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Convergence of cognitive and adaptive decline in late-life schizophrenia
Schizophrenia Research 35 (1999) 77–84
Convergence of cognitive and adaptive decline in late-life schizophrenia Philip D. Harvey *, Michael Parrella, Leonard White, Richard C. Mohs, Michael Davidson, Kenneth L. Davis Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY 10029, USA Received 10 November 1997; accepted 17 August 1998
Abstract Cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia. Despite the significant impairments seen on the part of many patients with schizophrenia that implicate decline at some point in time, there have been no longitudinal studies of adaptive decline in patients with schizophrenia. In this study, 57 geriatric patients with chronic schizophrenia were examined with measures of clinical symptoms, cognitive impairments, and adaptive functioning while living in a chronic psychiatric hospital and followed up an average of two and a half years after their referral to nursing home care. Cognitive functioning and adaptive functioning both declined over the follow-up period, whereas there was no change in schizophrenic symptoms. Changes in cognitive functioning accounted for 25% of the variance in adaptive decline, whereas the baseline severity of cognitive impairment and schizophrenia symptoms were uncorrelated with adaptive decline. These data indicate that cognitive decline may predict deterioration in overall functional status and imply that treatment of cognitive impairment might have a beneficial effect on global functional status. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Cognitive decline; Adaptive decline; Late-life schizophrenia
1. Introduction Cognitive deficits appear to be a major predictor of adaptive dysfunction in schizophrenia and other neuropsychiatric conditions ( Heaton and Pendleton, 1981). Across many different studies, those patients with schizophrenia whose cognitive impairments were more severe have been found to be more adaptively impaired on a cross-sectional basis (Serban and Gidynski, 1979; Perlick et al., 1992; Harvey et al., 1998). In addition, more severe * Corresponding author. Tel: +1 212 824 7140; Fax: +1 212 860 3945; e-mail: [email protected]
cognitive impairments at baseline predict greater functional deficit at various follow-up periods (e.g. Breier et al., 1991). Many studies [reviewed by Green (1996)] have also demonstrated that specific types of cognitive deficits predict failure on the part of patients with schizophrenia to benefit from interventions aimed at enhancement of adaptive skills. Finally, there appears to be a pattern of specific relationships between subcomponents of adaptive dysfunction and cognitive impairment ( Harvey et al., 1997c). Specifically, both social and instrumental deficits are associated with cognitive impairment, whereas impaired impulse control is much less strongly correlated with cognitive impairments.
0920-9964/99/$ – see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 2 0 -9 9 6 4 ( 9 8 ) 0 0 10 9 - 1
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
Although some geriatric patients with schizophrenia appear to have an adequate functional outcome in late life (Harding et al., 1987), many patients have severe adaptive deficits ( Kincaid et al., 1995; Harvey et al., 1997a), even when living in the community (Bartels et al., 1997). These deficits are more severe in patients with a more chronic course of illness (Harvey et al., 1998) and can be detected with examiner ratings (Harvey et al., 1997a), caregiver reports ( Kincaid et al., 1995), and direct functional assessment ( Klapow et al., 1997). Cognitive impairments have been found to be correlated cross-sectionally with adaptive deficits that were measured with all three of these assessment methods. Thus, even in the severely impaired end of the adaptive functioning spectrum in schizophrenia, impairment in cognitive functioning predicts adaptive deficit. Whereas longitudinal studies have shown that cognitive deficits predict failures in the behavioral treatment of adaptive deficits, most studies of the correlation between cognitive and adaptive deficits have been cross-sectional. Since the profound cognitive impairments seen in some poor-outcome geriatric patients (Arnold et al., 1995; Davidson et al., 1995, 1996) with schizophrenia implicate deterioration at some point in time after the onset of the illness, the consistent correlational relationship between cognitive and adaptive deficit would suggest that adaptive functioning should also be found to decline. In support of this idea, previous research on adaptive deficit in geriatric poor-outcome patients has found older patients to be more impaired (Harvey et al., 1997a), although this could be related to normal aging-related declines in adaptive skill. The current report presents preliminary data from a longitudinal study of the correlation between changes in adaptive functioning and changes in cognitive functioning. A sample of geriatric patients with schizophrenia received a clinical assessment while hospitalized in a longstay psychiatric hospital and were then seen again after their discharge from the hospital and referral to a nursing home. All of the patients were examined with ratings of positive and negative schizophrenia symptoms, adaptive functions, and cognitive impairments, and the correlations
between these variables at baseline and over time were calculated. Our hypotheses were that: (1) declines in cognitive functioning would predict declines in adaptive skill, and (2) changes in cognitive functioning would be more strongly correlated than any other variables with changes in adaptive functioning.
