or action (e.g. rolling pin needed in baking for rolling) or by describing its attributes (e.g. sarcophagus - an egyptian statue) or by offering some knowledge about the structure of the target word (e.g. first syllable, word length: abacus -
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knows that you can calculate with it and knows the first syllable of the name). 6. Non-word responses: non-identifiable responses (nonwords). 7. Unrelated responses: responses in which no clear connection between the target and response could be found (e.g. cone - television). 2.5. Measures of reading 2.5. I. Timed reading In the word/non-word reading test, the subjects were instructed to read 40 words consisting of 20 real words and 20 non-words as fast as they could. The words and nonwords were in random order and were presented in the same order for every subject. In the colour reading test, the subjects were instructed to read 100 colour names (red, blue, green, yellow) printed in black as fast as they could. The third reading test was reading of a text paragraph. On all these tests, the reading time and the number of errors (flounderings, corrected errors and errors) were recorded. 2.5.2. Untimed reading The subjects were instructed to read aloud four paragraphs of the reading comprehension part of the standardized Finnish version of the Boston Diagnostic Aphasia Examination (BDAE) (Laine et al., 1993). The subjects were instructed to answer a question with four-choice answers after each paragraph. The subjects were told that there were no time limits. The number of errors (flounderings, corrected errors, and errors) was recorded during the first reading. The number of correct responses to the questions with four-choice answers served as a measure of reading comprehension. 2.6. Measures of writing 2.6.1. Writing The subjects were instructed to write five dictated words as well as their own name and the date. The number of correct words in the writing to dictation test was recorded. In the name and date writing test, two points for name and one for date were the maximum. In these tests poor writing style was not punished. 2.7. Data analyses Where all three groups were compared, ANOVAs and Duncan’s multiple comparisons test were used for parametric variables and the Kruskal-Wallis test and multiple comparisons for the Kruskal-Wallis test for non-parametric variables. Where the two patient groups alone were compared, t-tests and Chi squares were used. Correlation analyses were employed to measure the relationship between different variables. On the BNT, the proportion (%) of each error type was calculated for every subject by divid-
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ing the number of times an error of a particular type occurred by the total number of errors (excluding non-responses) made by that subject.
3. Results The MS group with incipient cognitive decline performed more poorly than the other two study groups on almost all language measures regardless of the presence of external time pressure. The patients with preserved cognitive capacities, in turn, performed almost as well as the controls. The error rates on all language tests were relatively small and, therefore, only the sum score of errors was analysed. The correlations between the main language variables and depression, sight, and colour-sight were non-significant for both MS groups. 3.1. Naming 3.1.1. Timed colour naming The Mildly Deteriorated group named the 100 coloured rectangles significantly more slowly than the other two groups (Table 1). The error rate in the Deteriorated group exceeded that of the control group. The Preserved group did not differ from the controls in these measures. 3.1.2. Untimed picture naming On the BNT, the Mildly Deteriorated group named significantly fewer pictures correctly than the other two groups (Table 1). The controls and the Preserved group did not differ from each other. Signs of perceptual deficits
were present only in some cases of unnamed objects. In these cases a semantic cue was offered. After a semantic cue, naming was successful in 30.0% of the unnamed items in the controls, in 42.9% in the Preserved group, and in 26.5% in the Deteriorated group. The phonological cue led to correct response in about half of the unnamed items (Controls 44.6%, Preserved 60.5%, Deteriorated 59.8%). Out of the non-correct answers, 66.0% were no responses in the controls, 65.9% in the Preserved group and 60.5% in the Deteriorated group. The analysis of the naming errors on the BNT revealed that the pattern of errors in the controls and in the preserved patients was quite similar (Table 2). By contrast, the mildly deteriorated patients differed slightly from the other subjects in their pattern of errors. As a sign of perceptual deficit in the naming process, the Deteriorated group tended to make a few visual errors which were absent in the other groups. Similarly, the deteriorated patients tended to produce more superordinate responses than the other subjects. This error type indicates that at least the right semantic field has been activated but probably the final semantic features cannot be accessed. Furthermore, the deteriorated patients exhibited some signs of phonological deficits by producing non-words, a phenomenon which was absent in the other subjects. The significantly higher number of unrelated responses in the deteriorated patients than in the controls may be associated with difficulty in recognizing the object or accessing the meaning properly. On the other hand, the deteriorated patients made significantly fewer semantic-visual errors than the other subjects. In the controls and in the Preserved group, semantic-visual errors were commonly clustered on
Table 1 The performance of the three study groups on different kinds of timed and untimed language tests
Naming Timed colour naming, time (s) Timed colour naming, error rate Untimed picture naming (BNT), correct Reading Timed reading Word/non-word reading, time (s) Word/non-word reading, error rate Reading of 100 colour names, time (s) Reading of 100 colour names, error rate Text reading, time (s) Text reading, error rate Untimed reading Reading comprehension, correct Untimed reading, error rate Writing Writing to dictation, correct Writing name and date, correct
Controls mean (SD)
Preserved mean (SD)
Mildly Deteriorated mean (SD)
p-value
62.9 (11.5) 1.5 (1.9) 56.0 (2.7)
71.3 (14.1) 2.0 (2.1) 56.5 (2.5)
105.4 (25.9) 3.5 (3.1) 51.4 (6.6)
p < 0.001 * p = 0.004 # p = 0.002 *
29.2 (10.5) 1.0 (1.3) 51.7 (9.2) 0.2 (0.4) 83.5 (19.7) 3.6 (3.2)
32.6 (12.7) 1.2 (1.6) 58.3 (11.0) 0.5 (1.1) 71.3 (14.1) 4.1 (4.3)
55.7 (17.7) 3.1 (2.4) 93.3 (25.7) 2.8 (5.0) 105.4 (25.9) 9.4 (7.7)
p
3.8 (0.5) 1.3 (1.5)
3.7 (0.5) 1.7 (1.7)
3.3 (1.2) 4.7 (3.6)
p = 0.072 p=o.O01*
4.9 (0.3) 2.9 (0.2)
5.0 (0.2) 2.9 (0.3)
4.4 (1.2) 2.9(0.3)
p = 0.038 p = 0.867
* The Mildly Deteriorated group differs significantly ( p < 0.05) from the other two study groups. # The Mildly Deteriorated group differs significantly ( p < 0.05) from the controls.
