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The association between adaptive and cognitive deficits in geriatric chronic schizophrenic patients
SCHIZOPHRENIA RESEARCH ELSEVIER
Schizophrenia Research 27 (1997) 211 218
The association between adaptive and cognitive deficits in geriatric chronic schizophrenic patients Philip D. Harvey *, Denis Sukhodolsky, Michael Parrella, Leonard White, Michael Davidson Department of Psychiatry, Mount Sinai School of Medicine, New York, N Y 10029, USA
Abstract
Cognitive impairments have been shown to predict impairments in adaptive functioning in patients with chronic schizophrenia and to be more predictive of overall outcome than positive or negative symptoms of the illness. Both adaptive and cognitive impairments are multidimensional, and it is possible that correlations between these domains may be limited to certain aspects of these functions. In this study, 208 geriatric patients with chronic schizophrenia were examined with a cognitive battery and assessed with a structured scale to determine the extent of their adaptive functions. Instrumental and social skills deficits were more strongly correlated with cognitive impairments than with the severity of undercontrolled behavior. Each of the cognitive measures was correlated with global social-adaptive deficits, with minimal variation in the magnitude of correlations. These results suggest that interventions should be individually targeted to cognitive-adaptive impairments and undercontrolled behavior. © 1997 Elsevier Science B.V. Keywords: Cognitive impairment; Skills deficit; Chronic schizophrenia
I. Introduction
Cognitive impairments are c o m m o n in schizophrenia (Gold and Harvey, 1993) and are more severe in patients with a more negative course of illness and chronic hospitalization (Davidson et al., 1995; Perlick et al., 1992). Similarly, deficits in adaptive functioning are c o m m o n in patients with a p o o r outcome (Keefe et al., 1987, 1996; Mueser et al., 1991 ), with the severity of deficits in adaptive functioning, and p o o r outcome previously reported being correlated with impairments in cognitive functioning (Breier et al., 1991; Harvey et al., * Corresponding author. Tel: 212-241-6637; fax: 212-860-3945; e-mail: 73414.2311@ compuserve.corn 0920-9964/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PH S0920-9964 (97) 00068-6
1997). Although positive symptoms of schizophrenia are severe in poor-outcome schizophrenic patients, the severity of these symptoms in verypoor-outcome patients has consistently been reported to be no greater than in patients with a less chronic course of illness (Keefe et al., 1987) and to be unrelated to the severity of cognitive impairments (Addington et al., 1991; Breier et al., 1991; Davidson et al., 1995). Additional aspects of schizophrenia other than cognitive and adaptive impairments contribute to extended hospital stays. In a recent study of over 800 geriatric psychiatric inpatients followed longitudinally during a period of downsizing, we found that elevations in belligerence and hostility, but not cognitive impairments, negative symptoms or
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psychotic symptoms, predicted failure of patients to be referred to alternative levels of care in the community (White et al., in press). Similar results were recently reported by Anderson and Trieman (1996), who found that behavioral disturbances, but not cognitive impairment, predicted referral to higher levels of care in geropsychiatric services. Even within the domain of adaptive deficits, there are multiple dimensions that could have differential prognostic importance and that possibly require differential interventions for successful treatment. For example, instrumental deficits might have a more adverse impact than social deficits in some types of community placements, and undercontrolled behavior might be manageable only in a secure ward at a psychiatric hospital. In the same vein, it is possible that various aspects of cognitive functioning could have a differential relationship with adaptive impairment. This possibility was explored in detail by Green (1996), who demonstrated that three types of cognitive impairment-vigilance deficits, memory impairments, and executive functioning deficits--were more strongly correlated than other aspects of cognitive functioning with poor response to attempts at remediation of adaptive deficits in schizophrenia. Thus, 'global' cognitive impairment was less important than specific cognitive impairments in the prediction of response to behavioral treatments. In this report, we present the results of a study examining differential relationships between cognitive and adaptive deficits in geriatric inpatients with chronic schizophrenia. These patients were evaluated for adaptive deficits with a structured rating instrument, the Social-Adaptive Functioning Evaluation (SAFE) scale (Harvey et al., 1997) and tested with a neuropsychological battery. The 17 individual items from the SAFE scale and the three factors derived during the development of the scale were correlated with a composite measure of cognitive impairment. Total adaptive deficit was correlated with each of the individual performance measures in the neuropsychological battery. A previous study has shown that SAFE scale total scores were significantly correlated with negative and cognitive symptoms of schizophrenia, but not with positive symptoms (Harvey et al., 1997). When the differential contri-
butions of global cognitive impairment and negative symptoms to SAFE scale total scores were examined by regression analysis, cognitive impairments were correlated with SAFE scale scores, but negative symptoms contributed no additional variance above that associated with the correlation between cognitive impairments and negative symptoms. Since some of those patients also participated in this study, those analyses were not repeated again here. The goal of this study was to determine the answers to the following questions: (1) Are there differences in the relationship of overall estimates of cognitive functioning and various aspects (e.g., social skills, instrumental skills, impulsive behavior) of adaptive functioning deficit in poor-outcome geriatric patients with schizophrenia? (2) Are various aspects of cognitive-neuropsychological functioning (e.g., memory, verbal skills) differentially related to overall adaptive deficits? (3) Can any individual measures of cognitive functioning adequately predict the level of adaptive deficit?