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-IIIR diagnoses of schizophrenia. The entire assessment procedure for that study has been published, and all subjects in this study were diagnosed and assessed with that procedure (Davidson et al., 1995, 1996). Patients had previously been excluded at prior assessments for the presence of any disorders that ruled out DSMIIIR schizophrenia, including mental retardation, substance dependence, neurological diseases or damage, and other psychiatric diagnoses. All patients who had been uncooperative with testing or who had a Mini-Mental Sate Examination (MMSE; Folstein et al., 1975) score of 0 had been excluded at the initial or follow-up assessments. The subjects in this particular component of the study had been diagnosed and assessed while in chronic psychiatric care and then had been discharged from the hospital to a nursing home. All of these patients were participants in the initial Davidson et al. (1995) paper. These patients are not included in the sample of nursing home patients with schizophrenia reported by Harvey et al. (1998) since those patients were all recruited and assessed for the first time in nursing home care. Patients were re-evaluated at the nursing home where they were in residence for 1–5 years after their discharge (mean=2.6 years). All of the subjects in this study had been hospitalized for at least 10 consecutive years before their discharge to
79
P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
the nursing home (range=11–58), and none of the patients in this study had an onset age for schizophrenic symptoms of later than 45 or earlier than 16. All patients were receiving typical neuroleptic medication at their initial assessment, and three patients had been changed to risperidone by the time of the reassessment. These three patients were excluded from the current analysis because of previous findings suggesting that risperidone treatment may enhance cognitive functioning in late-life schizophrenia (Berman et al., 1996). As a result, there were 57 patients with full assessment data. Table 1 presents demographic information on the patients. This information includes medication status, including antipsychotic medications, anticholinergic medications, sedatives, and medication for physical illness, at each of the two assessments of the patients. Consistent with our previous research (Harvey et al., 1997b; White et al., 1997),
we also collected and presented information on treatment of several different physical illnesses, including cardiac problems (hypertension and ischemic problems), diabetes, and pulmonary conditions. 2.2. Cognitive and clinical assessment All subjects were examined in the hospital with a variety of clinical and cognitive assessments, of which the current battery is a subset. Patients were examined with the Mini-Mental State Examination (MMSE; Folstein et al., 1975). This instrument is a 30-point scale that assesses a variety of cognitive functions, including orientation, registration, concentration, delayed recall, and verbal skills. Our previous research found an inter-rater reliability (intraclass correlation; ICC ) of 0.99 in this population. Schizophrenia symptoms were examined with
Table 1 Descriptive information on patients at both assessments Gender distribution (percentage male)
44
Racial ethnic distributions Caucasian African-American Hispanic
84 11 5
Age at baseline Age at first psychiatric admission Years of education completed
9.7
Mean
SD
77.8 30.7 3.2
8.2 13.7
Baseline Medications and dosages Antipsychotic (Chlorpromazine equivalent) Anticholinergic (Benztropine dose) Benzodiazipines Anticonvulsants Treatment for physical illnesses Cardiac Pulmonary Diabetes
Percentage receiving 100 9
Follow-up Mean
SD
60.4
10.6
1.0
14 5
—
Percentage receiving 95 5
Mean
SD
64.4
11.8
1.0
2 5 Baseline (percentage receiving) 21 5 4
No patients received treatment with lithium or SSRI antidepressants at either assessment.
Follow-up (percentage receiving) 28 4 4
—
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
the Positive and Negative Syndrome Scale (PANSS; Kay, 1991). The PANSS contains 30 items, with seven items rating positive symptoms, seven rating negative symptoms, and 16 other items assessing ‘general psychopathology’. The rating procedures and reliability of the assessments in schizophrenic patients have been described previously (Davidson et al., 1995). For the purposes of this study, we examined the total scores on the Positive and Negative Subscales as the dependent variables. 2.3. Adaptive functioning All patients were rated with the Social-Adaptive Functioning Evaluation (SAFE; Harvey et al., 1997a) scale by trained raters from the research team. 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 five-point (0–4) scale, on the basis of the raters’ condensation of their observation of the patient, reading of the chart, and caregiver report. Raters interviewed a member of the treatment team at both the nursing home and the psychiatric hospital in order to obtain the caregiver report. Adaptive deficits receive a score of 0 if there is no impairment and 4 if there is severe and incapacitating impairment. According to the instructions for the SAFE scale, patients who had no opportunity to perform behaviors in a skills domain (e.g. no relatives to call on the telephone; restricted to ward and not permitted to move around the hospital grounds) are not rated on that item. None of the patients in the current sample were in such a situation. At the time of the reassessment, raters were unaware of the results of the previous evaluations of the patients. The interrater reliability ( ICC ) of the ratings for the individual items of the scale, based on 50 patients, ranged from a low of 0.87 to a low of 0.98 (all p<0.001) and 1 week test–retest reliability (ICC ) ranged from 0.59 to 0.86. Total score ICCs were 0.99 for both interrater and test–retest reliability. The dependent variable for this study was the total score, reflecting adaptive functioning across all 17 items.
