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Use of the Mini-Mental State Exam in Middle-Aged and Older Outpatients With Schizophrenia
Use of the Mini-Mental State Exam in Middle-Aged and Older Outpatients With Schizophrenia Cognitive Impairment and Its Associations David J. Moore, Ph.D. Barton W. Palmer, Ph.D. Dilip V. Jeste, M.D.
Objective: The authors examined cognitive impairment with a commonly used cognitive screening tool (the Mini-Mental State Exam [MMSE]) and its relationship to psychopathology, functional status, and other clinically relevant participant characteristics in 161 middle-aged and older outpatients with schizophrenia and 86 normalcomparison participants (NCs). Methods: Participants completed the MMSE and standardized rating scales of psychopathology and motor symptoms. Other aspects of daily functioning were also evaluated. Results: Patients had worse mean MMSE scores than NCs; 23% of the patients, but no NCs, had MMSE totals ⱕ24 (a commonly used cutoff score to define impairment). Examination of the individual cognitive domains assessed by the MMSE showed that schizophrenia patients had the greatest impairment on tasks of word recall and attention. Among the patients, impaired MMSE performance was associated with lower education, living in a structured setting, being unmarried, and more severe negative symptoms. Conclusion: The MMSE was useful in detecting functionally relevant cognitive deficits among middle-aged and older schizophrenia patients who scored in the impaired range; however, those patients in the unimpaired range may still have subtle cognitive deficits that were not detected with the MMSE. (Am J Geriatr Psychiatry 2004; 12:412–419)
C
ognitive impairment has a central role in the functional disability associated with schizophrenia,1 but formal neuropsychological evaluations are generally not a routine part of clinical care for schizophrenia patients. This absence of comprehensive neu-
ropsychological evaluation may reflect the amount of time required to administer a comprehensive test battery and the need for a highly trained neuropsychologist to administer (or supervise) and interpret test results. A pragmatic compromise might be to use
Received April 12, 2004; revised April 30, 2004; accepted May 4, 2004. From the University of California, San Diego (UCSD), Department of Psychiatry (DJM,BWP,DVJ), the VA San Diego Healthcare System (DVJ), and the UCSD Stein Institute for Research on Aging (DVJ). Address correspondence to Barton W. Palmer, Ph.D., Department of Psychiatry, University of California, San Diego VA San Diego Healthcare System, 116A1, 3350 La Jolla Village Drive, San Diego, CA 92161. e-mail: [email protected] 䉷 2004 American Association for Geriatric Psychiatry
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Moore et al. brief screening instruments to identify patients whose cognitive deficits are severe enough to cause impairments in everyday functioning. Among these individuals, more detailed neuropsychological testing could then be conducted to better identify specific areas of cognitive decline that may have prognostic or therapeutic implications. The Mini-Mental State Exam (MMSE)2 is probably the most widely used screening instrument to detect neurocognitive impairment and chart its course. The MMSE is a 30-item quantitative measure of cognitive status that is easy to administer and score, is generally well tolerated even by very impaired patients, and takes 5 to 10 minutes to administer and score. The MMSE has 11 tasks, representing cognitive domains of 1) orientation to time; 2) orientation to place; 3) registration; 4) attention; 5) word recall; 6) object naming; 7) sentence repetition; 8) three-stage command; 9) word reading; 10) writing; and 11) copying. A potential advantage of using the MMSE with schizophrenia patients is that it permits characterization of low-functioning patients. Neuropsychological research on schizophrenia that uses large neuropsychological test batteries may be biased by exclusion of individuals who are unable to tolerate extensive testing. Several different cutoff scores on the MMSE have been proposed for indicating significant cognitive impairment: MMSE ⱕ20,3 MMSE ⱕ23,4,5 and MMSE ⱕ24.6 Normative data exist for healthy adults on the MMSE;7 however, most individuals still use raw scores to assess deficits. In the present study, participants were classified as cognitively impaired if their MMSE score was ⱕ24. This cutoff score has been shown to have the best combination of sensitivity and specificity for the detection of cognitive impairment.6 The specific domains within the MMSE have been closely examined in the study of Alzheimer disease (AD). Data suggest that impairment in serial-seven subtractions, delayed word recall, and orientation to date may be useful in identifying early-stage AD; deficits on orientation to time and place are seen in middle-stage AD; and sentence repetition, object naming, and following commands become impaired in latestage AD.8 There is also evidence from the AD literature that groups of four individual MMSE items may be as effective as the complete MMSE in differentiating NC participants from mild AD (day, date, recall of apple, recall of penny) and mild AD from
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moderate AD (month, city, spelling world backward, and county).9 To our knowledge, there have been no published large studies examining the pattern of domains assessed on the MMSE among middle-aged and older outpatients with schizophrenia, nor studies examining the domains of impairment at various levels of MMSE performance. Given that some researchers suggest a cognitive decline in older schizophrenia patients,10 whereas others contend that impairment in this group is relatively stable,11 we felt that the current study was important to conduct in this population. Previous studies of the MMSE in schizophrenia suggest a wide range of scores, and there is some evidence that MMSE scores predict functional impairment.10,12–15 For example, Bowie et al.12 showed that severe cognitive impairment (MMSE ⱕ10) was related to worse social functioning and negative symptoms in a group of chronically institutionalized older schizophrenia patients. A study of middle-aged and elderly schizophrenia outpatients from our own research center showed that MMSE scores were related to a measure of functional capacity (Direct Assessment of Functional Status).14 The goal of the current study was to 1) determine whether middle-aged and elderly schizophrenia patients have worse performance than normal-comparison participants (NCs) on the MMSE total and domain scores; 2) examine the pattern of MMSE errors among patients with schizophrenia; and 3) determine whether impaired performance on the MMSE total score and MMSE cutoff score (MMSE ⱕ24) correspond to meaningful differences in terms of level of structured living situation, social functioning, and psychopathology in the patients. We hypothesized that schizophrenia patients would have worse MMSE scores than age-matched NCs. On the basis of the large neuropsychological literature on schizophrenia,16,17 we also hypothesized that the most common MMSE errors would occur on items relating to attention and episodic-memory word recall. Finally, we postulated that patients with impaired MMSE scores (MMSE total ⱕ24) would be more likely than those with unimpaired MMSE scores to be in structured living situations (living in a board-and-care facility rather than an apartment or private residence), have fewer social contacts, and have more severe negative symptoms.
