Patrick J. Moriarty

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity

BACKGROUND Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Practice-related improvement in information processing with novel antipsychotic treatment

BACKGROUND Attentional deficits are prominent in schizophrenia, and skill learning is impaired. Novel antipsychotic treatment has been reported to improve certain cognitive skills in schizophrenic patients, but no information is yet available about the effect of newer medications on skill learning. METHODS Clinically stable patients with schizophrenia (n=16) and chronically hospitalized inpatients (n=8) were recruited while receiving conventional antipsychotic treatment. Subjects were tested at baseline on a visual continuous performance test (CPT), performed alone and simultaneously with an auditory CPT. Normal controls (n=8) were also tested at baseline. The inpatients and half of the outpatients were switched to treatment with risperidone. All patients then performed the visual CPT on a daily basis and performed the dual tasks once per week, for 4weeks. RESULTS Patients who remained on conventional medications did not improve in their performance despite the extensive practice on the test. Both chronic and stable patients receiving risperidone treatment manifested a statistically significant (P<0.05) improvement from baseline on both single and dual-task visual CPT. Stable outpatients performed significantly better at the end of the protocol than the normal controls performance at baseline (P<0.05). IMPLICATIONS These results suggest that practice-related improvements in the performance of information processing tests are enhanced by novel antipsychotic medications. Although the specific biological mechanism of this effect is not yet known, the results may suggest that use of newer medications will enhance skill development and perhaps facilitate rehabilitation of patients with schizophrenia.

Cognitive assessment of geriatric schizophrenic patients with severe impairment.

There is evidence that some elderly patients with chronic schizophrenia experience marked impairments in cognitive functioning. Assessment of these patients may be difficult with traditional neuropsychological measures. The purpose of the present study was to determine if cognitive functioning could be validly assessed with the Alzheimers Disease Assessment Scale-Late Version Cognitive factor score (ADAS-L Cog) in patients whose scores on the Mini-Mental State Examination (MMSE) reflect profound cognitive impairment. Patients with MMSE scores from 0 to 10 were selected from a larger database. Neuropsychological instruments designed for the assessment of mild to moderate dementia were found to be inadequate in this profoundly impaired population, due to floor effects. In contrast, there was a significant relationship between ADAS-L scores and several criterion measures, including the MMSE (R=-.71, P<.001), the Social Adaptive Functions Evaluation (SAFE) social functions scale (R=.47, P<.001), and the negative symptom total score of the Positive and Negative Syndrome Scale (PANSS) (R=.412, P<.001). The MMSE was somewhat less strongly correlated with both social functions (R=-.401, P<.001) and the negative symptom total score of the PANSS (R=-.366, P<.001). These results suggest that cognition can be reliably and validly assessed with instruments such as the ADAS-L that are designed for the assessment of severely impaired patients.

A comprehensive analysis of verbal fluency deficit in geriatric schizophrenia.

Deficits in verbal fluency are common in schizophrenia and may provide keys to some of the abnormalities in the semantic system in schizophrenia. While a number of studies have outlined the severity and implications of verbal fluency deficits in younger schizophrenia patients, these findings have not yet been extended to older patients with schizophrenia. In this study, 392 older (age >/= 50) patients with schizophrenia were administered phonological and semantic (i.e., category) fluency examinations, as well as tests of learning, memory, language, and praxic skills, and rated for clinical symptoms and functional status. When compared to normative standards, 82% of the patients were impaired in semantic fluency and 83% were impaired in phonological fluency. Both semantic and phonological fluency impairment were significantly correlated with other cognitive variables, total scores on the functional status measure, and with the social and self-care subscales. Scores were uncorrelated with the severity of psychosis, but were correlated with the severity of negative symptoms. Furthermore, the severity of poverty of speech (a clinical measure of verbal underproductivity) was moderate in magnitude and failed to enter as a predictor of verbal fluency, indicating that impaired fluency scores are not simply an artifact of general underproductivity or mutism. The findings support conclusions from studies with younger schizophrenia patients that suggest that verbal fluency impairment is a consequence of a disorganized semantic system. Verbal fluency impairment remains common and functionally relevant in schizophrenia patients in late life.

Reduced Processing Resource Availability in Schizotypal Personality Disorder: Evidence From a Dual-Task CPT Study

Performance on a dual-task information processing task was investigated in 23 schizotypal personality disorder patients (SPD), 29 patients with other noncluster A personality disorders (OPD) and 8 nonpsychiatric healthy controls (NC). All participants were assessed using a computer-based visual continuous performance test (CPT) and an auditory CPT individually, and administered again simultaneously in a dual-task condition. The SPD group showed a greater increase in the number of errors of omission than the OPD group or normal controls on the CPT tasks in the dual-task conditions. Performance operating characteristics indicated that the SPD patients did not allocate their attention in a manner different from the healthy controls, suggesting that poorer performance was due to resource limitations in the dual task condition and not strategic failures. These results are similar to previous studies of patients with schizophrenia, where performance deficits on information processing tests have been shown to be related to resource limitations more than failures in effective allocation of attention.