3. Results Table 1 presents information on subjective descriptive characteristics, including medication treatment. As can be seen in the table, the patterns of medical illness and treatment with psychotropic and anticholinergic medication were essentially identical at each of the two assessments of the patients. The only patients who received new medications at the nursing home were three patients who received new treatment with cardiac medications. In addition, fewer patients received benzodiazipine medications at the nursing home than at the state psychiatric hospital. Table 2 presents the scores for the PANSS subscales, the MMSE, and the SAFE scale total scores at the baseline and follow-up assessments. T-tests were used to test for change in the symptoms over time. As shown in the table, a significant degree of worsening in both MMSE scores and in SAFE scale total scores was found over the follow-up period. For both positive and negative subscales, there was no significant change over the follow-up period. In order to perform the correlational analyses, change scores from baseline to follow-up were calculated. Pearson product-moment correlations were calculated between SAFE scale change scores and baseline and change scores on PANSS positive, PANSS negative symptoms subscales and the MMSE, as well as with baseline scores on the SAFE scale. These correlations are presented in Table 3. As can be seen in Table 3, there were only two statistically significant predictors of SAFE scale change scores: baseline levels of adaptive functioning deficits and MMSE change scores. In order to determine whether any of the other variables accounted for variance in SAFE scale change scores, a forward entry stepwise regression was computed. All variables in Table 2 were entered into the equation. The overall regression was significant [F(2,54)=10.26, p<0.001]. Only two variables entered the equation, change in MMSE scores, accounting for 34% of the variance, followed by baseline scores on the SAFE scale, accounting for 16% of the variance. Thus, when the influence of other variables is controlled, the
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84 Table 2 Clinical symptoms, cognitive impairments, and adaptive deficits over the follow-up period Baseline
Positive and Negative Syndrome Scale Positive Negative Mini-mental State Examination Social and Adaptive Functioning Evaluation Total Score
Table 3 Correlations between baseline and change scores on assessment measures Changes in SAFE Scale scores Baseline scores PANSS positive PANSS negative MMSE SAFE Scale Change scores PANSS positive PANSS negative MMSE
0.18 0.07 −0.03 0.41* 0.19 0.17 −0.49**
*p<0.01. **p<0.001.
importance of changes in MMSE for the prediction of SAFE scale scores appears even more salient. The correlations between several other variables and SAFE scale change scores were calculated, in order to determine whether there were any other factors that were associated with changes in adaptive functioning. The length of the follow-up interval, r=0.12, baseline age, r=0.10, age at follow-up, r=0.12, age at first psychiatric admission, r=−0.03, and dose of antipsychotic medication at follow-up, r=0.04 were all uncorrelated with decline in adaptive functioning as measured by the SAFE scale.
4. Discussion Moderate levels of cognitive and adaptive decline are found in geriatric patients with schizophrenia over an average of approximately 2.5 years
Follow-up
Mean
SD
Mean
SD
t
p
18.23 32.21 9.76 45.62
5.56 9.06 7.32 11.01
18.11 32.05 5.94 50.00
5.52 7.12 7.91 11.15
0.18 0.16 4.77 2.81
ns ns 0.001 0.05
after referral to nursing home care. These declines are intercorrelated and are not associated with the baseline severity of positive or negative symptoms. Since positive and negative schizophrenia symptoms did not worsen for the group as a whole over the follow-up period, there was no realistic possibility of their predicting declines in adaptive functioning. The declines in adaptive functioning are not associated with the length of the follow-up interval and are not simply due to aging. The level of cognitive and adaptive decline seen is less than expected in a similar follow-up period in patients with Alzheimer’s Disease (AD). According to previous research (e.g. Morris et al., 1993), patients with AD would be expected to decline by as much as six MMSE points in a similar time period, a rate of decline that is three times as great as that seen in our patients with schizophrenia. In addition, these changes in adaptive status do not appear to be related to changes in treatment for psychiatric symptoms or physical illness status. There are some limitations of this study. All patients were chronic patients with a very poor outcome who had severe cognitive impairments at baseline. Previous studies of better outcome patients found much higher MMSE scores in their patients ( Klapow et al., 1997) and limited evidence of age effects on cognitive functioning (Heaton et al., 1994; Palmer et al., 1997). The researchers who performed those studies found significant correlations between MMSE scores and adaptive functioning deficit, however ( Klapow et al., 1997). Since the magnitude of change in MMSE scores on average is inconsistent with that seen in degenerative dementia due to Alzheimer’s Disease and the prevalence of AD at postmortem has been
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