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MMSE and Schizophrenia METHODS Participants The present report analyzed archival MMSE data from 161 middle-aged and older outpatients with schizophrenia and 86 NCs, all of whom were participants in our Research Center on the Study of LateLife Psychosis at the University of California, San Diego (UCSD). Participants were age 40 or older, and the patients had a DSM-III-R18 or DSM-IV19 diagnosis of schizophrenia. Some of these participants have contributed MMSE data to previous reports from our Center.14,15 The present study includes an expanded sample and examines both a commonly used impairment criterion (MMSE total ⱕ24 defining impairment) and the pattern of errors among MMSE domains. Individuals in both groups were excluded for the presence of major clinically observable medical or neurological illnesses (e.g., head injury with a loss of consciousness ⬎30 minutes, stroke, Alzheimer disease). All of the individuals with schizophrenia were clinically stable outpatients at the time of their study participation. After identifying our patient sample, we selected demographically comparable NCs from our larger database. We placed primary emphasis on obtaining comparable age distributions in the two groups; however, where possible, NCs were also selected with similar levels of education, ethnicity, and gender (prioritized in that order). Although this article uses secondary data collected from previous Center protocols, all participants provided written informed consent for enrollment into the studies from which the present data were obtained. That study was reviewed and approved by our local Institutional Review Board (IRB). Cognitive Assessment All participants completed the MMSE,2 following standard administration and scoring procedures. If the score yielded from the “world” backward task was higher than that from the serial-sevens task, then the former was substituted for the latter in the total score and attention subcomponent. Participants were categorized as cognitively impaired if their MMSE score was ⱕ24.6 We also analyzed individual domains of MMSE items, including
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1. Orientation to time (season, date, day, month, year) 2. Orientation to place (floor, building, state, city, and country) 3. Registration (ball, flag, tree) 4. Attention (“serial-seven” subtractions or spelling “world” backwards [whichever was higher]) 5. Word recall (recalling ball, flag, tree) 6. Object naming (pencil, watch) 7. Sentence repetition (no ifs, ands, or buts) 8. Three-stage command (three-stage command) 9. Word reading (“Close your eyes”) 10. Writing (sentence) 11. Copying (copying pentagons)
Additional Measures We also examined data on participants’ marital status, history of alcohol abuse and/or dependence, schizophrenia subtype, age at onset of schizophrenia, duration of illness, and current daily dosages of neuroleptic medications. Neuroleptic dosages were converted to milligram chlorpromazine-equivalents (CPZE20). For the schizophrenia group, data were used from selected items in the Strauss Carpenter Prognostic Scale21 to evaluate recency of previous psychiatric hospitalizations, living situation (dichotomized to “unstructured”—in the community alone or with family member or friends, or “structured”— board-and-care), and frequency of social contacts (dichotomized to “once per week” or “less than once per week” based on the relative few individuals who reported gradations of social contacts). For a sizable subset of patients (sample sizes provided in the Results section), we also had information on the severity of psychopathology as measured with the Brief Psychiatric Rating Scale (BPRS22), the Positive and Negative Syndrome Scale (PANSS23), and/or the 17-item version of the Hamilton Rating Scale for Depression (Ham-D24). Severity of dyskinesia was evaluated with the Abnormal Involuntary Movement Scale (AIMS25). Statistical analyses. Demographic comparisons of patients versus NCs were conducted with t-tests for continuous variables and chi-square analyses for categorical variables. Stepwise linear regression was used to determine whether psychiatric diagnosis was a significant predictor of MMSE total score after con-
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Moore et al. trolling for education, gender, and ethnicity. Because there was significant skew among the MMSE scores for both the patients and NCs (which was not overcome by log, square root, or inverse functions), we used Mann-Whitney U tests to compare the MMSE performance among NCs versus schizophrenia patients. To examine the pattern of errors among the patients, we calculated the percentage of schizophrenia patients receiving less than a perfect score in a particular domain at cumulative levels of MMSE total score. Spearman’s correlations were calculated to evaluate the association between MMSE totals and the functional and psychiatric outcome variables in the patient group. Independent-sample t-tests or Pearson chi-square tests were used to evaluate differences on various functional and psychiatric variables for schizophrenia patients with normal versus impaired MMSE scores (MMSE ⱕ24). Because both age at onset of schizophrenia and total score on the AIMS were positively skewed, a log-transformation was applied to the age-at-onset variable, whereas the AIMS variable required a 1/XⳭC transformation before analysis. Statistical significance was defined as p ⱕ0.05 (two-tailed, where applicable).
RESULTS Schizophrenia patients were similar to the NCs in age, but had less education and were more likely to be white and male (Table 1). The difference in terms of education was expected and was within 1 education year. Patients were less likely to be married, and more likely to be living in a structured setting and TABLE 1.
have a history of alcohol abuse or dependence. Schizophrenia patients also had significantly lower mean MMSE totals than NCs (Table 1). This difference remained significant even after covarying for the effects of education, gender, and ethnicity (F[4, 241]⳱ 13.5; p ⬍0.001). In terms of specific MMSE domains, patients had worse performance on orientation, attention, word recall, three-stage command, writing, and construction; there were no significant differences in registration, object-naming, sentence repetition, and wordreading (Table 2). As shown in Table 3, regardless of the MMSE total score, very few patients missed items in the domains of registration, object naming, and word reading. Conversely, errors in word recall were common, even among the patients who only missed 1 of the 30 MMSE items (Table 3). When examining the domains with the greatest level of impairment at lower total MMSE scores, word recall and attention were the most likely impaired domains. Scores on the orientation to time and place, sentence repetition, writing, and copying items were slightly worse at lower levels of total MMSE score. As hypothesized, patients had the greatest difficulty with word-recall and attention regardless of the overall level of performance. Within the patient sample, Spearman correlations revealed a positive association of MMSE total with education (N⳱161; r⳱0.28; p ⬍0.001), and negative associations between MMSE total and severity of negative symptoms (PANSS Negative Symptom Subscale, N⳱98; r ⳱ –0.41; p ⬍0.001), and dyskinesia (AIMS Total: N⳱81; r ⳱ –0.18; p⳱0.04). Associations with other demographic, clinical, and functional vari-
Demographics of normal-comparison participants (NCS) and schizophrenia groups
Age, years Education, years Ethnicity: % non-white (N) Gender: % female (N) % Currently married (N) % With alcohol abuse or dependence (N) % Paranoid (N) Age at onset of schizophrenia, years Duration of illness, years Daily neuroleptic dose (mg CPZE) % in structured living facilities (N)
NCS (Nⴔ86)
Schizophrenia Patients (Nⴔ161)
t[df] or Pearson v2 [df] (N)
p
55.8 (9.2) 13.3 (2.3) 52.3% (45) 69.8% (60) 48.8% (42) 4.7% (4) N/A N/A N/A N/A 0% (0)
56.0 (8.7) 12.5 (2.5) 26.1% (42) 34.2% (55) 11.9% (19) 16.1% (26) 52% (84) 29.4 (12.5) 27.2 (12.7) 270 (865.5) 38.6% (62)
0.2 [245] ⳮ2.5 [245] 16.9[1] (N⳱247) 28.6[1] (N⳱247) 40.6[1] (N⳱245) 6.9[1] (N⳱247) N/A N/A N/A N/A 38.5[1] (N⳱207)
0.84 0.02 ⬍0.001 ⬍0.001 ⬍0.001 0.008 N/A N/A N/A N/A ⬍0.001
Note: Data are mean (standard deviation), unless otherwise indicated; N/A: not applicable; CPZE: chlorpromazine-equivalent (median is reported). Education variable was not normally distributed.
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MMSE and Schizophrenia ables were not significant. The majority of patients (80%) were taking at least one antipsychotic medication at the time of testing, and 28% (38/127) were on an atypical antipsychotic as their primary antipsychotic medication. There was no significant difference on the MMSE total score between those who were taking antipsychotic medications and those who were not (t[1,153]⳱1.3; p⳱0.19), nor was there a significant correlation between antipsychotic dose and performance on the MMSE (r ⳱ –0.12; p⳱0.13). Alcohol abuse or dependence was not associated with poorer MMSE total scores in the patient group (t[1,159] ⳱ –0.32; p⳱0.75). Using the pre-established cutoff score (MMSE total ⱕ24 defined as impaired), 37 (23%) of the patients, but none of the NCs had an impaired-range MMSE score (N⳱247; v2[1]⳱23.2; p ⬍0.001). Relative to those with an unimpaired MMSE total score, the cognitively impaired patients had less education, were less likely to be married, were more likely to be living in a structured setting, and had more severe negative symptoms (Table 4). Only one patient had an MMSE score ⱕ10.