P. Kujala et al. /Journal Table 2 Distribution
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of errors on the untimed picture naming (the BNT) in the three study groups. Preserved mean (SD)
Mildly Deteriorated mean (SD)
p-value
mean (SD)
0.0 (0.0) 52.0 (27.6) 30.3 (24.4) 0.0 (0.0) 15.8 (27.3) 0.0 (0.0) 1.9 (7.9)
0.0 (0.0) 50.3 (45.3) 26.7 (37.0) 0.0 (0.0) 20.6 (29.7) 0.0 (0.0) 2.4 (8.9)
0.3 (1.3) 16.5 (16.7) 36.2 (34.7) 4.9 (12.2) 25.2 (34.7) 7.1 (24.4) 9.8 (13.7)
p = 0.390 p = 0.002 *
Controls Visual, % Semantic-visual, % Semantic-associative, % Superordinate, % Circumlocutions, % Non-words, % Unrelated, %
p = 0.611 p = 0.053 p = 0.568 p = 0.146 p=O.O18#
Only subjects with at least one error were included (Controls: n = 18, Preserved: n = 14, Mildy Deteriorated: n = 17). * The Mildly Deteriorated group differs significantly ( p < 0.05) from the other two study groups. # The Mildly Deteriorated group differs significantly ( p < 0.05) from the controls.
the rarely encountered line drawings of dominoes, sea horse and unicorn which were usually misnamed as dice blocks, dragon, and circus horse, respectively. The distribution of different error types on the BNT was highly variable from subject to subject. The preserved patients and the controls made mainly one or two types of errors, while most patients with impaired naming made many types of errors. One mildly deteriorated patient who succeeded in naming only 32 pictures correctly, made 18 errors of which 5.6% were visual, 44.4% semantic-visual, 38.8% semantic-associative, 5.6% circumlocutory errors, and 5.6% unrelated responses. 3.2. Reading 3.2.1. Timed reading
On all the timed reading tests, the Mildly Deteriorated group performed more slowly than the other two groups (Table 1). The analyses of error rates showed that the Deteriorated group made more errors than the other two groups on the word/non-word reading and on the text reading. On the reading of colour names the error rate of the Deteriorated group exceeded that of the controls. No differences were present between the controls and the preserved patients on these measures (Table 1). On the word/non-word reading test; all three groups made errors in non-word reading, the Deteriorated group, in addition, in word reading. 3.2.2. Untimed
reading
The mildly deteriorated patients made significantly more errors than the other two groups in the BDAE reading test. They also tended to perform more poorly than the other two groups on the reading comprehension (Table 1). 3.3. Writing 3.3. I. Writing
The Mildly Deteriorated group tended to perform more poorly than the other two groups on the writing to dictation test. Due to ceiling effects, the differences between the subgroups did not reach statistical significance (Table
1). The errors were letter omissions and substitutions. No statistically significant differences were observed on the relatively automatic writing of name and date. 3.4. Summary
In one of the four timed tests, the Mildly Deteriorated group produced significantly more flounderings than the controls (word/non-word reading: p = 0.021). In two of the four reading and naming tests, the deteriorated patients made more corrected errors than the controls (colour naming: p = 0.036, text reading: p = 0.009). Because of corrections, these two error types tend to add to the naming and reading time. In all four tests the Deteriorated group made more non-corrected errors than the other study groups (colour naming: p < 0.001, word/non-word reading: p < 0.001, colour reading: p = 0.004, text reading: p < 0.001). Consequently, the deteriorated patients mostly made noncorrected errors which did not add to the naming and reading time.
4. Discussion The present study demonstrates that many aspects of language functions are impaired even in incipient cognitive decline in MS. The mildly deteriorated patients exhibited performance slowness on the timed language tests. Interestingly, they also made more errors on both the timed and untimed language tests and produced naming error types which were absent in the other study groups. By contrast, the cognitively preserved MS patients performed as well as the healthy controls on language tasks. The difficulties of the deteriorated patients on language tests indisputably originate from cognitive factors, because the patient groups were matched with respect to non-cognitive factors. Whereas performance slowness on language tests may be associated with more general information processing slowness, the increased error rates, especially the rare types of errors, may reflect disruption of linguistic processes as an underlying mechanism of the observed deficits.
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The rationale of this study was to uncover the characteristics of cognitive decline in MS using patient groups with predetermined cognitive status. Previous studies on language impairment in MS have mostly employed patient samples with high interpatient variability with respect to cognitive as well as other disease-related variables. By using very heterogeneous study groups, the origin and nature of the observed deficits have remained unclear. Subgrouping according to cognitive status has been employed only in one previous study concerning verbal performance (Beatty et al., 1988). In their study, however, the subgrouping was based on the Mini-Mental State Examination (MMSE, Folstein et al., 1975) which has been reported to be insensitive in identifying cognitive decline in MS patients (Beatty and Goodkin, 1990; Swirsky-Sacchetti et al., 1992; Kujala et al., 1994; Kujala et al., 1995). On the other hand, the MMSE consists of many items which call for basic language skills, such as naming, repetition, comprehension, reading, and writing. Because of the insensitivity and the contents of the MMSE, it cannot be considered a sensible tool in patient selection when evaluating the role of language functions in early cognitive decline in MS. Therefore, we employed a more comprehensive screening battery which consists of measures of immediate memory, abstract reasoning, visuomotor, and visuoconstructive abilities, but not direct language measures (Wechsler, 1955; Portin and Rinne, 1980; Kujala et al., 1994; Kujala et al., 1995). Thus, the present study design comprised two cognitively homogeneous patient groups - one with preserved cognitive capacities and the other representing incipient stages of cognitive decline (see Kujala et al., 1994). The mildly deteriorated patients showed impairments in relatively automatic colour naming as well as in more complicated picture naming. They were slower and produced more errors than the other subjects also on all kinds of reading tests. On the other hand, on reading comprehension and on writing tests, they showed only a mild tendency towards deficits. The Preserved group, in turn, performed similarly to the controls on all language tasks. Whereas the patient groups were matched with respect to non-cognitive variables, the language difficulties in the deteriorated patients were clearly cognitive in origin. The present results on affected language functions in MS are in agreement with the findings of Achiron et al. (1992) who have reported linguistic problems in a couple of MS cases, and with Amato et al. (1995) who found signs of language impairments in their follow-up study. Our findings, however, contradict the observations of Jennekens-Schinkel et al. (1990) who have claimed that language deficits in MS are purely non-cognitive. Dysarthria, fine-motor deficits, depression, and problems with visual acuity, all typical of MS, may, indeed, interfere with language performance and should be taken into account in neuropsychological evaluations. Indeed, four of our deteriorated patients suffered from mild dysarthria, which may have caused some slow-