2. Methods
2.1. Subjects All patients were participants in a large-scale program of research on cognitive functioning and clinical symptoms in geriatric chronic psychiatric inpatients. Diagnostic assessments were performed by research staff members and a structured consensus procedure was employed in order to generate DSM-III-R diagnoses of schizophrenia. The entire assessment procedure for that study was published recently and all subjects in this study were diagnosed and assessed with that procedure (Davidson et al., 1995, 1996). Patients were excluded for the presence of any disorders that ruled out DSMIII-R schizophrenia, including mental retardation, substance dependence, neurological problems, and other psychiatric diagnoses. Subjects in this study consisted of all geriatric patients in the institution
P. D. Harvey et al. / Schizophrenia Research 27 (1997) 211 218
who met diagnostic criteria and could be evaluated with the neuropsychological battery. Forty-seven patients with Mini-Mental State Exam (MMSE) scores of 0 could not be tested with the entire cognitive battery and were excluded from participation in this study. A total of 254 geriatric schizophrenic patients provided complete cognitive assessment data. Of these patients, 36 were not completely assessable with the adaptive functioning ratings owing to limitations in physical ability or lack of opportunity to perform certain behaviors. Because this is a validity study, those patients were eliminated from the data analysis, leaving a total of 208 eligible subjects. Patients had a mean (_+_SD) age of 75.8+8.2 years (range, 65 96); 44% of subjects were male. All had been hospitalized for at least 10 consecutive years (range, 11-58) and none had an onset age later than 45 years or earlier than 16years. Patients had completed 9.7+3.17 years of formal education (range, 6 14). The average age at first psychiatric hospitalization was 30.7+ 13.7 years (range, 16 45).
2.2. Cognitive assessment All subjects were examined with a variety of clinical and cognitive assessments. Patients were examined with the MMSE (Folstein et al., 1975) and the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Cognitive Battery (Morris et al., 1989). This battery, described previously by Welsh et al. (1992), examines a variety of functions affected by Alzheimer's Disease and other progressive dementing conditions. We have previously demonstrated the reliability and validity of this battery in assessing patients with chronic schizophrenia (Davidson et al., 1996; Harvey et al., 1996).
2.3. CERAD battery 2.3.1. Word list learning and delayed recall A 10-item list of words is presented to the subject on three separate learning trials. After each trial, free recall of the list is required of the subject. After a delay, filled by the Praxis Examination
2I 3
described below, recall of the word list is required. Dependent variables for this report were the number of words recalled on the first learning trial, the total number of words recalled over three learning trials, and the proportion of words learned by trial three that were recalled at the delayed recall (savings).
2.3.2. Praxic drawings Four drawings (circle, diamond, overlapping rectangles, and cube) are presented to the subject, who is instructed to copy them exactly. Reproductions are scored according to predetermined criteria. The dependent variable is the total score for all four drawings. 2.3.3. Modified Boston Naming Test Subjects are presented with 15 line drawings and asked to name the object depicted. Of the 15 drawings, five are of objects with high frequency of occurrence in spoken English, five of moderate frequency, and five of low frequency. The dependent variable is the total number of correct namings. 2.3.4. Category fluency Subjects were asked to name as many animals as they could in a 1-min period. The dependent variable is the number of unique animals named. 2.4. Adaptive functioning All patients were rated with the Social-Adaptive Functioning Evaluation (SAFE) scale (Harvey et ai., 1997) by trained raters from the research team (the SAFE scale is available from the authors). These raters were different from those performing the cognitive assessment. The SAFE scale is a structured 17-item scale designed to assess multiple aspects of adaptive functioning in geriatric inpatients. Ratings are generated for the patients' behavior 'on average' for the past month on a 5-point (0-4) scale, based on the raters' condensation of observation of a patient reading of the chart and a caregiver report. Adaptive deficits are given a score of 0 if there is no impairment, and 4 if there is severe and incapacitating impairment. For example, for item 11, instrumental social skills, mild
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impairment (severity of 1.0) is defined as follows: "The patient is often able to achieve the instrumental goals of his interactions. The patient may occasionally ask an inappropriate person for something. Social skill problems may occasionally limit the patient's ability to achieve instrumental goals (e.g., the patient demands something rather than requests it, he stands inappropriately close to the other person, he speaks in a low voice tone)." Whereas severe impairment (3.0) is defined as follows: "The patient rarely attains instrumental goals of social interactions, because of poor social skills and misperception of social roles. The patient approaches others occasionally to achieve instrumental goals." Patients who had no opportunity to perform behaviors in a skills domain (e.g., no relatives called on the telephone; restricted to ward and not permitted to move around the hospital grounds) were not rated on that item and were excluded from the analyses. At the time of the assessment, raters were unaware of the results of the cognitive assessment of the patients. Interrater reliability, that is, intraclass correlations of the ratings for the individual items of the scale, based on 50 patients, ranged from a low of 0.87 to 0.98 (all p <0.001) and 1-week test-retest reliability ranged from 0.59 to 0.86. Total score intraclass correlations were 0.99 for both interrater and test-retest reliability. Factor analyses during the development of the scale revealed three factors, labeled 'Instrumental and self-care'; 'Impulsivity'; and 'Social functions'. The dependent variables for this study, depending on the analysis, were the item, total, or factor scores.
2.5. Data analyses Although there was a reasonably large overall population in the study, analyses were performed as conservatively as possible in order to reduce the overall number of correlations computed. Total scores on the SAFE scale were used for correlation with individual cognitive functioning dependent variables, in order to reduce the number of correlations computed. Similarly, a composite index of cognitive impairment was created for use in the correlational analyses examining the individual SAFE items and the SAFE factor scores.
2.5.1. Creation of a composite measure of cognitive impairment Total Boston Naming Test scores, total Praxis test scores, Word List Trial 1 scores, Word List Total Learning scores (Trials 1-3), Word List Savings scores (Delayed Recall/Trial 3), and Category Fluency scores were all standardized by creating z-scores on the basis of the performance of the entire sample of patients. A single composite was created by averaging these individual z-scores (the correlations between the individual cognitive dependent variables were all greater than Pearson r=0.60). M M S E scores were not entered into the composite measure because of the redundancy created by including a global functioning scale with individual neuropsychological tests. 2.5.2. Correlational analysis The 17 individual SAFE items were correlated with the composite measure of cognitive functioning described above with Pearson correlations. Similarly, SAFE factor scores and total scores were also correlated with the composite cognitive functioning measure. The individual cognitive functioning measures were correlated with total SAFE scores with Pearson correlations. 2.5.3. Regression analyses After the correlational analyses, stepwise regression analyses were computed in order to identify the best predictors of the criterion variables of interest. In the case of the relationship between SAFE scale scores and composite cognitive impairments, the variables used to predict the cognitive composite were the three SAFE factor scores. For the prediction of SAFE total scores, the predictors were the six individual cognitive functioning measures.