DISCUSSION Consistent with our first hypothesis, schizophrenia patients had worse MMSE total scores than NCs. Within the schizophrenia group, the most frequently impaired cognitive domains were Word Recall and Attention, confirming our second hypothesis. Our final hypothesis was partially supported. Among the TABLE 2.
patients, impaired MMSE scores were associated with less education, a greater likelihood of being in a structured living situation, decreased likelihood of being currently married, and having worse negative symptoms; however, no association was observed between impaired MMSE scores and the frequency of social contacts. Whereas 23% of our sample had MMSE scores below 24, severe cognitive impairment (MMSE ⱕ1026) was very rare; only one patient in our sample had an MMSE score in that range. Among chronically institutionalized schizophrenia samples, there has been one report showing that 17% of patients had MMSE total scores of 10 or less12 and another indicating that the average MMSE score for inpatients was approximately 10.5.13 This points to considerable differences in cognitive functioning that may be observed in institutionalized versus community-dwelling schizophrenia patients. AD patients with mild-to-moderate impairment show difficulty in the areas of word recall, attention, and orientation8,9 that are similar to the impairment patterns seen among the middle-aged and older schizophrenia outpatients in our sample. However, late-stage AD patients have deficits in sentence repetition, object naming, and following commands,8 whereas none of the schizophrenia patients showed object naming difficulties, and impairments in sentence repetition and following commands were, respectively, the fifth and eighth most likely impaired domains among the most severely impaired individuals in our study (those with MMSE totals between 8 and 24). Further research with a larger sample of
MMSE total and domain scores for normal-comparison participants (NCS) and schizophrenia patients
Orientation to Time Orientation to Place Registration Attention Word Recall Object-Naming Sentence Repetition 3-Stage Command Word-Reading Writing Copying MMSE Total
Maximum Score
NCS (Nⴔ86)
Schizophrenia Patients (Nⴔ161)
Mann-Whitney U or z-Score
p
5 5 3 5 3 2 1 3 1 1 1 30
4.97 (0.18) 4.99 (0.11) 3.0 (0) 4.74 (0.57) 2.47 (0.84) 2.0 (0) 0.86 (0.35) 2.98 (0.15) 1.0 (0) 1.0 (0) 0.92 (0.28) 28.92 (1.25)
4.67 (0.78) 4.71 (0.80) 2.98 (0.24) 3.88 (1.63) 2.02 (1.08) 2.0 (0) 0.80 (0.40) 2.85 (0.44) 0.98 (0.16) 0.89 (0.31) 0.76 (0.43) 26.55 (3.72)
ⳮ3.8 ⳮ3.8 ⳮ0.7 ⳮ4.2 ⳮ3.1 0 ⳮ1.2 ⳮ2.7 ⳮ1.5 ⳮ3.1 ⳮ3.0 ⳮ5.7
⬍0.001 ⬍0.001 0.47 ⬍0.001 0.002 1.0 0.25 0.008 0.14 0.002 0.003 ⬍0.001
Note: Data are mean (standard deviation), unless otherwise indicated; N/A: A t-test or chi-square could not be computed for this variable because the standard deviations for both groups was 0. MMSE: Mini-Mental State Exam (minimum score for all MMSE domains is 0).
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Note: MMSE: Mini-Mental State Exam. Orientation to Time: maximum score ⳱ 5; Orientation to Place: maximum score ⳱ 5; Registration: maximum score ⳱ 3; Attention: maximum score ⳱ 5; Word Recall: maximum score ⳱ 3; Object-Naming: maximum score ⳱ 2; Sentence Repetition: maximum score ⳱ 1; 3-Stage Command: maximum score ⳱ 3; Word-Reading: maximum score ⳱ 1; Writing: maximum score ⳱ 1; Copying: maximum score ⳱ 1.
0% 9% (4/45) 15% (9/61) 18% (14/80) 21% (18/87) 25% (24/97) 25% (27/106) 26% (29/110) 26% (29/113) 27% (32/117) 31% (38/124) 54% (20/37) 5% (1/21) 7% (3/45) 7% (4/61) 5% (4/80) 6% (5/87) 6% (6/97) 10% (11/106) 10% (11/110) 11% (13/113) 11% (13/117) 14% (17/124) 32% (12/37) 14% (3/21) 0% 9% (4/45) 0% 12% (7/61) 0% 11% (9/80) 0% 14% (12/87) 0% 14% (14/97) 0% 13% (14/106) 0% 14% (15/110) 0% 13% (15/113) 0% 15% (17/117) 0% 16% (20/124) 3% (4/124) 22% (8/37) 11% (4/37) 0% 13% (6/45) 16% (10/61) 19% (15/80) 18% (16/87) 21% (20/97) 20% (21/106) 22% (24/110) 21% (24/113) 22% (26/117) 26% (32/124) 43% (16/37) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 52% (11/21) 55% (25/45) 57% (35/61) 65% (52/80) 66% (57/87) 68% (66/97) 66% (71/106) 67% (74/110) 68% (77/113) 68% (80/117) 70% (87/124) 81% (30/37) 19% (4/21) 22% (10/45) 30% (18/61) 34% (27/80) 36% (31/87) 42% (41/97) 47% (50/106) 49% (54/110) 50% (57/113) 52% (61/117) 55% (68/124) 100% (37/37) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 1% (1/124) 3% (1/37) 0% 2% (1/45) 2% (1/61) 6% (5/80) 8% (7/87) 10% (10/97) 16% (17/106) 17% (19/110) 17% (43/113) 18% (21/117) 23% (28/124) 54% (20/37) 21 45 61 80 87 97 106 110 113 117 124 37 29 28–29 27–29 26–29 25–29 24–29 23–29 22–29 21–29 20–29 8–29 8–24
10% (2/21) 20% (9/45) 25% (15/61) 26% (21/80) 25% (22/87) 24% (23/97) 23% (24/106) 24% (26/110) 24% (27/113) 26% (30/117) 28% (35/124) 35% (13/37)
Writing Word Reading 3-Stage Command Sentence Repetition Object Naming Word Recall Attention Registration Orientation to Place Orientation to Time N MMSE Total Score
TABLE 3.
Percentage of schizophrenia patients at cumulative levels of MMSE total score (row) who received less than a perfect score in a particular domain
Copying
Moore et al.