ness on verbal production. Dysarthria does not, however, explain the high error rates, the various types of naming errors or the slight difficulties in reading comprehension and writing. Consequently, MS-related language impairments are not only attributable to sensory or motor deficits but, instead, seem to represent one underlying characteristic of cognitive impairment. Previous studies on language impairment in MS have mostly employed language measures with external time pressure, such as tests of timed naming, reading, and verbal fluency (Beatty et al., 1988; Jennekens-Schinkel et al., 1990; Pozzilli et al., 1991; Amato et al., 1995). Deficits on these kinds of tests may be associated not only with disruption of linguistic processes but also with other cognitive impairments, such as slowed information processing which is a general feature of even mild cognitive decline in MS (Litvan et al., 1988; Rao et al., 1989b; Kujala et al., 1994; Kujala et al., 1995). To find out whether our MS patients fail in language tasks because of cognitive processing slowness (see Kujala et al., 1994) or because of actual language impairments, we also used untimed language tasks, measured error rates and analysed error types. On all the timed tests, the deteriorated patients exhibited performance slowness, which cannot be explained by the time the patients needed for error corrections because most of the errors remained uncorrected. Interestingly, they made more errors both on timed and untimed tests and produced rare error types in the picture-naming task. The performance slowness of the deteriorated patients on timed language tests could well be explained by a general cognitive slowness, but the higher error rates as well as slight difficulties in reading comprehension and writing indicate additional impairments of true language functions. Consequently, language deficits in MS patients may originate from several factors. The possibility of disruption of true linguistic processes in MS gained further support from the present findings of the picture-naming error analysis. In the untimed picture naming task (BNT), the error analysis revealed a different error profile in the Deteriorated group than in the other two groups. Unfortunately, even in this comprehensive test, the error corpus was rather limited because the deteriorated patients were only mildly affected. The deteriorated patients, however, made significantly more errors than the other subjects. According to aphasia studies, naming can be compromised by deficits in recognizing the object (perceptual level), in finding the semantic meaning of an object (semantic level), in finding the lexical form of the to-be-named object (lexical level), or in assembling the phonological segments of the to-be-produced word (phonological level) (Gainotti et al., 1981; Kohn and Goodglass, 1985; Ellis and Young, 1988). Our naming error analysis demonstrated that visual and superordinate errors and non-words were present only in the Deteriorated group and the number of unrelated names was significantly higher in the deteriorated patients than in the controls. The visual errors are indicative of
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pathology on the perceptual level, the superordinate errors on the semantic-lexical level, and the non-words on the phonological level. The unrelated names, in turn, may be a result of dysfunction at multiple levels of the naming process. Most commonly, however, naming seemed to fail because of difficulties in finding the right semantic features of the target (semantic-associative errors) or in finding the right lexical form of the to-be-named target (circumlocutory responses), which is in line with the findings of Beatty and Monson (1989) and Beatty et al. (1989). Thus, the present study suggests that anomia and the tip-of-the-tongue phenomenon, frequently reported by MS patients themselves, may be due to deficits at many stages of the word-finding process. Whereas comprehensive classification of naming errors has not been employed in previous studies, further studies assessing patients with more extensive anomia and using Magnetic Resonance Imaging techniques are needed to elucidate the mechanisms of naming failures in MS and their relationship to diffuse subcortical lesions. In conclusion, contrary to previous beliefs, language functions are vulnerable even in incipient cognitive decline in MS. While the present study reports findings about disrupted linguistic processes as a mechanism underlying the difficulties on the language tests, it calls for further studies on the nature of language impairments in MS. In a clinical sense, the present study indisputably indicates the importance of including assessment of various language functions in neuropsychological evaluations of MS patients. Acknowledgements We gratefully acknowledge the support given to this study by the Emil Aaltonen Foundation. We thank our patients for their time and interest in this study. We are grateful to Matti Laine PhD for his comments on the earlier versions of this manuscript. References Achiron, A., I. Ziv, R. Djaldetti, H. Goldberg, A. Kuritzky, and E. Melamed (1992) Aphasia in multiple sclerosis: Clinical and radiologic correlations. Neurology, 42: 2195-2197. Amato, M.P., G. Ponziani, G. Pracucci, L. Bracco, G. Siracusa, and L. Amaducci (1995) Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up. Arch. Neurol., 52: 168-172. American Psychiatric Association. (1980) Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., Washington (DC). Beatty, P.A. and J.J. Gange (1977) Neuropsychological aspects of multiple sclerosis. J. Nerv. Ment. Dis., 164: 42-50. Beatty, W.W. and D.E. Goodkin (1990) Screening for cognitive impairment in multiple sclerosis. An evaluation of the Mini-Mental State Examination. Arch. Neurol., 47: 297-301. Beatty, W.W., D.E. Goodkin, N. Monson, P.A. Beatty, and D. Hertsgaard (1988) Anterograde and retrograde amnesia in patients with chronic progressive multiple sclerosis. Arch. Neural., 45: 611-619.