reported to be only 10% in schizophrenic patients from this same sample with severe cognitive impairments (Powchik et al., 1998; Purohit et al., 1998), it seems necessary to conclude that some degenerative process associated with chronic schizophrenia is responsible for the observed change in cognitive and adaptive functioning. There are several possible mechanisms that might cause the changes in cognitive and adaptive functioning seen. A stepwise pattern of decline in cognitive and functional status in some very poor outcome geriatric schizophrenic patients has previously been reported in the patients from our sample who were not discharged from the psychiatric hospital to nursing care (Harvey et al., in press). In that study, it was found that approximately 30% of patients appeared to manifest discrete periods of cognitive decline that did not occur progressively across several consecutive years. In progressive dementing conditions such as AD, adaptive skills have been shown to decline concurrently to or slightly after changes in cognitive functioning, with the results of this study indicating that this same process may occur in some elderly patients with very poor outcome schizophrenia (Mortimer et al., 1992; Green et al., 1993). The finding of deterioration in cognitive and functional status in poor outcome patients is consistent with very recent reports of progressive increases in cortical ventricular size in childhood onset (Rapoport et al., 1997), first episode (Delisi et al., 1997), and chronic (Davis et al., 1998) schizophrenia over relatively brief follow-up periods. The mechanism of brain changes and cognitive decline is not clear, although it has been suggested that extended periods of symptomatic exacerbation may cause neurodegeneration through glutamate excito-toxicity (Olney and Farber, 1995). This model would suggest that periods of exacerbation would precede cognitive decline, which would then lead to increased impairments in adaptive functioning. An additional possibility is that somehow these declines in cognitive and functional status are associated with the process of deinstitutionalization and referral to alternative residential care. This explanation is rendered somewhat implausible because of the lack of change in
positive and negative symptoms. Similarly, previous research in the UK has found that some longstay patients’ symptoms improve after discharge from long-term psychiatric care (Leff et al., 1994). If a process of global psychological reaction to environmental events was responsible for the current cognitive decline, then it is difficult to explain why both positive and negative symptoms would be unaffected. The SAFE scale is designed for use in institutional settings such as nursing home care, so declines caused by psychometric artifacts are unlikely. The issue of environmental versus biological mechanisms of cognitive decline cannot, however, be resolved by the current study. Later research, in addition to focusing on the causes of this correlated cognitive and adaptive decline, should examine the reversibility of adaptive decline. Since several recent studies have indicated that cognitive deficits may be improved by treatment with atypical neuroleptic medications (e.g. Berman et al., 1996; Green et al., 1997), longitudinal research should examine the consequences of such treatment on adaptive functioning deficit. These studies should include studies of the facilitation of rehabilitation treatments through reversal of cognitive barriers to treatment. Also important is the possibility of spontaneous reversal of adaptive deficits by improvement of cognitive impairments. It may be that the performance of previously acquired adaptive skills is impaired by cognitive dysfunction, with these skills being performed more adequately after the reversal of cognitive impairment through pharmacological treatment.
Acknowledgments This research was supported by grant number MH46436 awarded to Dr Davidson and by the assessment core (P.D. Harvey, PI ) of the Mt. Sinai Mental Health Clinical Research Center ( K.L. Davis, PI ). The authors would like to thank the following staff members who contributed to this study: Janice McCrystal, Stephanie Bowler, Rita Ohsiek, Susan Frick, and Cynthia Blum.
P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
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Schizophrenic Patients: A Cross-Sectional Study Across 9 Decades. Am. J. Psychiatry 154, 205–210. Harvey, P.D., Sukhodolsky, D., Parrella, M. et al., 1997c. The association between cognitive and adaptive deficits in geriatric chronic schizophrenic patients. Schizophr. Res. 27, 211–218. Harvey, P.D., Howanitz, E., Parrella, M. et al., 1998. Cognitive, adaptive, and symptomatic features of schizophrenia in late life: a comparison of nursing home, chronically hospitalized and acutely admitted patients. Am. J. Psychiatry 155, 1080–1086. Harvey, P.D., Silverman, J., Mohs, R.C. et al., in press. Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients. Biol. Psychiatry. Heaton, R., Paulsen, J.S., McAdams, L.A. et al., 1994. Neuropsychological deficits in schizophrenics: Relationship to age, chronicity, and dementia. Arch. Gen. Psychiatry 55, 469–476. Heaton, R.K., Pendleton, M.G., 1981. Use of neuropsychological tests to predict patients everyday functioning. J. Con. Consult. Psychol. 