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schizophrenia patients with severe cognitive impairment would be useful to help determine the degree to which such differences reflect overall level of cognitive impairment, versus disorder-specific cognitive patterns. Applying the commonly used MMSE cutoff score of ⱕ24 in this study, 23% of the patients were classified as impaired. Studies from our group and others using more comprehensive neuropsychological test batteries show that approximately 75% of schizophrenia patients have at least mild-to-moderate cognitive deficits.27,28 The above studies differ in their approach to detecting impairment (the current study uses a simple cutoff score, whereas previous studies required impairment in multiple cognitive domains); however, the data suggest that an MMSE cutoff score of ⱕ24 is insensitive to some of the less-severe cognitive deficits often present in patients with this disorder. Greater sensitivity could be achieved by using a higher cutoff score, although this would come at the cost of decreased specificity. Thus, the MMSE is likely to be most useful as a means of efficiently identifying patients with moderate-to-severe cognitive deficits, rather than for screening out those with mild cognitive impairment. Of interest, however, word recall was often impaired even among patients with normal-range MMSE total scores; the word recall task in the MMSE might itself be a useful procedure for cognitive screening. Because those with the most severe deficits are likely to have the greatest functional dependence, the full MMSE may still be useful in identifying those individuals. It must be acknowledged that the MMSE was not explicitly designed for comparison of individual cognitive domains (different domains have different numbers of items with unknown equivalence in sensitivity to their respective cognitive constructs). Nonetheless, it is of interest that the domains we found to be impaired (Word Recall and Attention) are among those most commonly reported to be affected in studies of schizophrenia patients that make use of comprehensive neuropsychological batteries.16,17 Another limitation of the MMSE for use in schizophrenia patients is that it does not explicitly measure executive skills, which are frequently impaired even in schizophrenia patients with preserved intellect29 and may be particularly sensitive to cognitive problems in older schizophrenia patients.30 It is possible, however, that executive functioning skills may influ-
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MMSE and Schizophrenia ence performance on word recall and attention.31,32 Future studies are needed to develop brief measures that are sensitive and specific to the mild cognitive deficits typical in schizophrenia. In conclusion, middle-aged and older schizophrenia outpatients display worse performance on the MMSE than NCs. Schizophrenia patients had the most frequent difficulties in recall and attention. Also, MMSE scores were related to severity of negative symptoms and psychosocial functioning (education, structured living situation, and marital status). Thus, despite its known limitations, given the ease of administering and scoring the MMSE, wider use of the MMSE as part of clinical care may be warranted. PaTABLE 4.
tients scoring in the unimpaired range may still have undetected cognitive deficits, but those categorized as impaired are likely to have functionally-relevant cognitive deficits that might suggest a need for further neuropsychological evaluation. We thank the patients who participated in this study. We also thank Shah Golshan, Ph.D., and Gosia Kubiak, M.Sc., for their statistical consultation. Charles F. Reynolds III, M.D., served as the action editor for this manuscript. This work was supported, in part, by National Institute of Mental Health grants MH19934-10, MH5910105, and MH66248-02, and by the Department of Veterans Affairs.
MMSE impairment levels for schizophrenia patients (MMSE impairment cutoff score: ⱕ24)
Age, years Education, years Ethnicity: % non-white (N) Gender: % female (N) % Currently married (N) % with alcohol abuse or dependence (N) Age at onset of schizophrenia, years a Duration of illness, years % in structured living facilities (N) % with a hospitalization within last year (N) % with social contacts ⬎ once/week (N) BPRS (1–18) PANSS Positive score PANSS Negative score PANSS general psychopathology Ham-D (1–17) Total AIMS a
MMSE ⬎24 (Nⴔ124)
MMSE ⱕ24 (Nⴔ37)
t[df] or Pearson v2[df] (N)
p
55.5 (8.5) 13.0 (2.1) 23.4% (29) 31.5% (39) 15.4% (19) 15.3% (19) 29.8 (12.5) 26.2 (12.5) 31.0% (31) 35.3% (24) 50.0% (43) 33.4 (8.2) 15.9 (6.1) 15.4 (5.7) 30.1 (6.7) 9.4 (5.5) 2.7 (2.9)
57.7 (8.9) 10.9 (3.1) 35.1% (13) 43.2% (16) 0% (0) 18.9% (7) 28.0 (12.5) 30.6 (13.1) 60.6% (20) 40.0% (10) 41.7% (10) 33.2 (8.1) 15.3 (5.2) 19.2 (6.6) 31.1 (6.5) 9.4 (5.0) 3.5 (2.8)
ⳮ1.4 [159] 4.7 [158] 2.0 [1] (N⳱161) 1.8 [1] (N⳱161) 6.3 [1] (N⳱159) 0.3 [1] (N⳱161) 0.9 [144] ⳮ1.8 [146] 9.2 [1] (N⳱133) 0.2 [1] (N⳱93) 0.5 [1] (N⳱110) 0.1 [145] 0.4 [96] ⳮ2.8 [96] ⳮ0.7 [95] ⳮ0.03 [145] 1.8 [139]
0.18 ⬍0.001 0.15 0.18 0.01 0.60 0.35 0.07 0.001 0.68 0.47 0.92 0.66 0.006 0.50 0.98 0.07
Note: Data are mean (standard deviation), unless otherwise indicated; MMSE: Mini-Mental State Exam; AIMS: Abnormal Involuntary Movement Scale; BPRS: Brief Psychiatric Rating Scale; Ham-D: Hamilton Rating Scale for Depression; PANSS: Positive and Negative Syndrome Scale. Raw scores are reported for interpretation purposes. a Because both age at onset of schizophrenia and total score on the AIMS were positively skewed, a log-transformation was applied to the age-at-onset variable, whereas the AIMS variable required a 1/XⳭC transformation before analysis.