3. Results
Table 1 presents the scores on the SAFE scale and the correlation between individual SAFE scale items, factor scores, and total scores, and the composite measure of cognitive functioning. Although all correlations were statistically significant (all p values <0.006, uncorrected), two of
P. D. Harvey et al. / Schizophrenia Research 27 (1997j 211-218
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Table 1 Mean (_+SD) scores on the Social-Adaptive Functioning Evaluation scale (SAFE) and correlations of the SAFE scores with global cognitive functioning Score
Pearson r a
Factor SC SC SC SC SC SC IC IC SF SF SF SF SF SF SF SF IC
Bathing and grooming Clothing and dressing Eating, feeding and diet Money management Neatness and maintenance Orientation and mobility Impulse control Respect for property Communication skills Conversational skills Instrumental social skills Social appropriateness Social engagement Friendships Recreation and leisure Participation in hospital activities Cooperation with treatment
2.02 ± 1.17 1.87 + 1.09 1.46 _+0.95 2.97 + 1.50 3.32 _+ 1.25 3.13 ± 1.12 1.19 ± 1.23 1.36 + 1.34 3.36+ 1.22 2.26 ± 1.26 1.59 _+ 1.40 1.57 ± 1.04 2.59+_0.99 2.97 ± 1.11 2.45 ± 1.09 2.28 + 1.10 1.59 _+0.79
- 0.578 - 0.521 - 0.526 - 0.586 - 0.383 - 0.498 - 0.189 - 0.413 -0.517 - 0.684 -0.657 -0.435 -0.48l - 0.451 - 0.488 - 0.405 - 0.202
Factor 1 (Instrumental and self-care) Factor 2 (Impulse control ) Factor 3 (Social functions)
2.63 +0.91 1.57 +_0.83 2.23 _+0.89
-0.688 --0.372 -0.667
39.08 ± 13.24
-0.719
SAFE total score
SC =Self care; SF =Social functions; IC = Impulse control. aAll p values _<0.006.
the SAFE scale items were notably less strongly correlated with cognitive functioning than the other items: impulse control and cooperation with treatment. These items are most strongly loaded on the impulse control factor, which was also considerably less strongly correlated with cognitive functioning than the other two factors, z tests of the significance of the difference between correlations found that the larger of these two correlations, 'cooperation with treatment', was significantly smaller than the next smallest correlation ('neatness and maintenance') at p<0.01. Similarly, the correlation between the impulse control factor score and the composite measure of cognitive impairment was also significantly (p<0.001) smaller than the correlation between the social functions factor and the cognitive impairment composite score. In the stepwise regression analysis, the overall analysis was significant, R2=0.53, F(2 205)= 116.51, p<0.001.
Both 'Instrumental and self-care' and 'Social functions' accounted for significant variance increments in the cognitive composite score, while 'Impulse control' did not enter the regression analysis. These findings indicate that cognitive impairments are more strongly correlated with skills deficits, both social and instrumental, than with behavioral undercontrol in these subjects. Table 2 presents the scores on the cognitive neuropsychological measures and their correlation with total SAFE scale scores. Of all the individual cognitive items, the smallest correlation (delayed recall savings) with adaptive deficits still accounted for over 22% variance in SAFE scale total scores and was significant at p<0.001. Overall cognitive composite scores and MMSE scores were very strongly correlated with SAFE scale total scores. In the stepwise regression analysis, the overall analysis was statistically significant, F(4,203) = 44.90, p<0.001, R2=0.53. Of the six individual
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Table 2 Mean (± SD) scores on tests of cognitive functioning and correlations with Social-Adaptive Functioning Evaluation scale (SAFE) total scores
Boston Naming Test Constructional praxis Word List Learning Trial One Word List Total Learning Word List Savings Verbal Fluency Test total M M S E total Cognitive composite score
Score
Pearson r a
7.59+_5.18 3.88 _+3.45 1.52 + 1.83 6.80_+6.66 0.26_+0,41 10.89 _+ 13.00 14.64_+9,06
-0.577 - 0.623 -0.540 -0.640 -0.470 - 0.648 -0.729 -0.719
aAll p values _<0.00l.
cognitive items, only Boston Naming total scores and Word List Learning Delayed Recall Savings scores did not enter the regression on a significant basis. Thus, these results indicate that there is no individual cognitive test that predicts the level of adaptive deficit considerably better than the others, and that composite measures of cognitive dysfunction are highly associated with the overall level of social and adaptive deficit seen.