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Beatty, W.W. and N. Monson (1989) Lexical processing in Parkinson’s disease and multiple sclerosis. J. Geriatr. Psychiatry Neurol., 2: 145-152. Beatty, W.W., N. Monson, and D.E. Goodkin (1989) Access to semantic memory in Parkinson’s disease and multiple sclerosis. J. Geriatr. Psychiatry Neurol., 2: 153-162. Beck, A.T., C.H. Ward, M. Mendelson, J. Mock, and J.K. Erbaugh (1961) An inventory for measuring depression. Arch. Gen. Psychiatry, 4: 561-571. Benton, A.L. (1963) The Revised Visual Retention Test, Psychological Carp, New York. Ellis, A.W. and A. Young (1988) Human Cognitive Neuropsychology, Lea, Hove. Folstein, M.F., S.E. Folstein and P.R. MC Hugh (1975) ‘Mini-Mental State’: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatric Res., 12: 189-198. Franklin, G.M., R.K. Heaton, L.M. Nelson, C.M. Filley, and C. Seibert (1988) Correlation of nemopsychological and MRI findings in chronic/progressive multiple sclerosis. Neurology, 38: 1826-1829. Gainotti, G., G. Miceli, C. Caltagirone, M.C. Silveri, and C. Masullo (1981) The relationship between type of naming error and semanticlexical discrimination in aphasic patients. Cortex, 17: 401-409. Heaton, R.K., L.M. Nelson, D.S. Thompson, J.S. Burks, and G.M. Franklin (1985) Neuropsychological findings in relapsing-remitting and chronic-progressive multiple sclerosis. J. Consult. Clin. Psychol., 53: 103-l 10. Hodges, J.R., D.P. Salmon, and N. Butters (1991) The nature of the naming deficits in Alzheimer’s and Huntington’s disease. Brain, 114: 1547-1558. Ishihara, S. (1987) The series of plates designed as a test for colour-blindness. 24 plates edition. Kanehara, Tokyo. Jambor, K.L. (1969) Cognitive functioning in multiple sclerosis. Br. J. Psychiatry, 115: 765-775. Jennekens-Schinkel, A., J.B.K. Lanser, E.A. van der Velde, and E.A.C.M. Sanders (1990) Performances of multiple sclerosis patients in tasks requiring language and visuoconstruction. Assessment of outpatients in quiescent disease stages. J. Neurol. Sci., 95: 89-103. Kohn, S.E. and H. Goodglass (1985) Picture-naming in aphasia. Brain Lang., 24: 266-283. Kujala, P., R. Portin, A. Revonsuo, and J. Ruutiainen (1994) Automatic and controlled information processing in multiple sclerosis. Brain, 117: 1115-1126. Kujala, P., R. Portin, A. Revonsuo, and J. Ruutiainen (1995) Attention related performance in two cognitively different subgroups of patients with multiple sclerosis. J. Neural. Neurosurg. Psychiatry, 59: 77-82. Kurtzke, J.F. (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology, 33: 14441452. Laine, M., H. Goodglass, J. Niemi, P. Koivuselka-Sallinen, J. Tuomainen, and R. Marttila (1993) Adaptation of the Boston Diagnostic Aphasia Examination and the Boston Naming Test into Finnish. Stand. J. Log. Phon., 18: 83-92. Litvan, I., J. Grafman, P. Vendrell, and J.M. Martinez (1988) Slowed information processing in multiple sclerosis. Arch. Neurol., 45: 281285. Portin, R. and U.K. Rinne (1980) Neuropsychological responses of parkinsonian patients to long-term levodopa treatment. In: Rinne, U.K., M. Klinger, and G. Stamm (Eds.) Parkinson’s disease-current progress, problems and management, Biomedical Press, Elsevier, pp. 271-304. Poser, C.M., D.W. Paty, L. Scheinberg, W.I. McDonald, F.A. Davis, G.C. Ebers, K.P. Johnson, W.A. Sibley, D.H. Silberberg and W.W. Tourtellotte (1983) New diagnostic criteria for multiple sclerosis: Guidelines for research protocols, Ann. Neurol., 13: 227-231. Pozzilli, C., S. Bastianello, A. Padovani, D. Passafiume, E. Millefiorini, L. Bozzao, and C. Fieschi (1991) Anterior corpus callosum atrophy and verbal fluency in multiple sclerosis. Cortex, 27: 441-445.
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Rao, SM. (1986) Neuropsychology of multiple sclerosis: a critical review. J. Clin. Exp. Neuropsychol., 8: 503-542. Rao, SM., G.J. Leo, and P. St. Aubin-Faubert (1989a) On the nature of memory disturbance in multiple sclerosis. J. Clin. Exp. Neuropsychol., 11: 699-712. Rao, SM., P. St. Aubin-Faubert, and G.J. Leo (1989b) Information processing speed in patients with multiple sclerosis. J. Clin. Exp. Neuropsychol., 11: 471-477. Rao, S.M., G.J. Leo, L. Bemardin, and F. Unverzagt (1991) Cognitive dysfunction in multiple sclerosis. 1. Frequency, patterns, and prediction. Neurology, 41: 685-691.
Revonsuo, A., R. Portin, L. Koivikko, J.0 Rinne, and U.K. Rinne (19931 Slowing of information processing in Parkinson’s disease. Brain Cogn., 21: 87-110. Stroop, J.R. (1935) Studies of interference in serial verbal reactions. J. Exp. Psychol., 18: 643-662. Swirsky-Sacchetti, T., H.L. Field, D.R. Mitchell, J. Seward, F.D. Lublin, R.L. Knobler, and C.F. Gonzalez (1992) The sensitivity of the mini-mental state examination in the white matter dementia of multiple sclerosis. J. Clin. Psychol., 48: 779-786. Wechsler, D. (1955) Manual for Wechsler Adult Intelligence Scale, Psychological Corp, New York.
OF THE
NEUROLOGICAL SCIENCES
ELSEVIER
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Language functions in incipient cognitive decline in multiple sclerosis P%vi Kujala ay* , Raija Portin b, Juhani Ruutiainen a a Masku Neurological Rehabilitation Centre, P.O. Box 15, FIN-21251 Masku, Finland b Department of Neurology, University of Turku, Turku, Finland Received 18 October 1995; revised 22 March 1996; accepted 16 April 1996
Abstract Although the mechanismsof cognitive impairment in multiple sclerosis (MS) have been extensively studied, evaluation of language functions has been given little attention. In the present study, we evaluated whether impairment of language functions is associatedwith cognitive decline in MS. We studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. In language tasks, the patients with incipient cognitive decline not only demonstratedperformance slowness but also made more errors than the patients with preserved cognitive capacity and the healthy controls. The comprehensive naming error analysis revealed that the cognitively deteriorated patients produced error types not present in the other two study groups. Contrary to previous suggestions,the presentstudy indicates that impaired languageperformancesin MS are attributable to mild cognitive deterioration rather than to sensory or motor factors. Thus, assessmentof language functions should be included in neuropsychological evaluations of MS patients. Keywords: Language; Verbal performance; Cognitive deficit; Naming; Error analysis; Multiple sclerosis
1. Introduction Although the spectrum of cognitive deficits in multiple sclerosis (MS) has been reported to be widespread, it has been suggested that language functions remain relatively intact (Jambor, 1969; Beatty and Gange, 1977; Heaton et al., 1985; Franklin et al., 1988; Rao et al., 1991). Minor deficits in naming and reading have been explained as originating from non-cognitive factors, like problems in visual acuity and phonological apparatus (JennekensSchinkel et al., 1990). In some other studies, language deficits have been found (Beatty et al., 1988; Rao et al., 1989a; Pozzilli et al., 1991; Amato et al., 1995), but the origin of these deficits has remained controversial because of methodological problems. First, previous studies have mostly employed patient samples with unknown variability in the degree of general cognitive decline. This may be one reason for contradictory findings. Second, in previous studies, language tests which measure not only linguistic abilities but also many other aspects of cognition have been used. For example, the observed deficits in verbal fluency
* Corresponding author. Tel: +358 (21) 4392 111. Fax: +358 (21) 4392 112.