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in a total population: a comparison of two screening instruments. Age Ageing 1991; 20:396–403 6. Huen R, Papassotiropoulos A, Jennssen F: The validity of psychometric instruments for detection of dementia in the elderly general population. Int J Geriatr Psychiatry 1998; 13:368–380 7. Crum RM, Anthony JC, Bassett SS, et al: Population-based norms for the Mini-Mental State Exam by age and education level. JAMA 1993; 269:2386–2391 8. Ashford JW, Kolm P, Colliver JA, et al: Alzheimer patient evaluation and the Mini-Mental State: item characteristic curve analysis. J Gerontol 1989; 44:P139–P146 9. Fillenbaum GG, Wilkinson WE, Welsh KA, et al: Discrimination between stages of Alzheimer’s disease with subsets of Mini-Mental State Exam items: an analysis of Consortium to Establish a
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Moore et al. Registry for Alzheimer’s Disease data. Arch Neurol 1994; 51:916– 921 10. Harvey PD, Bertisch H, Friedman JI, et al: The course of functional decline in geriatric patients with schizophrenia: cognitive, functional, and clinical symptoms as determinants of change. Am J Geriatr Psychiatry 2003; 11:610–619 11. Heaton RK, Gladsjo JA, Palmer BW, et al: Stability and course of neuropsychological deficits in schizophrenia. Arch Gen Psychiatry 2001; 58:24–32 12. Bowie CR, Harvey PD, Moriarty PJ, et al: Cognitive assessment of geriatric schizophrenic patients with severe impairment. Arch Clin Neuropsychol 2002; 17:611–623 13. Harvey PD, Leff J, Trieman N, et al: Cognitive impairment in geriatric chronic schizophrenic patients: a cross-national study in New York and London. Int J Geriatr Psychiatry 1997; 12:1001–1007 14. Patterson TL, Klapow JC, Eastham J, et al: Correlates of functional status in older patients with schizophrenia. Psychiatry Res 1998; 80:41–52 15. Palmer BW, Bondi MW, Twamley EW, et al: Are late-onset schizophrenia spectrum disorders a neurodegenerative condition? annual rates of change on two dementia measures. J Neuropsychiatry Clin Neurosci 2003; 15:45–52 16. Heaton R, Paulsen J, McAdams LA, et al: Neuropsychological deficits in schizophrenia: relationship to age, chronicity, and dementia. Arch Gen Psychiatry 1994; 51:469–476 17. Heinrichs RW, Zakzanis KK: Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998; 12:426–445 18. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised. Washington, DC, American Psychiatric Press, 1987 19. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Press, 1994 20. Jeste DV, Wyatt RJ: Understanding and Treating Tardive Dyskinesia. New York, NY, Guilford Press, Inc., 1982
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21. Strauss JS, Carpenter WT: The prediction of outcome in schizophrenia, II: relationships between predictor and outcome variables. A Report from the World Health Organization International Pilot Study of Schizophrenia. Arch Gen Psychiatry 1974; 31:37–42 22. Overall JE, Gorham DR: The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10:799–812 23. Kay SR, Opler LA, Fiszbein A: Positive and Negative Syndrome Scale (PANSS) Rating Manual. San Rafael, CA, Social and Behavioral Sciences Documents, 1987 24. Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6:278–296 25. National Institute of Mental Health: Abnormal Involuntary Movement Scale (AIMS). Early Clinical Drug Evaluation Unit Intercom 1975; 4:3–6 26. National Institute for Clinical Excellence (NICE): Guidance on the use of donepezil, rivastigmine, and galantamine for the treatment of Alzheimer’s disease. London, UK, NICE, 2001 27. Palmer BW, Heaton RK, Paulsen JS, et al: Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 1997; 11:437–446 28. Kremen WS, Seidman LJ, Faraone SV, et al: The paradox of normal neuropsychological function in schizophrenia. J Abnorm Psychol 2000; 109:743–752 29. Weickert TW, Goldberg TE, Gold JM, et al: Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. Arch Gen Psychiatry 2000; 57:907–913 30. Fucetola R, Seidman LJ, Kremen WS, et al: Age and neuropsychologic function in schizophrenia: a decline in executive abilities beyond that observed in healthy volunteers. Biol Psychiatry 2000; 48:137–146 31. Paulsen JS, Salmon DP, Monsch AU, et al: Discrimination of cortical from subcortical dementias on the basis of memory and problem-solving tests. J Clin Psychol 1995; 51:48–58 32. Holthausen EA, Wiersma D, Sitskoom MM, et al: Long-term memory deficits in schizophrenia: primary or secondary dysfunction? Neuropsychology 2003; 17:539–547
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Objective: The authors examined cognitive impairment with a commonly used cognitive screening tool (the Mini-Mental State Exam [MMSE]) and its relationship to psychopathology, functional status, and other clinically relevant participant characteristics in 161 middle-aged and older outpatients with schizophrenia and 86 normalcomparison participants (NCs). Methods: Participants completed the MMSE and standardized rating scales of psychopathology and motor symptoms. Other aspects of daily functioning were also evaluated. Results: Patients had worse mean MMSE scores than NCs; 23% of the patients, but no NCs, had MMSE totals ⱕ24 (a commonly used cutoff score to define impairment). Examination of the individual cognitive domains assessed by the MMSE showed that schizophrenia patients had the greatest impairment on tasks of word recall and attention. Among the patients, impaired MMSE performance was associated with lower education, living in a structured setting, being unmarried, and more severe negative symptoms. Conclusion: The MMSE was useful in detecting functionally relevant cognitive deficits among middle-aged and older schizophrenia patients who scored in the impaired range; however, those patients in the unimpaired range may still have subtle cognitive deficits that were not detected with the MMSE. (Am J Geriatr Psychiatry 2004; 12:412–419)
C
ognitive impairment has a central role in the functional disability associated with schizophrenia,1 but formal neuropsychological evaluations are generally not a routine part of clinical care for schizophrenia patients. This absence of comprehensive neu-
ropsychological evaluation may reflect the amount of time required to administer a comprehensive test battery and the need for a highly trained neuropsychologist to administer (or supervise) and interpret test results. A pragmatic compromise might be to use
Received April 12, 2004; revised April 30, 2004; accepted May 4, 2004. From the University of California, San Diego (UCSD), Department of Psychiatry (DJM,BWP,DVJ), the VA San Diego Healthcare System (DVJ), and the UCSD Stein Institute for Research on Aging (DVJ). Address correspondence to Barton W. Palmer, Ph.D., Department of Psychiatry, University of California, San Diego VA San Diego Healthcare System, 116A1, 3350 La Jolla Village Drive, San Diego, CA 92161. e-mail: [email protected] 䉷 2004 American Association for Geriatric Psychiatry
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Moore et al. brief screening instruments to identify patients whose cognitive deficits are severe enough to cause impairments in everyday functioning. Among these individuals, more detailed neuropsychological testing could then be conducted to better identify specific areas of cognitive decline that may have prognostic or therapeutic implications. The Mini-Mental State Exam (MMSE)2 is probably the most widely used screening instrument to detect neurocognitive impairment and chart its course. The MMSE is a 30-item quantitative measure of cognitive status that is easy to administer and score, is generally well tolerated even by very impaired patients, and takes 5 to 10 minutes to administer and score. The MMSE has 11 tasks, representing cognitive domains of 1) orientation to time; 2) orientation to place; 3) registration; 4) attention; 5) word recall; 6) object naming; 7) sentence repetition; 8) three-stage command; 9) word reading; 10) writing; and 11) copying. A potential advantage of using the MMSE with schizophrenia patients is that it permits characterization of low-functioning patients. Neuropsychological research on schizophrenia that uses large neuropsychological test batteries may be biased by exclusion of individuals who are unable to tolerate extensive testing. Several different cutoff scores on the MMSE have been proposed for indicating significant cognitive impairment: MMSE ⱕ20,3 MMSE ⱕ23,4,5 and MMSE ⱕ24.6 Normative data exist for healthy adults on the MMSE;7 however, most individuals still use raw scores to assess deficits. In the present study, participants were classified as cognitively impaired if their MMSE score was ⱕ24. This cutoff score has been shown to have the best combination of sensitivity and specificity for the detection of cognitive impairment.6 The specific domains within the MMSE have been closely examined in the study of Alzheimer disease (AD). Data suggest that impairment in serial-seven subtractions, delayed word recall, and orientation to date may be useful in identifying early-stage AD; deficits on orientation to time and place are seen in middle-stage AD; and sentence repetition, object naming, and following commands become impaired in latestage AD.8 There is also evidence from the AD literature that groups of four individual MMSE items may be as effective as the complete MMSE in differentiating NC participants from mild AD (day, date, recall of apple, recall of penny) and mild AD from
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moderate AD (month, city, spelling world backward, and county).9 To our knowledge, there have been no published large studies examining the pattern of domains assessed on the MMSE among middle-aged and older outpatients with schizophrenia, nor studies examining the domains of impairment at various levels of MMSE performance. Given that some researchers suggest a cognitive decline in older schizophrenia patients,10 whereas others contend that impairment in this group is relatively stable,11 we felt that the current study was important to conduct in this population. Previous studies of the MMSE in schizophrenia suggest a wide range of scores, and there is some evidence that MMSE scores predict functional impairment.10,12–15 For example, Bowie et al.12 showed that severe cognitive impairment (MMSE ⱕ10) was related to worse social functioning and negative symptoms in a group of chronically institutionalized older schizophrenia patients. A study of middle-aged and elderly schizophrenia outpatients from our own research center showed that MMSE scores were related to a measure of functional capacity (Direct Assessment of Functional Status).14 The goal of the current study was to 1) determine whether middle-aged and elderly schizophrenia patients have worse performance than normal-comparison participants (NCs) on the MMSE total and domain scores; 2) examine the pattern of MMSE errors among patients with schizophrenia; and 3) determine whether impaired performance on the MMSE total score and MMSE cutoff score (MMSE ⱕ24) correspond to meaningful differences in terms of level of structured living situation, social functioning, and psychopathology in the patients. We hypothesized that schizophrenia patients would have worse MMSE scores than age-matched NCs. On the basis of the large neuropsychological literature on schizophrenia,16,17 we also hypothesized that the most common MMSE errors would occur on items relating to attention and episodic-memory word recall. Finally, we postulated that patients with impaired MMSE scores (MMSE total ⱕ24) would be more likely than those with unimpaired MMSE scores to be in structured living situations (living in a board-and-care facility rather than an apartment or private residence), have fewer social contacts, and have more severe negative symptoms.