4. Discussion
Adaptive deficits in poor outcome geriatric patients with schizophrenia are multidimensional, as evidenced by their differential patterns of correlation with cognitive impairments. Impulsivity is less strongly associated with cognitive impairments than social and instrumental skills deficits, whereas in the domain of cognitive impairments, nearly all aspects of functioning measured in the study contributed independent variance to deficits in adaptive skills. These results suggest that social and adaptive skills deficits in geriatric chronic schizophrenic patients are independently related to deficits in learning, verbal skills, and praxic functions, with no single aspect of cognitive impairment being a much better predictor of the level of global adaptive deficit. Before proceeding to the implications of these findings, a review of the limitations of the study is important. These are very-bad-outcome patients
who are not typical of all geriatric patients with schizophrenia. It is well known that better-outcome geriatric patients with schizophrenia have markedly reduced cognitive impairments (Heaton et al., 1994). Impulse control deficits were markedly reduced in their level of severity compared to adaptive functioning deficits, which could have affected correlations with variables from other domains. This is a brief cognitive assessment oriented at dementia and does not include some of the typical tests found to correlate with adaptive deficit in younger patients (e.g., vigilance and the Wisconsin Card Sorting Test). Inclusion of these tests might strengthen the present pattern of results, or it might even increase the correlation between impulsivity and cognitive impairment. All of the cognitive measures were quite highly correlated with each other, limiting the ability of the analyses to find differential correlations between individual cognitive measures and adaptive functioning deficit. Finally, the impulsivity factor has the fewest items; consequently, it might simply be less strongly correlated with adaptive deficits, because it is less reliable. There are two main implications of these findings. Even in patients at the far end of the distribution of cognitive impairment and adaptive deficit, there are powerful relationships between these two aspects of schizophrenia. These findings underscore the likely merit of cognitive enhancement on adaptive functioning, even in patients who are seriously impaired. Since behavioral cognitive rehabilitation approaches are presently of doubtful merit (Bellack, 1992; Green, 1993), pharmacological interventions seem to be the most promising area for intervention. Whereas typical neuroleptic medication has had very poor results for improving the critical cognitive impairments in schizophrenia (Medalia et al., 1988), other than certain attentional functions (Serper et al., 1994), some recent positive results involving amphetamine (Goldberg et al., 1991), clozapine (Lee et al., 1994) and risperidone (Gallhofer et al., 1996) all suggest that these agents may have promise for the future. Systematic trials of the effects of these medications and augmentation strategies, including patients at all levels of severity, are clearly called for.
P.D. Harvey el al. / Schizophrenia Research 27 (1997) 211 218
The second implication is that there are two generally independent aspects of social-instrumental deficits in geriatric schizophrenic patients with a poor course of illness: adaptive deficits and behavioral undercontrol. These findings are consistent with earlier research findings that aggressivity extends acute admission for psychogeriatric patients (Mulsant et al., 1993) and that impulsive behavioral undercontrol on the part of chronic geropsychiatric inpatients was a much stronger predictor of being hard to place (Anderson and Trieman~ 1996; White et al., in press) than cognitive or adaptive impairments. Since cognitive impairments were found to be relatively weakly related to the severity of impulsive behaviors, it is unlikely that a single treatment strategy would be effective for both of these dimensions of schizophrenia. These findings suggest that pharmacologic interventions for geriatric inpatients require two independent, and possibly competing, goals. Many current interventions that are used in clinical settings to reduce belligerence (e.g,, benzodiazepines or low-potency neuroleptics with anticholinergic effects) have the potential to adversely affect cognitive functioning and, possibly, social and adaptive skills. Thus aggressive pharmacologic treatment of undercontrolled behavior appears to have the potential to exacerbate cognitive impairments and skills deficits. Behavioral interventions may have more promise in this area. Prioritizing these competing needs is a clinical goal that seems critical for reducing the incidence of adverse outcomes in psychogeriatric patients. Future research in pharmacologic treatment of schizophrenia should adopt a biphasic approach toward outcome in order to measure the success of interventions on these two domains of functioning. An additional useful direction would be the application of controlled clinical trials designed to examine combined pharmacological and behavioral intervention strategies, in order to optimize outcome across these two domains.
Acknowledgment This research was supported by grant number MH46436 awarded to Dr. Davidson. The authors
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thank the following staff members who contributed to this study: Janice McCrystal, Stephanie Bowler, Rita Ohsiek, Susan Frick and Cynthia Blum.
References Addington, J., Addington, D., Matticka-Tyndale, E., 1991. Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophr. Res. 4, 123 134. Anderson, J., Trieman, N., 1996. The TAPS Project 21: functional and organic co-morbidity and the effect of cognitive and behavioral disability on the placement of elderly psychiatric inpatients: a whole hospital survey. Int. J. Geriatr. Psychiatry t0, 959 966. Bellack, A.S.. 1992. Cognitive rehabilitation for schizophrenia: is it possible? Is it necessa~'? Schizophr. Bull. 18, 43-50. Breier, A., Schreiber, J.L., Dyer, J. et al., 1991. National Institute of Mental Health longitudinal study of schizophrenia: prognosis and predictors of outcome. Arch. Gen. Psychiatry 48, 239--246. Davidson, M., Harvey, P.D., Powchik, P. et al., 1995. Severity of symptoms in geriatric chronic schizophrenic inpatients. Am. J. Psychiatry 152, 197-207. Davidson, M., Harvey, P.D., Welsh, K. et al., 1996. Cognitive impairment in old-age schizophrenia: a comparative study of schizophrenia and Alzheimer's disease. Am. J. Psychiatry 153, 1274 1279. Folstein, M.F., Folstein, S.E., McHugh, P.K., 1975. Minimental state: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatric Res. 12, 189-198. Gallhofer, B., Bauer, U., Lis, S., et al., 1996. Cognitive dysfunction in schizophrenia: comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs. Eur. Neuropsychopharmacol. 6, $2-13-$2-20. Gold, J.M., Harvey, P.D.. 1993. Cognitive deficits in schizophrenia. Psychiatr. Clin. North Am. 16, 295 312. Goldberg, T.E., Bigelow, L.B., Weinberger, D.R. et al., 1991. Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia. Am. J. Psychiatry 148, 78 84. Green, M.F., 1993. Cognitive remediation in schizophrenia: Is it time yet? Am. J. Psychiatry 150, 178 187. Green, M.F., 1996. What are the functional consequences of neurocognitive deficits in schizophrenia? Am. J. Psychiatry 153, 321-330. Harvey, P.D., Davidson, M., Mueser, K. et al., 1997. The Social Adaptive Functioning Evaluation: an assessment measure for geriatric psychiatric patients. Schizophr. Bull. 22, 223- 231. Harvey, P.D., Lombardi, J.. Leibman, M. et al., 1996. Performance of geriatric chronic schizophrenic patients on cognitive neuropsychological measures sensitive to dementia. Int. J. Geriatr. Psychiatry 11,621 627. Heaton, R.K., Paulsen, J.S., McAdams, L.A. et al., 1994. Neuropsychological deficits in schizophrenics. Relationship
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to age, chronicity, and dementia. Arch. Gen. Psychiatry 51, 469-476. Lee, M.A., Thompson, P.A., Meltzer, H.Y., 1994. Effects of clozapine on cognitive function in schizophrenia. J. Clin. Psychiatry 55, 82 87. Keefe, R.S.E., Frecksa, E., Apter, S. et al., 1996. Clinical characteristics of Kraepelinian schizophrenia: a replication and extension of previous findings. Am. J. Psychiatry 153, 806 811. Keefe, R.S.E., Mohs, R.C., Losonczy, M.F. et al., 1987. Characteristics of very poor outcome schizophrenia. Am. J. Psychiatry 144, 889 895. Medalia, A., Gold, J., Merriam, A., 1988. The effects of neuroleptics on neuropsychological test results of schizophrenics. Arch. Clin. Neuropsychol. 3~ 249 271. Morris, J.C., Heyman, A., Mohs, R.C. et al., 1989. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Neurology 39, 1159-1165. Mueser, K.T., Bellack, A.T., Douglas, M.S. et al., 1991. Prediction of social skills acquisition in schizophrenic and major affective disorder patients from memory and symptomatology. Psychiatry Res. 37, 281-296.