49, 807–821. Kay, S.R., 1991. Positive and Negative Syndromes in Schizophrenia. Brunner/Mazel, New York. Kincaid, M.M., Harvey, P.D., Parrella, M. et al., 1995. Validity and utility of the Alzheimer’s Disease Assessment Scale-Late Version (ADAS-L) for the measurement of cognitive and functional impairment in geriatric chronic schizophrenic in patients. J. Neuropsychiatry Clin. Neurosci. 7, 6–81. Klapow, J., Evans, J., Patterson, T.L. et al., 1997. Direct assessment of functional status in older patients with schizophrenia. Am. J. Psychiatry 154, 1022–1024. Leff, J.P., Thornicroft, G., Coxhead, N. et al., 1994. The TAPS Project. 22: A five-year followup of long stay psychiatric patients discharged to the community. Br. J. Psychiatry 165 (Suppl. 25), 13–17. Morris, J.C., Edland, S., Clark, C. et al., 1993. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer’s disease. Neurology 43, 2457–2465. Mortimer, J.A., Ebbitt, B., Jun, A.P., 1992. Predictors of cognitive and functional progression in patients with probable Alzheimer’s disease. Neurology 42, 1689–1696. Olney, J.W., Farber, N.B., 1995. Glutamate receptor dysfunction and schizophrenia. Arch. Gen. Psychiatry 52, 998–1007. Palmer, B.W., Heaton, R.K., Paulsen, J.S. et al., 1997. Is it possible to be schizophrenic and neuropsychologically normal? Neuropsychology 11, 437–447. Perlick, D., Stastny, P., Mattis, S. et al., 1992. Contribution of family, cognitive, and clinical dimensions to long-term outcome in schizophrenia. Schizophr. Res. 6, 257–265. Powchik, P., Haroutunian, V., Davidson, M. et al., 1998. Postmortem studies in schizophrenia with specific reference to cognitive impairment. Schizophr. Bull. 24, 325–342. Purohit, D.P., Perl, D., Haroutunian, V. et al., 1998. Alzheimer’s disease and related neurodegenerative diseases in
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elderly schizophrenic patients: A postmortem neuropathologic study of 100 cases. Arch. Gen. Psychiatry 55, 205–211. Rapoport, J.L., Giedd, J., Kumra, S. et al., 1997. Childhood onset schizophrenia: Progressive ventricular change during adolescence. Arch. Gen. Psychiatry 54, 897–903. Serban, G., Gidynski, C.B., 1979. Relationship between cogni-
tive defect, affect response, and community adjustment in chronic schizophrenics. Br. J. Psychiatry 134, 602–608. White, L., Parrella, M., McCrystal-Simon, J. et al., 1997. Characteristics of elderly psychiatric patients retained in a state hospital during downsizing: A prospective study with replication. Int. J. Geriatr. Psychiatry 12, 474–480.
Convergence of cognitive and adaptive decline in late-life schizophrenia Philip D. Harvey *, Michael Parrella, Leonard White, Richard C. Mohs, Michael Davidson, Kenneth L. Davis Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY 10029, USA Received 10 November 1997; accepted 17 August 1998
Abstract Cognitive impairment has proven to be a major predictor of overall functional deficit in schizophrenia. Despite the significant impairments seen on the part of many patients with schizophrenia that implicate decline at some point in time, there have been no longitudinal studies of adaptive decline in patients with schizophrenia. In this study, 57 geriatric patients with chronic schizophrenia were examined with measures of clinical symptoms, cognitive impairments, and adaptive functioning while living in a chronic psychiatric hospital and followed up an average of two and a half years after their referral to nursing home care. Cognitive functioning and adaptive functioning both declined over the follow-up period, whereas there was no change in schizophrenic symptoms. Changes in cognitive functioning accounted for 25% of the variance in adaptive decline, whereas the baseline severity of cognitive impairment and schizophrenia symptoms were uncorrelated with adaptive decline. These data indicate that cognitive decline may predict deterioration in overall functional status and imply that treatment of cognitive impairment might have a beneficial effect on global functional status. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Cognitive decline; Adaptive decline; Late-life schizophrenia
1. Introduction Cognitive deficits appear to be a major predictor of adaptive dysfunction in schizophrenia and other neuropsychiatric conditions ( Heaton and Pendleton, 1981). Across many different studies, those patients with schizophrenia whose cognitive impairments were more severe have been found to be more adaptively impaired on a cross-sectional basis (Serban and Gidynski, 1979; Perlick et al., 1992; Harvey et al., 1998). In addition, more severe * Corresponding author. Tel: +1 212 824 7140; Fax: +1 212 860 3945; e-mail: [email protected]
cognitive impairments at baseline predict greater functional deficit at various follow-up periods (e.g. Breier et al., 1991). Many studies [reviewed by Green (1996)] have also demonstrated that specific types of cognitive deficits predict failure on the part of patients with schizophrenia to benefit from interventions aimed at enhancement of adaptive skills. Finally, there appears to be a pattern of specific relationships between subcomponents of adaptive dysfunction and cognitive impairment ( Harvey et al., 1997c). Specifically, both social and instrumental deficits are associated with cognitive impairment, whereas impaired impulse control is much less strongly correlated with cognitive impairments.