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MMSE and Schizophrenia METHODS Participants The present report analyzed archival MMSE data from 161 middle-aged and older outpatients with schizophrenia and 86 NCs, all of whom were participants in our Research Center on the Study of LateLife Psychosis at the University of California, San Diego (UCSD). Participants were age 40 or older, and the patients had a DSM-III-R18 or DSM-IV19 diagnosis of schizophrenia. Some of these participants have contributed MMSE data to previous reports from our Center.14,15 The present study includes an expanded sample and examines both a commonly used impairment criterion (MMSE total ⱕ24 defining impairment) and the pattern of errors among MMSE domains. Individuals in both groups were excluded for the presence of major clinically observable medical or neurological illnesses (e.g., head injury with a loss of consciousness ⬎30 minutes, stroke, Alzheimer disease). All of the individuals with schizophrenia were clinically stable outpatients at the time of their study participation. After identifying our patient sample, we selected demographically comparable NCs from our larger database. We placed primary emphasis on obtaining comparable age distributions in the two groups; however, where possible, NCs were also selected with similar levels of education, ethnicity, and gender (prioritized in that order). Although this article uses secondary data collected from previous Center protocols, all participants provided written informed consent for enrollment into the studies from which the present data were obtained. That study was reviewed and approved by our local Institutional Review Board (IRB). Cognitive Assessment All participants completed the MMSE,2 following standard administration and scoring procedures. If the score yielded from the “world” backward task was higher than that from the serial-sevens task, then the former was substituted for the latter in the total score and attention subcomponent. Participants were categorized as cognitively impaired if their MMSE score was ⱕ24.6 We also analyzed individual domains of MMSE items, including
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1. Orientation to time (season, date, day, month, year) 2. Orientation to place (floor, building, state, city, and country) 3. Registration (ball, flag, tree) 4. Attention (“serial-seven” subtractions or spelling “world” backwards [whichever was higher]) 5. Word recall (recalling ball, flag, tree) 6. Object naming (pencil, watch) 7. Sentence repetition (no ifs, ands, or buts) 8. Three-stage command (three-stage command) 9. Word reading (“Close your eyes”) 10. Writing (sentence) 11. Copying (copying pentagons)
Additional Measures We also examined data on participants’ marital status, history of alcohol abuse and/or dependence, schizophrenia subtype, age at onset of schizophrenia, duration of illness, and current daily dosages of neuroleptic medications. Neuroleptic dosages were converted to milligram chlorpromazine-equivalents (CPZE20). For the schizophrenia group, data were used from selected items in the Strauss Carpenter Prognostic Scale21 to evaluate recency of previous psychiatric hospitalizations, living situation (dichotomized to “unstructured”—in the community alone or with family member or friends, or “structured”— board-and-care), and frequency of social contacts (dichotomized to “once per week” or “less than once per week” based on the relative few individuals who reported gradations of social contacts). For a sizable subset of patients (sample sizes provided in the Results section), we also had information on the severity of psychopathology as measured with the Brief Psychiatric Rating Scale (BPRS22), the Positive and Negative Syndrome Scale (PANSS23), and/or the 17-item version of the Hamilton Rating Scale for Depression (Ham-D24). Severity of dyskinesia was evaluated with the Abnormal Involuntary Movement Scale (AIMS25). Statistical analyses. Demographic comparisons of patients versus NCs were conducted with t-tests for continuous variables and chi-square analyses for categorical variables. Stepwise linear regression was used to determine whether psychiatric diagnosis was a significant predictor of MMSE total score after con-
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Moore et al. trolling for education, gender, and ethnicity. Because there was significant skew among the MMSE scores for both the patients and NCs (which was not overcome by log, square root, or inverse functions), we used Mann-Whitney U tests to compare the MMSE performance among NCs versus schizophrenia patients. To examine the pattern of errors among the patients, we calculated the percentage of schizophrenia patients receiving less than a perfect score in a particular domain at cumulative levels of MMSE total score. Spearman’s correlations were calculated to evaluate the association between MMSE totals and the functional and psychiatric outcome variables in the patient group. Independent-sample t-tests or Pearson chi-square tests were used to evaluate differences on various functional and psychiatric variables for schizophrenia patients with normal versus impaired MMSE scores (MMSE ⱕ24). Because both age at onset of schizophrenia and total score on the AIMS were positively skewed, a log-transformation was applied to the age-at-onset variable, whereas the AIMS variable required a 1/XⳭC transformation before analysis. Statistical significance was defined as p ⱕ0.05 (two-tailed, where applicable).
RESULTS Schizophrenia patients were similar to the NCs in age, but had less education and were more likely to be white and male (Table 1). The difference in terms of education was expected and was within 1 education year. Patients were less likely to be married, and more likely to be living in a structured setting and TABLE 1.