may have originated equally well from disruption of linguistic processes as from executive dysfunction or general information processing slowness. Indisputably, in research on cognitive impairment in MS, actual language functions have not been paid enough attention to. Thus, whereas we know that memory deficits and information processing slowness are common features of cognitive impairment in MS (cf. Rao, 1986; Litvan et al., 1988; Rao et al., 1989a; Rao et al., 1989b; Kujala et al., 1994, 199.51, we do not know whether also disruption of linguistic processes is associated with early cognitive deterioration in MS. In the present study, we evaluated the mechanisms of incipient cognitive decline in MS. In order to find out whether impairment of language functions is associated with cognitive decline in MS, we studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. By comparing the Preserved and the Mildly Deteriorated subgroups, we wanted to confirm that the possible language problems in the group with incipient cognitive decline are cognitive in origin. To evaluate whether the possible deficits in naming and reading reflect disruption of actual linguistic processes, we employed different kinds of naming and reading tests and measured both performance times and error rates. Furthermore, we tried to evaluate the
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nature of difficulties in one basic language function, i.e. naming, by means of a comprehensive picture-naming error analysis.
2. Methods 2.1. Subjects The study group consisted of 45 right handed patients with multiple sclerosis and 35 right handed healthy controls. The patients had clinically definite multiple sclerosis according to the criteria of Poser et al. (1983) and they were not in exacerbation at the time of the study. Patients with native tongue other than Finnish, drug or alcohol misuse, psychiatric history, dementia according to DSM (3rd ed.) criteria (American Psychiatric Association, 1980) moderate to severe dysarthria, hearing loss, or nervous system disorder other than multiple sclerosis were excluded from the study. The same patient group has also been described in previous studies of Kujala et al. (1994, 1995). After the neurological examination, all patients were assessed with a neuropsychological battery (Portin and Rinne, 1980; Revonsuo et al., 1993) to select patients suitable for either the ‘Cognitively Preserved’ or ‘Cognitively Mildly Deteriorated’ group (see below). The subjects were selected so that the study groups were as similar as possible with regard to non-cognitive variables: age (Controls 43.5 (9.1) Preserved 43.3 (8.7) Deteriorated 43.3 (7.2) years), sex (Controls 17 males/l8 females, Preserved 11/ 12, Deteriorated 11/ 1 l), education (Controls 11.3 (3.2) Preserved 11.6 (3.5), Deteriorated 11.0 (2.9) years), depression (Beck et al., 1961) (Controls 2.5 (3.0) Preserved 7.4 (6.1) Deteriorated 9.0 (6.2)) sight (Controls 1.6 (0.3) Preserved 1.4 (0.3) Deteriorated 1.4 (0.3)) and colour-sight (Ishihara, 1987) (Controls 23.1 (3.6) Preserved 20.3 (7.0) Deteriorated 19.0 (6.2)). The statistical analysis revealed that the patient groups did not differ from each other on these variables. The controls had, however, slightly better sight and colour-sight than the patients, but even in the patient groups the visual acuity was normal. The patient groups had more depression points in the Beck Depression Inventory than the controls. None of the patients, however, had severe depression. One of the deteriorated patients was taking psychoactive medication at the time of the evaluation. The patient groups did not differ from each other in medication usage. The patient groups were similar also with regard to the duration of multiple sclerosis (Preserved 8.7 (5.9) Deteriorated 8.7 (6.0) years), the physical disability as measured by the Kurtzke Expanded Disability Status Scale (EDSS) (Kurtzke, 1983) (Preserved 5.0 (1.8) Deteriorated 5.5 (1.3)) and the course of the disease (Preserved: 11 relapsing-remitting, 9 chronic-progressive, 3 secondary progressive; Deteriorated: 6 relapsing-remitting, 13 chronic-progressive, 3 secondary progressive). Four patients in the
Deteriorated group suffered from mild dysarthria exhibited as slowed speech production. All patients were informed about the study during the neurological status examination at the beginning of their rehabilitation course in the Masku Neurological Rehabilitation Centre. The controls included staff of the Rehabilitation Centre and other voluntary participants. All subjects gave their informed consent for participation in this study. 2.2. Neuropsychological patients into subgroups
battery used in the division of
All subjects were examined with screening tests (Portin and Rinne, 1980; Revonsuo et al., 1993) which were completed in a single session. On the basis of their performance on these tests the patients were allocated into two groups. The screening tests used were standardized Finnish versions of the following Wechsler Adult Intelligence Scale (WAIS, Wechsler, 1955) subtests: Similarities, Digit Span, Digit Symbol, Block Design. In addition, three memory tests were administered: the Benton Visual Retention Test (Benton, 1963) 30 Paired Word Associates (immediate recall), Immediate Recall of 20 Objects. The patients received ‘deterioration points’ if their performance on any of the tests was below - 1.5 standard deviations (SD) compared to norms based on the control group reported by Portin and Rinne (1980). On each screening test, O-3 deterioration points were given (see Kujala et al., 1994). The maximum deterioration score was thus 21 points. Patients with O-2 deterioration points were classified into the Cognitively Preserved group (23 patients) and patients with 3-9 deterioration points into the Cognitively Mildly Deteriorated group (22 patients). The controls had also O-2 deterioration points. In the Mildly Deteriorated group, the deterioration was selective in individual patients. They showed signs of incipient cognitive decline by performing mildly to moderately defectively on some subtests whereas normally on others (see Kujala et al., 1994). The mildly deteriorated patients as a group differed significantly from the other two groups in all the screening tests. The Preserved group performed more poorly than the controls on two of the tests, the WAIS Digit Symbol and Immediate Recall of 20 Objects. The individual patients in the Preserved group, however, performed normally on the screening battery. The mean (SD) of the deterioration points was 0.3 (0.6) for the controls, 0.6 (0.8) for the Preserved, and 5.2 (1.8) for the Deteriorated group. 2.3. Procedure Language tasks were carried out in Finnish in the same session as the screening tests. The session lasted 120-150 min. All the tests were administered in approximately the same order for every subject. On the untimed language tests, the subjects were given as much time as they needed
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to perform the test and only the number of correct answers and the error rates were recorded. In contrast, on the timed language tests, the subjects were instructed to perform as fast as they could because of the registration of performance times in addition to error rates. 2.4. Measures of naming 2.4.1. Timed colour naming The naming time of 100 coloured rectangles (red, yellow, blue, green) of the Stroop Colour-Word Test (Stroop, 1935) was used as a measure of relatively automatic colour naming performance. Furthermore, the number of flounderings (partly produced inappropriate word which is spontaneously corrected), corrected errors (spontaneously corrected inappropriate word), and errors (inappropriate word without correction) was recorded. None of these errors can be due to speech slowness. 