0920-9964/99/$ – see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 2 0 -9 9 6 4 ( 9 8 ) 0 0 10 9 - 1
78
P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
Although some geriatric patients with schizophrenia appear to have an adequate functional outcome in late life (Harding et al., 1987), many patients have severe adaptive deficits ( Kincaid et al., 1995; Harvey et al., 1997a), even when living in the community (Bartels et al., 1997). These deficits are more severe in patients with a more chronic course of illness (Harvey et al., 1998) and can be detected with examiner ratings (Harvey et al., 1997a), caregiver reports ( Kincaid et al., 1995), and direct functional assessment ( Klapow et al., 1997). Cognitive impairments have been found to be correlated cross-sectionally with adaptive deficits that were measured with all three of these assessment methods. Thus, even in the severely impaired end of the adaptive functioning spectrum in schizophrenia, impairment in cognitive functioning predicts adaptive deficit. Whereas longitudinal studies have shown that cognitive deficits predict failures in the behavioral treatment of adaptive deficits, most studies of the correlation between cognitive and adaptive deficits have been cross-sectional. Since the profound cognitive impairments seen in some poor-outcome geriatric patients (Arnold et al., 1995; Davidson et al., 1995, 1996) with schizophrenia implicate deterioration at some point in time after the onset of the illness, the consistent correlational relationship between cognitive and adaptive deficit would suggest that adaptive functioning should also be found to decline. In support of this idea, previous research on adaptive deficit in geriatric poor-outcome patients has found older patients to be more impaired (Harvey et al., 1997a), although this could be related to normal aging-related declines in adaptive skill. The current report presents preliminary data from a longitudinal study of the correlation between changes in adaptive functioning and changes in cognitive functioning. A sample of geriatric patients with schizophrenia received a clinical assessment while hospitalized in a longstay psychiatric hospital and were then seen again after their discharge from the hospital and referral to a nursing home. All of the patients were examined with ratings of positive and negative schizophrenia symptoms, adaptive functions, and cognitive impairments, and the correlations
between these variables at baseline and over time were calculated. Our hypotheses were that: (1) declines in cognitive functioning would predict declines in adaptive skill, and (2) changes in cognitive functioning would be more strongly correlated than any other variables with changes in adaptive functioning.
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-IIIR diagnoses of schizophrenia. The entire assessment procedure for that study has been published, and all subjects in this study were diagnosed and assessed with that procedure (Davidson et al., 1995, 1996). Patients had previously been excluded at prior assessments for the presence of any disorders that ruled out DSMIIIR schizophrenia, including mental retardation, substance dependence, neurological diseases or damage, and other psychiatric diagnoses. All patients who had been uncooperative with testing or who had a Mini-Mental Sate Examination (MMSE; Folstein et al., 1975) score of 0 had been excluded at the initial or follow-up assessments. The subjects in this particular component of the study had been diagnosed and assessed while in chronic psychiatric care and then had been discharged from the hospital to a nursing home. All of these patients were participants in the initial Davidson et al. (1995) paper. These patients are not included in the sample of nursing home patients with schizophrenia reported by Harvey et al. (1998) since those patients were all recruited and assessed for the first time in nursing home care. Patients were re-evaluated at the nursing home where they were in residence for 1–5 years after their discharge (mean=2.6 years). All of the subjects in this study had been hospitalized for at least 10 consecutive years before their discharge to
79
P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
the nursing home (range=11–58), and none of the patients in this study had an onset age for schizophrenic symptoms of later than 45 or earlier than 16. All patients were receiving typical neuroleptic medication at their initial assessment, and three patients had been changed to risperidone by the time of the reassessment. These three patients were excluded from the current analysis because of previous findings suggesting that risperidone treatment may enhance cognitive functioning in late-life schizophrenia (Berman et al., 1996). As a result, there were 57 patients with full assessment data. Table 1 presents demographic information on the patients. This information includes medication status, including antipsychotic medications, anticholinergic medications, sedatives, and medication for physical illness, at each of the two assessments of the patients. Consistent with our previous research (Harvey et al., 1997b; White et al., 1997),
we also collected and presented information on treatment of several different physical illnesses, including cardiac problems (hypertension and ischemic problems), diabetes, and pulmonary conditions. 2.2. Cognitive and clinical assessment All subjects were examined in the hospital with a variety of clinical and cognitive assessments, of which the current battery is a subset. Patients were examined with the Mini-Mental State Examination (MMSE; Folstein et al., 1975). This instrument is a 30-point scale that assesses a variety of cognitive functions, including orientation, registration, concentration, delayed recall, and verbal skills. Our previous research found an inter-rater reliability (intraclass correlation; ICC ) of 0.99 in this population. Schizophrenia symptoms were examined with
Table 1 Descriptive information on patients at both assessments Gender distribution (percentage male)
44
Racial ethnic distributions Caucasian African-American Hispanic
84 11 5
Age at baseline Age at first psychiatric admission Years of education completed
9.7
Mean
SD
77.8 30.7 3.2
8.2 13.7
Baseline Medications and dosages Antipsychotic (Chlorpromazine equivalent) Anticholinergic (Benztropine dose) Benzodiazipines Anticonvulsants Treatment for physical illnesses Cardiac Pulmonary Diabetes
Percentage receiving 100 9
Follow-up Mean
SD
60.4
10.6
1.0
14 5
—
Percentage receiving 95 5
Mean
SD
64.4
11.8
1.0
2 5 Baseline (percentage receiving) 21 5 4
No patients received treatment with lithium or SSRI antidepressants at either assessment.