Mulsant, B.H., Stergiou, A., Keshavan, M.S. et al., 1993. Schizophrenia in late life: elderly patients admitted to an acute care hospital. Schizophr. Bull. 19, 709-722. Perlick, D., Mattis, S., Statsny, P. et al., 1992. Neuropsychological discriminators of long-term inpatient or outpatient status in chronic schizophrenia. J. Neuropsychiatry Clin. Neurosci. 4, 428-434. Serper, M.R., Davidson, M., Harvey, P.D., 1994. Attentional predictors of clinical change during neuroleptic treatment. Schizophr. Res. 13, 65-71. Welsh, K.A., Butters, N., Hughes, J.P. et al., 1992. Detection and staging of dementia in Alzheimer's disease: Use of neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease. Arch. Neurol. 49, 448-452. White, L., Parrella, M., McCrystal-Simon, J. et al., in press. Characteristics of elderly psychiatric patients retained in a state hospital during downsizing: a prospective study with replication. Int. J. Geriatr. Psychiatry.
Schizophrenia Research 27 (1997) 211 218
The association between adaptive and cognitive deficits in geriatric chronic schizophrenic patients Philip D. Harvey *, Denis Sukhodolsky, Michael Parrella, Leonard White, Michael Davidson Department of Psychiatry, Mount Sinai School of Medicine, New York, N Y 10029, USA
Abstract
Cognitive impairments have been shown to predict impairments in adaptive functioning in patients with chronic schizophrenia and to be more predictive of overall outcome than positive or negative symptoms of the illness. Both adaptive and cognitive impairments are multidimensional, and it is possible that correlations between these domains may be limited to certain aspects of these functions. In this study, 208 geriatric patients with chronic schizophrenia were examined with a cognitive battery and assessed with a structured scale to determine the extent of their adaptive functions. Instrumental and social skills deficits were more strongly correlated with cognitive impairments than with the severity of undercontrolled behavior. Each of the cognitive measures was correlated with global social-adaptive deficits, with minimal variation in the magnitude of correlations. These results suggest that interventions should be individually targeted to cognitive-adaptive impairments and undercontrolled behavior. © 1997 Elsevier Science B.V. Keywords: Cognitive impairment; Skills deficit; Chronic schizophrenia
I. Introduction
Cognitive impairments are c o m m o n in schizophrenia (Gold and Harvey, 1993) and are more severe in patients with a more negative course of illness and chronic hospitalization (Davidson et al., 1995; Perlick et al., 1992). Similarly, deficits in adaptive functioning are c o m m o n in patients with a p o o r outcome (Keefe et al., 1987, 1996; Mueser et al., 1991 ), with the severity of deficits in adaptive functioning, and p o o r outcome previously reported being correlated with impairments in cognitive functioning (Breier et al., 1991; Harvey et al., * Corresponding author. Tel: 212-241-6637; fax: 212-860-3945; e-mail: 73414.2311@ compuserve.corn 0920-9964/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PH S0920-9964 (97) 00068-6
1997). Although positive symptoms of schizophrenia are severe in poor-outcome schizophrenic patients, the severity of these symptoms in verypoor-outcome patients has consistently been reported to be no greater than in patients with a less chronic course of illness (Keefe et al., 1987) and to be unrelated to the severity of cognitive impairments (Addington et al., 1991; Breier et al., 1991; Davidson et al., 1995). Additional aspects of schizophrenia other than cognitive and adaptive impairments contribute to extended hospital stays. In a recent study of over 800 geriatric psychiatric inpatients followed longitudinally during a period of downsizing, we found that elevations in belligerence and hostility, but not cognitive impairments, negative symptoms or
212
P.D, Harvey et al. /Schizophrenia Research 27 (1997) 21L-.218
psychotic symptoms, predicted failure of patients to be referred to alternative levels of care in the community (White et al., in press). Similar results were recently reported by Anderson and Trieman (1996), who found that behavioral disturbances, but not cognitive impairment, predicted referral to higher levels of care in geropsychiatric services. Even within the domain of adaptive deficits, there are multiple dimensions that could have differential prognostic importance and that possibly require differential interventions for successful treatment. For example, instrumental deficits might have a more adverse impact than social deficits in some types of community placements, and undercontrolled behavior might be manageable only in a secure ward at a psychiatric hospital. In the same vein, it is possible that various aspects of cognitive functioning could have a differential relationship with adaptive impairment. This possibility was explored in detail by Green (1996), who demonstrated that three types of cognitive impairment-vigilance deficits, memory impairments, and executive functioning deficits--were more strongly correlated than other aspects of cognitive functioning with poor response to attempts at remediation of adaptive deficits in schizophrenia. Thus, 