2.4.2. Untimed picture naming The Finnish version of the Boston Naming Test (BNT; Laine et al., 1993) was used as a measure of picture naming. In this test, the subjects were asked to name line drawings of 60 items ranging in familiarity from bed to sarcophagus. By contrast to the standard administration of this test, no time limits were set. If the subject did not recognize the line drawing, a semantic cue (category name) was given. If the subject’s final response was not correct, a phonological cue (first syllable) was offered. According to the standard administration of this test, correct responses produced after semantic cuing were included in the total correct score. By means of an error analysis modified from the previous naming studies (Kohn and Goodglass, 1985; Hodges et al., 1991) the non-correct responses were classified into seven categories, which reflect deficits at different levels (perceptual, semantic, lexical, or phonological) of the cognitive naming process: 1. Visual errors: responses that are visually similar to the target but semantically and phonologically unrelated (e.g. ring-shaped bun - sausage). 2. Semantic-visual errors: responses from the same semantic category as the target and visually similar in that the error could be either perceptually or semantically based (e.g. dominoes - dice blocks). 3. Semantic-associative errors: semantically but not visually related responses (e.g. bed - chair). 4. Superordinates: responses denoting the general class or category to which the target belongs (e.g. rhinoceros animal). 5. Circumlocutory responses: multiword responses showing accurate identification of the target either by describing the function or action (e.g. rolling pin needed in baking for rolling) or by describing its attributes (e.g. sarcophagus - an egyptian statue) or by offering some knowledge about the structure of the target word (e.g. first syllable, word length: abacus -
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knows that you can calculate with it and knows the first syllable of the name). 6. Non-word responses: non-identifiable responses (nonwords). 7. Unrelated responses: responses in which no clear connection between the target and response could be found (e.g. cone - television). 2.5. Measures of reading 2.5. I. Timed reading In the word/non-word reading test, the subjects were instructed to read 40 words consisting of 20 real words and 20 non-words as fast as they could. The words and nonwords were in random order and were presented in the same order for every subject. In the colour reading test, the subjects were instructed to read 100 colour names (red, blue, green, yellow) printed in black as fast as they could. The third reading test was reading of a text paragraph. On all these tests, the reading time and the number of errors (flounderings, corrected errors and errors) were recorded. 2.5.2. Untimed reading The subjects were instructed to read aloud four paragraphs of the reading comprehension part of the standardized Finnish version of the Boston Diagnostic Aphasia Examination (BDAE) (Laine et al., 1993). The subjects were instructed to answer a question with four-choice answers after each paragraph. The subjects were told that there were no time limits. The number of errors (flounderings, corrected errors, and errors) was recorded during the first reading. The number of correct responses to the questions with four-choice answers served as a measure of reading comprehension. 2.6. Measures of writing 2.6.1. Writing The subjects were instructed to write five dictated words as well as their own name and the date. The number of correct words in the writing to dictation test was recorded. In the name and date writing test, two points for name and one for date were the maximum. In these tests poor writing style was not punished. 2.7. Data analyses Where all three groups were compared, ANOVAs and Duncan’s multiple comparisons test were used for parametric variables and the Kruskal-Wallis test and multiple comparisons for the Kruskal-Wallis test for non-parametric variables. Where the two patient groups alone were compared, t-tests and Chi squares were used. Correlation analyses were employed to measure the relationship between different variables. On the BNT, the proportion (%) of each error type was calculated for every subject by divid-
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ing the number of times an error of a particular type occurred by the total number of errors (excluding non-responses) made by that subject.
3. Results The MS group with incipient cognitive decline performed more poorly than the other two study groups on almost all language measures regardless of the presence of external time pressure. The patients with preserved cognitive capacities, in turn, performed almost as well as the controls. The error rates on all language tests were relatively small and, therefore, only the sum score of errors was analysed. The correlations between the main language variables and depression, sight, and colour-sight were non-significant for both MS groups. 3.1. Naming 3.1.1. Timed colour naming The Mildly Deteriorated group named the 100 coloured rectangles significantly more slowly than the other two groups (Table 1). The error rate in the Deteriorated group exceeded that of the control group. The Preserved group did not differ from the controls in these measures. 3.1.2. Untimed picture naming On the BNT, the Mildly Deteriorated group named significantly fewer pictures correctly than the other two groups (Table 1). The controls and the Preserved group did not differ from each other. Signs of perceptual deficits
were present only in some cases of unnamed objects. In these cases a semantic cue was offered. After a semantic cue, naming was successful in 30.0% of the unnamed items in the controls, in 42.9% in the Preserved group, and in 26.5% in the Deteriorated group. The phonological cue led to correct response in about half of the unnamed items (Controls 44.6%, Preserved 60.5%, Deteriorated 59.8%). Out of the non-correct answers, 66.0% were no responses in the controls, 65.9% in the Preserved group and 60.5% in the Deteriorated group. The analysis of the naming errors on the BNT revealed that the pattern of errors in the controls and in the preserved patients was quite similar (Table 2). By contrast, the mildly deteriorated patients differed slightly from the other subjects in their pattern of errors. As a sign of perceptual deficit in the naming process, the Deteriorated group tended to make a few visual errors which were absent in the other groups. Similarly, the deteriorated patients tended to produce more superordinate responses than the other subjects. This error type indicates that at least the right semantic field has been activated but probably the final semantic features cannot be accessed. Furthermore, the deteriorated patients exhibited some signs of phonological deficits by producing non-words, a phenomenon which was absent in the other subjects. The significantly higher number of unrelated responses in the deteriorated patients than in the controls may be associated with difficulty in recognizing the object or accessing the meaning properly. On the other hand, the deteriorated patients made significantly fewer semantic-visual errors than the other subjects. In the controls and in the Preserved group, semantic-visual errors were commonly clustered on
Table 1 The performance of the three study groups on different kinds of timed and untimed language tests
Naming Timed colour naming, time (s) Timed colour naming, error rate Untimed picture naming (BNT), correct Reading Timed reading Word/non-word reading, time (s) Word/non-word reading, error rate Reading of 100 colour names, time (s) Reading of 100 colour names, error rate Text reading, time (s) Text reading, error rate Untimed reading Reading comprehension, correct Untimed reading, error rate Writing Writing to dictation, correct Writing name and date, correct
Controls mean (SD)
Preserved mean (SD)
Mildly Deteriorated mean (SD)
p-value
62.9 (11.5) 1.5 (1.9) 56.0 (2.7)
71.3 (14.1) 2.0 (2.1) 56.5 (2.5)
105.4 (25.9) 3.5 (3.1) 51.4 (6.6)
p < 0.001 * p = 0.004 # p = 0.002 *
29.2 (10.5) 1.0 (1.3) 51.7 (9.2) 0.2 (0.4) 83.5 (19.7) 3.6 (3.2)
32.6 (12.7) 1.2 (1.6) 58.3 (11.0) 0.5 (1.1) 71.3 (14.1) 4.1 (4.3)
55.7 (17.7) 3.1 (2.4) 93.3 (25.7) 2.8 (5.0) 105.4 (25.9) 9.4 (7.7)
p
3.8 (0.5) 1.3 (1.5)
3.7 (0.5) 1.7 (1.7)
3.3 (1.2) 4.7 (3.6)
p = 0.072 p=o.O01*
4.9 (0.3) 2.9 (0.2)
5.0 (0.2) 2.9 (0.3)
4.4 (1.2) 2.9(0.3)
p = 0.038 p = 0.867
* The Mildly Deteriorated group differs significantly ( p < 0.05) from the other two study groups. # The Mildly Deteriorated group differs significantly ( p < 0.05) from the controls.