Follow-up (percentage receiving) 28 4 4
—
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the Positive and Negative Syndrome Scale (PANSS; Kay, 1991). The PANSS contains 30 items, with seven items rating positive symptoms, seven rating negative symptoms, and 16 other items assessing ‘general psychopathology’. The rating procedures and reliability of the assessments in schizophrenic patients have been described previously (Davidson et al., 1995). For the purposes of this study, we examined the total scores on the Positive and Negative Subscales as the dependent variables. 2.3. Adaptive functioning All patients were rated with the Social-Adaptive Functioning Evaluation (SAFE; Harvey et al., 1997a) scale by trained raters from the research team. 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 five-point (0–4) scale, on the basis of the raters’ condensation of their observation of the patient, reading of the chart, and caregiver report. Raters interviewed a member of the treatment team at both the nursing home and the psychiatric hospital in order to obtain the caregiver report. Adaptive deficits receive a score of 0 if there is no impairment and 4 if there is severe and incapacitating impairment. According to the instructions for the SAFE scale, patients who had no opportunity to perform behaviors in a skills domain (e.g. no relatives to call on the telephone; restricted to ward and not permitted to move around the hospital grounds) are not rated on that item. None of the patients in the current sample were in such a situation. At the time of the reassessment, raters were unaware of the results of the previous evaluations of the patients. The interrater reliability ( ICC ) of the ratings for the individual items of the scale, based on 50 patients, ranged from a low of 0.87 to a low of 0.98 (all p<0.001) and 1 week test–retest reliability (ICC ) ranged from 0.59 to 0.86. Total score ICCs were 0.99 for both interrater and test–retest reliability. The dependent variable for this study was the total score, reflecting adaptive functioning across all 17 items.
3. Results Table 1 presents information on subjective descriptive characteristics, including medication treatment. As can be seen in the table, the patterns of medical illness and treatment with psychotropic and anticholinergic medication were essentially identical at each of the two assessments of the patients. The only patients who received new medications at the nursing home were three patients who received new treatment with cardiac medications. In addition, fewer patients received benzodiazipine medications at the nursing home than at the state psychiatric hospital. Table 2 presents the scores for the PANSS subscales, the MMSE, and the SAFE scale total scores at the baseline and follow-up assessments. T-tests were used to test for change in the symptoms over time. As shown in the table, a significant degree of worsening in both MMSE scores and in SAFE scale total scores was found over the follow-up period. For both positive and negative subscales, there was no significant change over the follow-up period. In order to perform the correlational analyses, change scores from baseline to follow-up were calculated. Pearson product-moment correlations were calculated between SAFE scale change scores and baseline and change scores on PANSS positive, PANSS negative symptoms subscales and the MMSE, as well as with baseline scores on the SAFE scale. These correlations are presented in Table 3. As can be seen in Table 3, there were only two statistically significant predictors of SAFE scale change scores: baseline levels of adaptive functioning deficits and MMSE change scores. In order to determine whether any of the other variables accounted for variance in SAFE scale change scores, a forward entry stepwise regression was computed. All variables in Table 2 were entered into the equation. The overall regression was significant [F(2,54)=10.26, p<0.001]. Only two variables entered the equation, change in MMSE scores, accounting for 34% of the variance, followed by baseline scores on the SAFE scale, accounting for 16% of the variance. Thus, when the influence of other variables is controlled, the
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84 Table 2 Clinical symptoms, cognitive impairments, and adaptive deficits over the follow-up period Baseline
Positive and Negative Syndrome Scale Positive Negative Mini-mental State Examination Social and Adaptive Functioning Evaluation Total Score
Table 3 Correlations between baseline and change scores on assessment measures Changes in SAFE Scale scores Baseline scores PANSS positive PANSS negative MMSE SAFE Scale Change scores PANSS positive PANSS negative MMSE
0.18 0.07 −0.03 0.41* 0.19 0.17 −0.49**
*p<0.01. **p<0.001.
importance of changes in MMSE for the prediction of SAFE scale scores appears even more salient. The correlations between several other variables and SAFE scale change scores were calculated, in order to determine whether there were any other factors that were associated with changes in adaptive functioning. The length of the follow-up interval, r=0.12, baseline age, r=0.10, age at follow-up, r=0.12, age at first psychiatric admission, r=−0.03, and dose of antipsychotic medication at follow-up, r=0.04 were all uncorrelated with decline in adaptive functioning as measured by the SAFE scale.