'global' cognitive impairment was less important than specific cognitive impairments in the prediction of response to behavioral treatments. In this report, we present the results of a study examining differential relationships between cognitive and adaptive deficits in geriatric inpatients with chronic schizophrenia. These patients were evaluated for adaptive deficits with a structured rating instrument, the Social-Adaptive Functioning Evaluation (SAFE) scale (Harvey et al., 1997) and tested with a neuropsychological battery. The 17 individual items from the SAFE scale and the three factors derived during the development of the scale were correlated with a composite measure of cognitive impairment. Total adaptive deficit was correlated with each of the individual performance measures in the neuropsychological battery. A previous study has shown that SAFE scale total scores were significantly correlated with negative and cognitive symptoms of schizophrenia, but not with positive symptoms (Harvey et al., 1997). When the differential contri-
butions of global cognitive impairment and negative symptoms to SAFE scale total scores were examined by regression analysis, cognitive impairments were correlated with SAFE scale scores, but negative symptoms contributed no additional variance above that associated with the correlation between cognitive impairments and negative symptoms. Since some of those patients also participated in this study, those analyses were not repeated again here. The goal of this study was to determine the answers to the following questions: (1) Are there differences in the relationship of overall estimates of cognitive functioning and various aspects (e.g., social skills, instrumental skills, impulsive behavior) of adaptive functioning deficit in poor-outcome geriatric patients with schizophrenia? (2) Are various aspects of cognitive-neuropsychological functioning (e.g., memory, verbal skills) differentially related to overall adaptive deficits? (3) Can any individual measures of cognitive functioning adequately predict the level of adaptive deficit?
2. Methods
2.1. Subjects All patients were participants in a large-scale program of research on cognitive functioning and clinical symptoms in geriatric chronic psychiatric inpatients. Diagnostic assessments were performed by research staff members and a structured consensus procedure was employed in order to generate DSM-III-R diagnoses of schizophrenia. The entire assessment procedure for that study was published recently and all subjects in this study were diagnosed and assessed with that procedure (Davidson et al., 1995, 1996). Patients were excluded for the presence of any disorders that ruled out DSMIII-R schizophrenia, including mental retardation, substance dependence, neurological problems, and other psychiatric diagnoses. Subjects in this study consisted of all geriatric patients in the institution
P. D. Harvey et al. / Schizophrenia Research 27 (1997) 211 218
who met diagnostic criteria and could be evaluated with the neuropsychological battery. Forty-seven patients with Mini-Mental State Exam (MMSE) scores of 0 could not be tested with the entire cognitive battery and were excluded from participation in this study. A total of 254 geriatric schizophrenic patients provided complete cognitive assessment data. Of these patients, 36 were not completely assessable with the adaptive functioning ratings owing to limitations in physical ability or lack of opportunity to perform certain behaviors. Because this is a validity study, those patients were eliminated from the data analysis, leaving a total of 208 eligible subjects. Patients had a mean (_+_SD) age of 75.8+8.2 years (range, 65 96); 44% of subjects were male. All had been hospitalized for at least 10 consecutive years (range, 11-58) and none had an onset age later than 45 years or earlier than 16years. Patients had completed 9.7+3.17 years of formal education (range, 6 14). The average age at first psychiatric hospitalization was 30.7+ 13.7 years (range, 16 45).
2.2. Cognitive assessment All subjects were examined with a variety of clinical and cognitive assessments. Patients were examined with the MMSE (Folstein et al., 1975) and the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Cognitive Battery (Morris et al., 1989). This battery, described previously by Welsh et al. (1992), examines a variety of functions affected by Alzheimer's Disease and other progressive dementing conditions. We have previously demonstrated the reliability and validity of this battery in assessing patients with chronic schizophrenia (Davidson et al., 1996; Harvey et al., 1996).
2.3. CERAD battery 2.3.1. Word list learning and delayed recall A 10-item list of words is presented to the subject on three separate learning trials. After each trial, free recall of the list is required of the subject. After a delay, filled by the Praxis Examination
2I 3
described below, recall of the word list is required. Dependent variables for this report were the number of words recalled on the first learning trial, the total number of words recalled over three learning trials, and the proportion of words learned by trial three that were recalled at the delayed recall (savings).