have a history of alcohol abuse or dependence. Schizophrenia patients also had significantly lower mean MMSE totals than NCs (Table 1). This difference remained significant even after covarying for the effects of education, gender, and ethnicity (F[4, 241]⳱ 13.5; p ⬍0.001). In terms of specific MMSE domains, patients had worse performance on orientation, attention, word recall, three-stage command, writing, and construction; there were no significant differences in registration, object-naming, sentence repetition, and wordreading (Table 2). As shown in Table 3, regardless of the MMSE total score, very few patients missed items in the domains of registration, object naming, and word reading. Conversely, errors in word recall were common, even among the patients who only missed 1 of the 30 MMSE items (Table 3). When examining the domains with the greatest level of impairment at lower total MMSE scores, word recall and attention were the most likely impaired domains. Scores on the orientation to time and place, sentence repetition, writing, and copying items were slightly worse at lower levels of total MMSE score. As hypothesized, patients had the greatest difficulty with word-recall and attention regardless of the overall level of performance. Within the patient sample, Spearman correlations revealed a positive association of MMSE total with education (N⳱161; r⳱0.28; p ⬍0.001), and negative associations between MMSE total and severity of negative symptoms (PANSS Negative Symptom Subscale, N⳱98; r ⳱ –0.41; p ⬍0.001), and dyskinesia (AIMS Total: N⳱81; r ⳱ –0.18; p⳱0.04). Associations with other demographic, clinical, and functional vari-
Demographics of normal-comparison participants (NCS) and schizophrenia groups
Age, years Education, years Ethnicity: % non-white (N) Gender: % female (N) % Currently married (N) % With alcohol abuse or dependence (N) % Paranoid (N) Age at onset of schizophrenia, years Duration of illness, years Daily neuroleptic dose (mg CPZE) % in structured living facilities (N)
NCS (Nⴔ86)
Schizophrenia Patients (Nⴔ161)
t[df] or Pearson v2 [df] (N)
p
55.8 (9.2) 13.3 (2.3) 52.3% (45) 69.8% (60) 48.8% (42) 4.7% (4) N/A N/A N/A N/A 0% (0)
56.0 (8.7) 12.5 (2.5) 26.1% (42) 34.2% (55) 11.9% (19) 16.1% (26) 52% (84) 29.4 (12.5) 27.2 (12.7) 270 (865.5) 38.6% (62)
0.2 [245] ⳮ2.5 [245] 16.9[1] (N⳱247) 28.6[1] (N⳱247) 40.6[1] (N⳱245) 6.9[1] (N⳱247) N/A N/A N/A N/A 38.5[1] (N⳱207)
0.84 0.02 ⬍0.001 ⬍0.001 ⬍0.001 0.008 N/A N/A N/A N/A ⬍0.001
Note: Data are mean (standard deviation), unless otherwise indicated; N/A: not applicable; CPZE: chlorpromazine-equivalent (median is reported). Education variable was not normally distributed.
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MMSE and Schizophrenia ables were not significant. The majority of patients (80%) were taking at least one antipsychotic medication at the time of testing, and 28% (38/127) were on an atypical antipsychotic as their primary antipsychotic medication. There was no significant difference on the MMSE total score between those who were taking antipsychotic medications and those who were not (t[1,153]⳱1.3; p⳱0.19), nor was there a significant correlation between antipsychotic dose and performance on the MMSE (r ⳱ –0.12; p⳱0.13). Alcohol abuse or dependence was not associated with poorer MMSE total scores in the patient group (t[1,159] ⳱ –0.32; p⳱0.75). Using the pre-established cutoff score (MMSE total ⱕ24 defined as impaired), 37 (23%) of the patients, but none of the NCs had an impaired-range MMSE score (N⳱247; v2[1]⳱23.2; p ⬍0.001). Relative to those with an unimpaired MMSE total score, the cognitively impaired patients had less education, were less likely to be married, were more likely to be living in a structured setting, and had more severe negative symptoms (Table 4). Only one patient had an MMSE score ⱕ10.
DISCUSSION Consistent with our first hypothesis, schizophrenia patients had worse MMSE total scores than NCs. Within the schizophrenia group, the most frequently impaired cognitive domains were Word Recall and Attention, confirming our second hypothesis. Our final hypothesis was partially supported. Among the TABLE 2.
patients, impaired MMSE scores were associated with less education, a greater likelihood of being in a structured living situation, decreased likelihood of being currently married, and having worse negative symptoms; however, no association was observed between impaired MMSE scores and the frequency of social contacts. Whereas 23% of our sample had MMSE scores below 24, severe cognitive impairment (MMSE ⱕ1026) was very rare; only one patient in our sample had an MMSE score in that range. Among chronically institutionalized schizophrenia samples, there has been one report showing that 17% of patients had MMSE total scores of 10 or less12 and another indicating that the average MMSE score for inpatients was approximately 10.5.13 This points to considerable differences in cognitive functioning that may be observed in institutionalized versus community-dwelling schizophrenia patients. AD patients with mild-to-moderate impairment show difficulty in the areas of word recall, attention, and orientation8,9 that are similar to the impairment patterns seen among the middle-aged and older schizophrenia outpatients in our sample. However, late-stage AD patients have deficits in sentence repetition, object naming, and following commands,8 whereas none of the schizophrenia patients showed object naming difficulties, and impairments in sentence repetition and following commands were, respectively, the fifth and eighth most likely impaired domains among the most severely impaired individuals in our study (those with MMSE totals between 8 and 24). Further research with a larger sample of
MMSE total and domain scores for normal-comparison participants (NCS) and schizophrenia patients
Orientation to Time Orientation to Place Registration Attention Word Recall Object-Naming Sentence Repetition 3-Stage Command Word-Reading Writing Copying MMSE Total
Maximum Score
NCS (Nⴔ86)
Schizophrenia Patients (Nⴔ161)
Mann-Whitney U or z-Score
p
5 5 3 5 3 2 1 3 1 1 1 30
4.97 (0.18) 4.99 (0.11) 3.0 (0) 4.74 (0.57) 2.47 (0.84) 2.0 (0) 0.86 (0.35) 2.98 (0.15) 1.0 (0) 1.0 (0) 0.92 (0.28) 28.92 (1.25)
4.67 (0.78) 4.71 (0.80) 2.98 (0.24) 3.88 (1.63) 2.02 (1.08) 2.0 (0) 0.80 (0.40) 2.85 (0.44) 0.98 (0.16) 0.89 (0.31) 0.76 (0.43) 26.55 (3.72)
ⳮ3.8 ⳮ3.8 ⳮ0.7 ⳮ4.2 ⳮ3.1 0 ⳮ1.2 ⳮ2.7 ⳮ1.5 ⳮ3.1 ⳮ3.0 ⳮ5.7
⬍0.001 ⬍0.001 0.47 ⬍0.001 0.002 1.0 0.25 0.008 0.14 0.002 0.003 ⬍0.001
Note: Data are mean (standard deviation), unless otherwise indicated; N/A: A t-test or chi-square could not be computed for this variable because the standard deviations for both groups was 0. MMSE: Mini-Mental State Exam (minimum score for all MMSE domains is 0).
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Note: MMSE: Mini-Mental State Exam. Orientation to Time: maximum score ⳱ 5; Orientation to Place: maximum score ⳱ 5; Registration: maximum score ⳱ 3; Attention: maximum score ⳱ 5; Word Recall: maximum score ⳱ 3; Object-Naming: maximum score ⳱ 2; Sentence Repetition: maximum score ⳱ 1; 3-Stage Command: maximum score ⳱ 3; Word-Reading: maximum score ⳱ 1; Writing: maximum score ⳱ 1; Copying: maximum score ⳱ 1.