P. Kujala et al. /Journal Table 2 Distribution
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of errors on the untimed picture naming (the BNT) in the three study groups. Preserved mean (SD)
Mildly Deteriorated mean (SD)
p-value
mean (SD)
0.0 (0.0) 52.0 (27.6) 30.3 (24.4) 0.0 (0.0) 15.8 (27.3) 0.0 (0.0) 1.9 (7.9)
0.0 (0.0) 50.3 (45.3) 26.7 (37.0) 0.0 (0.0) 20.6 (29.7) 0.0 (0.0) 2.4 (8.9)
0.3 (1.3) 16.5 (16.7) 36.2 (34.7) 4.9 (12.2) 25.2 (34.7) 7.1 (24.4) 9.8 (13.7)
p = 0.390 p = 0.002 *
Controls Visual, % Semantic-visual, % Semantic-associative, % Superordinate, % Circumlocutions, % Non-words, % Unrelated, %
p = 0.611 p = 0.053 p = 0.568 p = 0.146 p=O.O18#
Only subjects with at least one error were included (Controls: n = 18, Preserved: n = 14, Mildy Deteriorated: n = 17). * The Mildly Deteriorated group differs significantly ( p < 0.05) from the other two study groups. # The Mildly Deteriorated group differs significantly ( p < 0.05) from the controls.
the rarely encountered line drawings of dominoes, sea horse and unicorn which were usually misnamed as dice blocks, dragon, and circus horse, respectively. The distribution of different error types on the BNT was highly variable from subject to subject. The preserved patients and the controls made mainly one or two types of errors, while most patients with impaired naming made many types of errors. One mildly deteriorated patient who succeeded in naming only 32 pictures correctly, made 18 errors of which 5.6% were visual, 44.4% semantic-visual, 38.8% semantic-associative, 5.6% circumlocutory errors, and 5.6% unrelated responses. 3.2. Reading 3.2.1. Timed reading
On all the timed reading tests, the Mildly Deteriorated group performed more slowly than the other two groups (Table 1). The analyses of error rates showed that the Deteriorated group made more errors than the other two groups on the word/non-word reading and on the text reading. On the reading of colour names the error rate of the Deteriorated group exceeded that of the controls. No differences were present between the controls and the preserved patients on these measures (Table 1). On the word/non-word reading test; all three groups made errors in non-word reading, the Deteriorated group, in addition, in word reading. 3.2.2. Untimed
reading
The mildly deteriorated patients made significantly more errors than the other two groups in the BDAE reading test. They also tended to perform more poorly than the other two groups on the reading comprehension (Table 1). 3.3. Writing 3.3. I. Writing
The Mildly Deteriorated group tended to perform more poorly than the other two groups on the writing to dictation test. Due to ceiling effects, the differences between the subgroups did not reach statistical significance (Table
1). The errors were letter omissions and substitutions. No statistically significant differences were observed on the relatively automatic writing of name and date. 3.4. Summary
In one of the four timed tests, the Mildly Deteriorated group produced significantly more flounderings than the controls (word/non-word reading: p = 0.021). In two of the four reading and naming tests, the deteriorated patients made more corrected errors than the controls (colour naming: p = 0.036, text reading: p = 0.009). Because of corrections, these two error types tend to add to the naming and reading time. In all four tests the Deteriorated group made more non-corrected errors than the other study groups (colour naming: p < 0.001, word/non-word reading: p < 0.001, colour reading: p = 0.004, text reading: p < 0.001). Consequently, the deteriorated patients mostly made noncorrected errors which did not add to the naming and reading time.
4. Discussion The present study demonstrates that many aspects of language functions are impaired even in incipient cognitive decline in MS. The mildly deteriorated patients exhibited performance slowness on the timed language tests. Interestingly, they also made more errors on both the timed and untimed language tests and produced naming error types which were absent in the other study groups. By contrast, the cognitively preserved MS patients performed as well as the healthy controls on language tasks. The difficulties of the deteriorated patients on language tests indisputably originate from cognitive factors, because the patient groups were matched with respect to non-cognitive factors. Whereas performance slowness on language tests may be associated with more general information processing slowness, the increased error rates, especially the rare types of errors, may reflect disruption of linguistic processes as an underlying mechanism of the observed deficits.