2.3.2. Praxic drawings Four drawings (circle, diamond, overlapping rectangles, and cube) are presented to the subject, who is instructed to copy them exactly. Reproductions are scored according to predetermined criteria. The dependent variable is the total score for all four drawings. 2.3.3. Modified Boston Naming Test Subjects are presented with 15 line drawings and asked to name the object depicted. Of the 15 drawings, five are of objects with high frequency of occurrence in spoken English, five of moderate frequency, and five of low frequency. The dependent variable is the total number of correct namings. 2.3.4. Category fluency Subjects were asked to name as many animals as they could in a 1-min period. The dependent variable is the number of unique animals named. 2.4. Adaptive functioning All patients were rated with the Social-Adaptive Functioning Evaluation (SAFE) scale (Harvey et ai., 1997) by trained raters from the research team (the SAFE scale is available from the authors). These raters were different from those performing the cognitive assessment. The SAFE scale is a structured 17-item scale designed to assess multiple aspects of adaptive functioning in geriatric inpatients. Ratings are generated for the patients' behavior 'on average' for the past month on a 5-point (0-4) scale, based on the raters' condensation of observation of a patient reading of the chart and a caregiver report. Adaptive deficits are given a score of 0 if there is no impairment, and 4 if there is severe and incapacitating impairment. For example, for item 11, instrumental social skills, mild
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impairment (severity of 1.0) is defined as follows: "The patient is often able to achieve the instrumental goals of his interactions. The patient may occasionally ask an inappropriate person for something. Social skill problems may occasionally limit the patient's ability to achieve instrumental goals (e.g., the patient demands something rather than requests it, he stands inappropriately close to the other person, he speaks in a low voice tone)." Whereas severe impairment (3.0) is defined as follows: "The patient rarely attains instrumental goals of social interactions, because of poor social skills and misperception of social roles. The patient approaches others occasionally to achieve instrumental goals." Patients who had no opportunity to perform behaviors in a skills domain (e.g., no relatives called on the telephone; restricted to ward and not permitted to move around the hospital grounds) were not rated on that item and were excluded from the analyses. At the time of the assessment, raters were unaware of the results of the cognitive assessment of the patients. Interrater reliability, that is, intraclass correlations of the ratings for the individual items of the scale, based on 50 patients, ranged from a low of 0.87 to 0.98 (all p <0.001) and 1-week test-retest reliability ranged from 0.59 to 0.86. Total score intraclass correlations were 0.99 for both interrater and test-retest reliability. Factor analyses during the development of the scale revealed three factors, labeled 'Instrumental and self-care'; 'Impulsivity'; and 'Social functions'. The dependent variables for this study, depending on the analysis, were the item, total, or factor scores.
2.5. Data analyses Although there was a reasonably large overall population in the study, analyses were performed as conservatively as possible in order to reduce the overall number of correlations computed. Total scores on the SAFE scale were used for correlation with individual cognitive functioning dependent variables, in order to reduce the number of correlations computed. Similarly, a composite index of cognitive impairment was created for use in the correlational analyses examining the individual SAFE items and the SAFE factor scores.
2.5.1. Creation of a composite measure of cognitive impairment Total Boston Naming Test scores, total Praxis test scores, Word List Trial 1 scores, Word List Total Learning scores (Trials 1-3), Word List Savings scores (Delayed Recall/Trial 3), and Category Fluency scores were all standardized by creating z-scores on the basis of the performance of the entire sample of patients. A single composite was created by averaging these individual z-scores (the correlations between the individual cognitive dependent variables were all greater than Pearson r=0.60). M M S E scores were not entered into the composite measure because of the redundancy created by including a global functioning scale with individual neuropsychological tests. 2.5.2. Correlational analysis The 17 individual SAFE items were correlated with the composite measure of cognitive functioning described above with Pearson correlations. Similarly, SAFE factor scores and total scores were also correlated with the composite cognitive functioning measure. The individual cognitive functioning measures were correlated with total SAFE scores with Pearson correlations. 2.5.3. Regression analyses After the correlational analyses, stepwise regression analyses were computed in order to identify the best predictors of the criterion variables of interest. In the case of the relationship between SAFE scale scores and composite cognitive impairments, the variables used to predict the cognitive composite were the three SAFE factor scores. For the prediction of SAFE total scores, the predictors were the six individual cognitive functioning measures.
3. Results
Table 1 presents the scores on the SAFE scale and the correlation between individual SAFE scale items, factor scores, and total scores, and the composite measure of cognitive functioning. Although all correlations were statistically significant (all p values <0.006, uncorrected), two of
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Table 1 Mean (_+SD) scores on the Social-Adaptive Functioning Evaluation scale (SAFE) and correlations of the SAFE scores with global cognitive functioning Score
Pearson r a
Factor SC SC SC SC SC SC IC IC SF SF SF SF SF SF SF SF IC
Bathing and grooming Clothing and dressing Eating, feeding and diet Money management Neatness and maintenance Orientation and mobility Impulse control Respect for property Communication skills Conversational skills Instrumental social skills Social appropriateness Social engagement Friendships Recreation and leisure Participation in hospital activities Cooperation with treatment
2.02 ± 1.17 1.87 + 1.09 1.46 _+0.95 2.97 + 1.50 3.32 _+ 1.25 3.13 ± 1.12 1.19 ± 1.23 1.36 + 1.34 3.36+ 1.22 2.26 ± 1.26 1.59 _+ 1.40 1.57 ± 1.04 2.59+_0.99 2.97 ± 1.11 2.45 ± 1.09 2.28 + 1.10 1.59 _+0.79
- 0.578 - 0.521 - 0.526 - 0.586 - 0.383 - 0.498 - 0.189 - 0.413 -0.517 - 0.684 -0.657 -0.435 -0.48l - 0.451 - 0.488 - 0.405 - 0.202
Factor 1 (Instrumental and self-care) Factor 2 (Impulse control ) Factor 3 (Social functions)
2.63 +0.91 1.57 +_0.83 2.23 _+0.89
-0.688 --0.372 -0.667
39.08 ± 13.24
-0.719
SAFE total score
SC =Self care; SF =Social functions; IC = Impulse control. aAll p values _<0.006.
the SAFE scale items were notably less strongly correlated with cognitive functioning than the other items: impulse control and cooperation with treatment. These items are most strongly loaded on the impulse control factor, which was also considerably less strongly correlated with cognitive functioning than the other two factors, z tests of the significance of the difference between correlations found that the larger of these two correlations, 'cooperation with treatment', was significantly smaller than the next smallest correlation ('neatness and maintenance') at p<0.01. Similarly, the correlation between the impulse control factor score and the composite measure of cognitive impairment was also significantly (p<0.001) smaller than the correlation between the social functions factor and the cognitive impairment composite score. In the stepwise regression analysis, the overall analysis was significant, R2=0.53, F(2 205)= 116.51, p<0.001.