0% 9% (4/45) 15% (9/61) 18% (14/80) 21% (18/87) 25% (24/97) 25% (27/106) 26% (29/110) 26% (29/113) 27% (32/117) 31% (38/124) 54% (20/37) 5% (1/21) 7% (3/45) 7% (4/61) 5% (4/80) 6% (5/87) 6% (6/97) 10% (11/106) 10% (11/110) 11% (13/113) 11% (13/117) 14% (17/124) 32% (12/37) 14% (3/21) 0% 9% (4/45) 0% 12% (7/61) 0% 11% (9/80) 0% 14% (12/87) 0% 14% (14/97) 0% 13% (14/106) 0% 14% (15/110) 0% 13% (15/113) 0% 15% (17/117) 0% 16% (20/124) 3% (4/124) 22% (8/37) 11% (4/37) 0% 13% (6/45) 16% (10/61) 19% (15/80) 18% (16/87) 21% (20/97) 20% (21/106) 22% (24/110) 21% (24/113) 22% (26/117) 26% (32/124) 43% (16/37) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 52% (11/21) 55% (25/45) 57% (35/61) 65% (52/80) 66% (57/87) 68% (66/97) 66% (71/106) 67% (74/110) 68% (77/113) 68% (80/117) 70% (87/124) 81% (30/37) 19% (4/21) 22% (10/45) 30% (18/61) 34% (27/80) 36% (31/87) 42% (41/97) 47% (50/106) 49% (54/110) 50% (57/113) 52% (61/117) 55% (68/124) 100% (37/37) 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 1% (1/124) 3% (1/37) 0% 2% (1/45) 2% (1/61) 6% (5/80) 8% (7/87) 10% (10/97) 16% (17/106) 17% (19/110) 17% (43/113) 18% (21/117) 23% (28/124) 54% (20/37) 21 45 61 80 87 97 106 110 113 117 124 37 29 28–29 27–29 26–29 25–29 24–29 23–29 22–29 21–29 20–29 8–29 8–24
10% (2/21) 20% (9/45) 25% (15/61) 26% (21/80) 25% (22/87) 24% (23/97) 23% (24/106) 24% (26/110) 24% (27/113) 26% (30/117) 28% (35/124) 35% (13/37)
Writing Word Reading 3-Stage Command Sentence Repetition Object Naming Word Recall Attention Registration Orientation to Place Orientation to Time N MMSE Total Score
TABLE 3.
Percentage of schizophrenia patients at cumulative levels of MMSE total score (row) who received less than a perfect score in a particular domain
Copying
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schizophrenia patients with severe cognitive impairment would be useful to help determine the degree to which such differences reflect overall level of cognitive impairment, versus disorder-specific cognitive patterns. Applying the commonly used MMSE cutoff score of ⱕ24 in this study, 23% of the patients were classified as impaired. Studies from our group and others using more comprehensive neuropsychological test batteries show that approximately 75% of schizophrenia patients have at least mild-to-moderate cognitive deficits.27,28 The above studies differ in their approach to detecting impairment (the current study uses a simple cutoff score, whereas previous studies required impairment in multiple cognitive domains); however, the data suggest that an MMSE cutoff score of ⱕ24 is insensitive to some of the less-severe cognitive deficits often present in patients with this disorder. Greater sensitivity could be achieved by using a higher cutoff score, although this would come at the cost of decreased specificity. Thus, the MMSE is likely to be most useful as a means of efficiently identifying patients with moderate-to-severe cognitive deficits, rather than for screening out those with mild cognitive impairment. Of interest, however, word recall was often impaired even among patients with normal-range MMSE total scores; the word recall task in the MMSE might itself be a useful procedure for cognitive screening. Because those with the most severe deficits are likely to have the greatest functional dependence, the full MMSE may still be useful in identifying those individuals. It must be acknowledged that the MMSE was not explicitly designed for comparison of individual cognitive domains (different domains have different numbers of items with unknown equivalence in sensitivity to their respective cognitive constructs). Nonetheless, it is of interest that the domains we found to be impaired (Word Recall and Attention) are among those most commonly reported to be affected in studies of schizophrenia patients that make use of comprehensive neuropsychological batteries.16,17 Another limitation of the MMSE for use in schizophrenia patients is that it does not explicitly measure executive skills, which are frequently impaired even in schizophrenia patients with preserved intellect29 and may be particularly sensitive to cognitive problems in older schizophrenia patients.30 It is possible, however, that executive functioning skills may influ-
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MMSE and Schizophrenia ence performance on word recall and attention.31,32 Future studies are needed to develop brief measures that are sensitive and specific to the mild cognitive deficits typical in schizophrenia. In conclusion, middle-aged and older schizophrenia outpatients display worse performance on the MMSE than NCs. Schizophrenia patients had the most frequent difficulties in recall and attention. Also, MMSE scores were related to severity of negative symptoms and psychosocial functioning (education, structured living situation, and marital status). Thus, despite its known limitations, given the ease of administering and scoring the MMSE, wider use of the MMSE as part of clinical care may be warranted. PaTABLE 4.
tients scoring in the unimpaired range may still have undetected cognitive deficits, but those categorized as impaired are likely to have functionally-relevant cognitive deficits that might suggest a need for further neuropsychological evaluation. We thank the patients who participated in this study. We also thank Shah Golshan, Ph.D., and Gosia Kubiak, M.Sc., for their statistical consultation. Charles F. Reynolds III, M.D., served as the action editor for this manuscript. This work was supported, in part, by National Institute of Mental Health grants MH19934-10, MH5910105, and MH66248-02, and by the Department of Veterans Affairs.
MMSE impairment levels for schizophrenia patients (MMSE impairment cutoff score: ⱕ24)
Age, years Education, years Ethnicity: % non-white (N) Gender: % female (N) % Currently married (N) % with alcohol abuse or dependence (N) Age at onset of schizophrenia, years a Duration of illness, years % in structured living facilities (N) % with a hospitalization within last year (N) % with social contacts ⬎ once/week (N) BPRS (1–18) PANSS Positive score PANSS Negative score PANSS general psychopathology Ham-D (1–17) Total AIMS a
MMSE ⬎24 (Nⴔ124)
MMSE ⱕ24 (Nⴔ37)
t[df] or Pearson v2[df] (N)
p
55.5 (8.5) 13.0 (2.1) 23.4% (29) 31.5% (39) 15.4% (19) 15.3% (19) 29.8 (12.5) 26.2 (12.5) 31.0% (31) 35.3% (24) 50.0% (43) 33.4 (8.2) 15.9 (6.1) 15.4 (5.7) 30.1 (6.7) 9.4 (5.5) 2.7 (2.9)
57.7 (8.9) 10.9 (3.1) 35.1% (13) 43.2% (16) 0% (0) 18.9% (7) 28.0 (12.5) 30.6 (13.1) 60.6% (20) 40.0% (10) 41.7% (10) 33.2 (8.1) 15.3 (5.2) 19.2 (6.6) 31.1 (6.5) 9.4 (5.0) 3.5 (2.8)
ⳮ1.4 [159] 4.7 [158] 2.0 [1] (N⳱161) 1.8 [1] (N⳱161) 6.3 [1] (N⳱159) 0.3 [1] (N⳱161) 0.9 [144] ⳮ1.8 [146] 9.2 [1] (N⳱133) 0.2 [1] (N⳱93) 0.5 [1] (N⳱110) 0.1 [145] 0.4 [96] ⳮ2.8 [96] ⳮ0.7 [95] ⳮ0.03 [145] 1.8 [139]
0.18 ⬍0.001 0.15 0.18 0.01 0.60 0.35 0.07 0.001 0.68 0.47 0.92 0.66 0.006 0.50 0.98 0.07
Note: Data are mean (standard deviation), unless otherwise indicated; MMSE: Mini-Mental State Exam; AIMS: Abnormal Involuntary Movement Scale; BPRS: Brief Psychiatric Rating Scale; Ham-D: Hamilton Rating Scale for Depression; PANSS: Positive and Negative Syndrome Scale. Raw scores are reported for interpretation purposes. a Because both age at onset of schizophrenia and total score on the AIMS were positively skewed, a log-transformation was applied to the age-at-onset variable, whereas the AIMS variable required a 1/XⳭC transformation before analysis.
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