4. Discussion Moderate levels of cognitive and adaptive decline are found in geriatric patients with schizophrenia over an average of approximately 2.5 years
Follow-up
Mean
SD
Mean
SD
t
p
18.23 32.21 9.76 45.62
5.56 9.06 7.32 11.01
18.11 32.05 5.94 50.00
5.52 7.12 7.91 11.15
0.18 0.16 4.77 2.81
ns ns 0.001 0.05
after referral to nursing home care. These declines are intercorrelated and are not associated with the baseline severity of positive or negative symptoms. Since positive and negative schizophrenia symptoms did not worsen for the group as a whole over the follow-up period, there was no realistic possibility of their predicting declines in adaptive functioning. The declines in adaptive functioning are not associated with the length of the follow-up interval and are not simply due to aging. The level of cognitive and adaptive decline seen is less than expected in a similar follow-up period in patients with Alzheimer’s Disease (AD). According to previous research (e.g. Morris et al., 1993), patients with AD would be expected to decline by as much as six MMSE points in a similar time period, a rate of decline that is three times as great as that seen in our patients with schizophrenia. In addition, these changes in adaptive status do not appear to be related to changes in treatment for psychiatric symptoms or physical illness status. There are some limitations of this study. All patients were chronic patients with a very poor outcome who had severe cognitive impairments at baseline. Previous studies of better outcome patients found much higher MMSE scores in their patients ( Klapow et al., 1997) and limited evidence of age effects on cognitive functioning (Heaton et al., 1994; Palmer et al., 1997). The researchers who performed those studies found significant correlations between MMSE scores and adaptive functioning deficit, however ( Klapow et al., 1997). Since the magnitude of change in MMSE scores on average is inconsistent with that seen in degenerative dementia due to Alzheimer’s Disease and the prevalence of AD at postmortem has been
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P.D. Harvey et al. / Schizophrenia Research 35 (1999) 77–84
reported to be only 10% in schizophrenic patients from this same sample with severe cognitive impairments (Powchik et al., 1998; Purohit et al., 1998), it seems necessary to conclude that some degenerative process associated with chronic schizophrenia is responsible for the observed change in cognitive and adaptive functioning. There are several possible mechanisms that might cause the changes in cognitive and adaptive functioning seen. A stepwise pattern of decline in cognitive and functional status in some very poor outcome geriatric schizophrenic patients has previously been reported in the patients from our sample who were not discharged from the psychiatric hospital to nursing care (Harvey et al., in press). In that study, it was found that approximately 30% of patients appeared to manifest discrete periods of cognitive decline that did not occur progressively across several consecutive years. In progressive dementing conditions such as AD, adaptive skills have been shown to decline concurrently to or slightly after changes in cognitive functioning, with the results of this study indicating that this same process may occur in some elderly patients with very poor outcome schizophrenia (Mortimer et al., 1992; Green et al., 1993). The finding of deterioration in cognitive and functional status in poor outcome patients is consistent with very recent reports of progressive increases in cortical ventricular size in childhood onset (Rapoport et al., 1997), first episode (Delisi et al., 1997), and chronic (Davis et al., 1998) schizophrenia over relatively brief follow-up periods. The mechanism of brain changes and cognitive decline is not clear, although it has been suggested that extended periods of symptomatic exacerbation may cause neurodegeneration through glutamate excito-toxicity (Olney and Farber, 1995). This model would suggest that periods of exacerbation would precede cognitive decline, which would then lead to increased impairments in adaptive functioning. An additional possibility is that somehow these declines in cognitive and functional status are associated with the process of deinstitutionalization and referral to alternative residential care. This explanation is rendered somewhat implausible because of the lack of change in
positive and negative symptoms. Similarly, previous research in the UK has found that some longstay patients’ symptoms improve after discharge from long-term psychiatric care (Leff et al., 1994). If a process of global psychological reaction to environmental events was responsible for the current cognitive decline, then it is difficult to explain why both positive and negative symptoms would be unaffected. The SAFE scale is designed for use in institutional settings such as nursing home care, so declines caused by psychometric artifacts are unlikely. The issue of environmental versus biological mechanisms of cognitive decline cannot, however, be resolved by the current study. Later research, in addition to focusing on the causes of this correlated cognitive and adaptive decline, should examine the reversibility of adaptive decline. Since several recent studies have indicated that cognitive deficits may be improved by treatment with atypical neuroleptic medications (e.g. Berman et al., 1996; Green et al., 1997), longitudinal research should examine the consequences of such treatment on adaptive functioning deficit. These studies should include studies of the facilitation of rehabilitation treatments through reversal of cognitive barriers to treatment. Also important is the possibility of spontaneous reversal of adaptive deficits by improvement of cognitive impairments. It may be that the performance of previously acquired adaptive skills is impaired by cognitive dysfunction, with these skills being performed more adequately after the reversal of cognitive impairment through pharmacological treatment.
Acknowledgments This research was supported by grant number MH46436 awarded to Dr Davidson and by the assessment core (P.D. Harvey, PI ) of the Mt. Sinai Mental Health Clinical Research Center ( K.L. Davis, PI ). The authors would like to 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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