Both 'Instrumental and self-care' and 'Social functions' accounted for significant variance increments in the cognitive composite score, while 'Impulse control' did not enter the regression analysis. These findings indicate that cognitive impairments are more strongly correlated with skills deficits, both social and instrumental, than with behavioral undercontrol in these subjects. Table 2 presents the scores on the cognitive neuropsychological measures and their correlation with total SAFE scale scores. Of all the individual cognitive items, the smallest correlation (delayed recall savings) with adaptive deficits still accounted for over 22% variance in SAFE scale total scores and was significant at p<0.001. Overall cognitive composite scores and MMSE scores were very strongly correlated with SAFE scale total scores. In the stepwise regression analysis, the overall analysis was statistically significant, F(4,203) = 44.90, p<0.001, R2=0.53. Of the six individual
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Table 2 Mean (± SD) scores on tests of cognitive functioning and correlations with Social-Adaptive Functioning Evaluation scale (SAFE) total scores
Boston Naming Test Constructional praxis Word List Learning Trial One Word List Total Learning Word List Savings Verbal Fluency Test total M M S E total Cognitive composite score
Score
Pearson r a
7.59+_5.18 3.88 _+3.45 1.52 + 1.83 6.80_+6.66 0.26_+0,41 10.89 _+ 13.00 14.64_+9,06
-0.577 - 0.623 -0.540 -0.640 -0.470 - 0.648 -0.729 -0.719
aAll p values _<0.00l.
cognitive items, only Boston Naming total scores and Word List Learning Delayed Recall Savings scores did not enter the regression on a significant basis. Thus, these results indicate that there is no individual cognitive test that predicts the level of adaptive deficit considerably better than the others, and that composite measures of cognitive dysfunction are highly associated with the overall level of social and adaptive deficit seen.
4. Discussion
Adaptive deficits in poor outcome geriatric patients with schizophrenia are multidimensional, as evidenced by their differential patterns of correlation with cognitive impairments. Impulsivity is less strongly associated with cognitive impairments than social and instrumental skills deficits, whereas in the domain of cognitive impairments, nearly all aspects of functioning measured in the study contributed independent variance to deficits in adaptive skills. These results suggest that social and adaptive skills deficits in geriatric chronic schizophrenic patients are independently related to deficits in learning, verbal skills, and praxic functions, with no single aspect of cognitive impairment being a much better predictor of the level of global adaptive deficit. Before proceeding to the implications of these findings, a review of the limitations of the study is important. These are very-bad-outcome patients
who are not typical of all geriatric patients with schizophrenia. It is well known that better-outcome geriatric patients with schizophrenia have markedly reduced cognitive impairments (Heaton et al., 1994). Impulse control deficits were markedly reduced in their level of severity compared to adaptive functioning deficits, which could have affected correlations with variables from other domains. This is a brief cognitive assessment oriented at dementia and does not include some of the typical tests found to correlate with adaptive deficit in younger patients (e.g., vigilance and the Wisconsin Card Sorting Test). Inclusion of these tests might strengthen the present pattern of results, or it might even increase the correlation between impulsivity and cognitive impairment. All of the cognitive measures were quite highly correlated with each other, limiting the ability of the analyses to find differential correlations between individual cognitive measures and adaptive functioning deficit. Finally, the impulsivity factor has the fewest items; consequently, it might simply be less strongly correlated with adaptive deficits, because it is less reliable. There are two main implications of these findings. Even in patients at the far end of the distribution of cognitive impairment and adaptive deficit, there are powerful relationships between these two aspects of schizophrenia. These findings underscore the likely merit of cognitive enhancement on adaptive functioning, even in patients who are seriously impaired. Since behavioral cognitive rehabilitation approaches are presently of doubtful merit (Bellack, 1992; Green, 1993), pharmacological interventions seem to be the most promising area for intervention. Whereas typical neuroleptic medication has had very poor results for improving the critical cognitive impairments in schizophrenia (Medalia et al., 1988), other than certain attentional functions (Serper et al., 1994), some recent positive results involving amphetamine (Goldberg et al., 1991), clozapine (Lee et al., 1994) and risperidone (Gallhofer et al., 1996) all suggest that these agents may have promise for the future. Systematic trials of the effects of these medications and augmentation strategies, including patients at all levels of severity, are clearly called for.
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The second implication is that there are two generally independent aspects of social-instrumental deficits in geriatric schizophrenic patients with a poor course of illness: adaptive deficits and behavioral undercontrol. These findings are consistent with earlier research findings that aggressivity extends acute admission for psychogeriatric patients (Mulsant et al., 1993) and that impulsive behavioral undercontrol on the part of chronic geropsychiatric inpatients was a much stronger predictor of being hard to place (Anderson and Trieman~ 1996; White et al., in press) than cognitive or adaptive impairments. Since cognitive impairments were found to be relatively weakly related to the severity of impulsive behaviors, it is unlikely that a single treatment strategy would be effective for both of these dimensions of schizophrenia. These findings suggest that pharmacologic interventions for geriatric inpatients require two independent, and possibly competing, goals. Many current interventions that are used in clinical settings to reduce belligerence (e.g,, benzodiazepines or low-potency neuroleptics with anticholinergic effects) have the potential to adversely affect cognitive functioning and, possibly, social and adaptive skills. Thus aggressive pharmacologic treatment of undercontrolled behavior appears to have the potential to exacerbate cognitive impairments and skills deficits. Behavioral interventions may have more promise in this area. Prioritizing these competing needs is a clinical goal that seems critical for reducing the incidence of adverse outcomes in psychogeriatric patients. Future research in pharmacologic treatment of schizophrenia should adopt a biphasic approach toward outcome in order to measure the success of interventions on these two domains of functioning. An additional useful direction would be the application of controlled clinical trials designed to examine combined pharmacological and behavioral intervention strategies, in order to optimize outcome across these two domains.
Acknowledgment This research was supported by grant number MH46436 awarded to Dr. Davidson. The authors
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thank the following staff members who contributed to this study: Janice McCrystal, Stephanie Bowler, Rita Ohsiek, Susan Frick and Cynthia Blum.
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