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The rationale of this study was to uncover the characteristics of cognitive decline in MS using patient groups with predetermined cognitive status. Previous studies on language impairment in MS have mostly employed patient samples with high interpatient variability with respect to cognitive as well as other disease-related variables. By using very heterogeneous study groups, the origin and nature of the observed deficits have remained unclear. Subgrouping according to cognitive status has been employed only in one previous study concerning verbal performance (Beatty et al., 1988). In their study, however, the subgrouping was based on the Mini-Mental State Examination (MMSE, Folstein et al., 1975) which has been reported to be insensitive in identifying cognitive decline in MS patients (Beatty and Goodkin, 1990; Swirsky-Sacchetti et al., 1992; Kujala et al., 1994; Kujala et al., 1995). On the other hand, the MMSE consists of many items which call for basic language skills, such as naming, repetition, comprehension, reading, and writing. Because of the insensitivity and the contents of the MMSE, it cannot be considered a sensible tool in patient selection when evaluating the role of language functions in early cognitive decline in MS. Therefore, we employed a more comprehensive screening battery which consists of measures of immediate memory, abstract reasoning, visuomotor, and visuoconstructive abilities, but not direct language measures (Wechsler, 1955; Portin and Rinne, 1980; Kujala et al., 1994; Kujala et al., 1995). Thus, the present study design comprised two cognitively homogeneous patient groups - one with preserved cognitive capacities and the other representing incipient stages of cognitive decline (see Kujala et al., 1994). The mildly deteriorated patients showed impairments in relatively automatic colour naming as well as in more complicated picture naming. They were slower and produced more errors than the other subjects also on all kinds of reading tests. On the other hand, on reading comprehension and on writing tests, they showed only a mild tendency towards deficits. The Preserved group, in turn, performed similarly to the controls on all language tasks. Whereas the patient groups were matched with respect to non-cognitive variables, the language difficulties in the deteriorated patients were clearly cognitive in origin. The present results on affected language functions in MS are in agreement with the findings of Achiron et al. (1992) who have reported linguistic problems in a couple of MS cases, and with Amato et al. (1995) who found signs of language impairments in their follow-up study. Our findings, however, contradict the observations of Jennekens-Schinkel et al. (1990) who have claimed that language deficits in MS are purely non-cognitive. Dysarthria, fine-motor deficits, depression, and problems with visual acuity, all typical of MS, may, indeed, interfere with language performance and should be taken into account in neuropsychological evaluations. Indeed, four of our deteriorated patients suffered from mild dysarthria, which may have caused some slow-
ness on verbal production. Dysarthria does not, however, explain the high error rates, the various types of naming errors or the slight difficulties in reading comprehension and writing. Consequently, MS-related language impairments are not only attributable to sensory or motor deficits but, instead, seem to represent one underlying characteristic of cognitive impairment. Previous studies on language impairment in MS have mostly employed language measures with external time pressure, such as tests of timed naming, reading, and verbal fluency (Beatty et al., 1988; Jennekens-Schinkel et al., 1990; Pozzilli et al., 1991; Amato et al., 1995). Deficits on these kinds of tests may be associated not only with disruption of linguistic processes but also with other cognitive impairments, such as slowed information processing which is a general feature of even mild cognitive decline in MS (Litvan et al., 1988; Rao et al., 1989b; Kujala et al., 1994; Kujala et al., 1995). To find out whether our MS patients fail in language tasks because of cognitive processing slowness (see Kujala et al., 1994) or because of actual language impairments, we also used untimed language tasks, measured error rates and analysed error types. On all the timed tests, the deteriorated patients exhibited performance slowness, which cannot be explained by the time the patients needed for error corrections because most of the errors remained uncorrected. Interestingly, they made more errors both on timed and untimed tests and produced rare error types in the picture-naming task. The performance slowness of the deteriorated patients on timed language tests could well be explained by a general cognitive slowness, but the higher error rates as well as slight difficulties in reading comprehension and writing indicate additional impairments of true language functions. Consequently, language deficits in MS patients may originate from several factors. The possibility of disruption of true linguistic processes in MS gained further support from the present findings of the picture-naming error analysis. In the untimed picture naming task (BNT), the error analysis revealed a different error profile in the Deteriorated group than in the other two groups. Unfortunately, even in this comprehensive test, the error corpus was rather limited because the deteriorated patients were only mildly affected. The deteriorated patients, however, made significantly more errors than the other subjects. According to aphasia studies, naming can be compromised by deficits in recognizing the object (perceptual level), in finding the semantic meaning of an object (semantic level), in finding the lexical form of the to-be-named object (lexical level), or in assembling the phonological segments of the to-be-produced word (phonological level) (Gainotti et al., 1981; Kohn and Goodglass, 1985; Ellis and Young, 1988). Our naming error analysis demonstrated that visual and superordinate errors and non-words were present only in the Deteriorated group and the number of unrelated names was significantly higher in the deteriorated patients than in the controls. The visual errors are indicative of
P. Kujala et al./ Journal of the Neurological
pathology on the perceptual level, the superordinate errors on the semantic-lexical level, and the non-words on the phonological level. The unrelated names, in turn, may be a result of dysfunction at multiple levels of the naming process. Most commonly, however, naming seemed to fail because of difficulties in finding the right semantic features of the target (semantic-associative errors) or in finding the right lexical form of the to-be-named target (circumlocutory responses), which is in line with the findings of Beatty and Monson (1989) and Beatty et al. (1989). Thus, the present study suggests that anomia and the tip-of-the-tongue phenomenon, frequently reported by MS patients themselves, may be due to deficits at many stages of the word-finding process. Whereas comprehensive classification of naming errors has not been employed in previous studies, further studies assessing patients with more extensive anomia and using Magnetic Resonance Imaging techniques are needed to elucidate the mechanisms of naming failures in MS and their relationship to diffuse subcortical lesions. In conclusion, contrary to previous beliefs, language functions are vulnerable even in incipient cognitive decline in MS. While the present study reports findings about disrupted linguistic processes as a mechanism underlying the difficulties on the language tests, it calls for further studies on the nature of language impairments in MS. In a clinical sense, the present study indisputably indicates the importance of including assessment of various language functions in neuropsychological evaluations of MS patients. Acknowledgements We gratefully acknowledge the support given to this study by the Emil Aaltonen Foundation. We thank our patients for their time and interest in this study. We are grateful to Matti Laine PhD for his comments on the earlier versions of this manuscript. References Achiron, A., I. Ziv, R. Djaldetti, H. Goldberg, A. Kuritzky, and E. Melamed (1992) Aphasia in multiple sclerosis: Clinical and radiologic correlations. Neurology, 42: 2195-2197. Amato, M.P., G. Ponziani, G. Pracucci, L. Bracco, G. Siracusa, and L. Amaducci (1995) Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up. Arch. Neurol., 52: 168-172. American Psychiatric Association. (1980) Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., Washington (DC). Beatty, P.A. and J.J. Gange (1977) Neuropsychological aspects of multiple sclerosis. J. Nerv. Ment. Dis., 164: 42-50. Beatty, W.W. and D.E. Goodkin (1990) Screening for cognitive impairment in multiple sclerosis. An evaluation of the Mini-Mental State Examination. Arch. Neurol., 47: 297-301. Beatty, W.W., D.E. Goodkin, N. Monson, P.A. Beatty, and D. Hertsgaard (1988) Anterograde and retrograde amnesia in patients with chronic progressive multiple sclerosis. Arch. Neural., 45: 611-619.
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