Cortical and Subcortical Cognitive Deficits in Schizophrenia: Convergence of Classifications Based on Language and Memory Skill Areas

Cortical and subcortical dementias have been reported to have distinct neuropsychological profiles. Previous studies of patients with schizophrenia have examined the memory-based profiles associated cortical and subcortical dementias. Although these two types of dementias have both language and memory-based profiles, the current study is the first to examine the overlap in classification associated with memory based and language based classifications. In this study, elderly (age >64 years) patients with schizophrenia (n =239) who varied in their lifetime outcome from chronic institutional care to stable community residence were tested with a neuropsychological battery that examined language and memory performance. Using a large sample of normal controls previously tested with this same assessment, normative standards for performance were developed. Schizophrenic patients were divided into cortical versus subcortical versus unimpaired groups on the basis of language and memory performance. Classification overlap ranged from a high of 30% (cortical profile) to a low of 14% (unimpaired profile). Furthermore, patients classified on the basis of verbal and memory ability areas did not differ in their performance in measures from the other ability areas. Data from a 1-year follow-up of part of the sample (n =147) suggested poor stability of the subcortical classification in particular. These data suggest that cortical versus subcortical profiles of cognitive performance in schizophrenia are inconsistent across ability areas, and are not likely to be the result of stable structural or functional brain deficits.

108. Neurocognitive predictors of functional decline in poor-outcome schizophrenia

Although cognitive abilities have been shown to be directly related to social, occupational, and adaptive functioning in patients with schizophrenia, there is no evidence indicating that a specific neuropsychological index can predict decline in functional status. Impairments in verbal learning and memory, verbal skills, and executive functions correlate with functional impairments, and are predictive of functional ability over time. Yet, there is no evidence that impairment on a specific neurocognitive index is associated with functional decline, or whether these measures are all associated with functional impairments due to a global or specific cognitive deficit. In order to test whether any of these neuropsychological measures (Verbal Learning and Memory, Praxis, and Confrontational Naming) is most associated with functional decline, 68 subjects were chosen from a long-term study of the effects of aging in schizophrenia. Subjects were chosen specifically because they declined functionally from a mildly impaired level of functioning to a moderate or severely impaired level of functioning across two assessments (mean interval 5 1.89 years, sd 5 1.42 years), based on a global rating of functioning on the Clinical Dementia Rating Scale (CDR). Age and education corrected z-scores were derived for measures of verbal learning, delayed memory, praxic ability, and confrontational naming, based on performance of healthy controls on these measures as part of the Consortium to Establish a Registry of Alzheimer’s Disease (CERAD). Change in performance on these neuropsychological measures was calculated by subtracting the standardized z-score of each measure at the follow-up assessment from the standardized score obtained on each measure at the initial assessment. A repeated measures ANOVA was used to determine if any of these measures were specifically associated with functional decline. Whereas the overall ANOVA was significant (F(1, 67) 5 14.49, p , .001), no specific measure of neurocognitive functioning was able to account for the decline in functional ability (Rao’s R (3, 65) 5 1.19, p , .321). These data suggest that the cognitive decline seen in these patients is generalized, rather than selective. It may be that this functional decline is related to low levels of cortical decline in patients with poor premorbid functioning and a chronic clinical course of illness.

371. Convergence of cognitive and adaptive decline in chronic schizophrenia

Cognitivedysfunctionhas been found to be comelatedwith adaptive functioningdeficitsin schizophrenia. Despitethe fact that manychrotic patients with a particularlypoor outcome have evidence of grossly impairedadaptiveandcognitiveskillsthatimplicatedeclineat sometime period,little evidencehas beerrcollectedto identifythe timingof any decline. Since most studies evaluatingthe associationbetween these domainshavebeencross-sectional,convergenceof adaptiveand cognitivedeclinehasnotbeendemonstrated. In thisstudy,59geriatricpatients withchronicschizophreniawerefollowedupfrom1to 6 yearsatler their referralfromchronicpsychiatriccare toa nursinghomein the community.Positiveand negativeschizophrenicsymptoms(measuredwiththe PANSS),cognitivefunctioning(measuredwiththe MMSE),andsocirdadaptivefunctioning(measuredwith the Social AdaptiveFunctioning Evaluation[SAFE]Scale)wereassessedat thesetwotimeperiods.Both MMSEscores and SAFEscale scores showedevidenceof statistically significant worsening(both p .05), as was the durationof the followup interval(r= –.02). Changesin MMSEscores over the followupperiod were significantly correlated with changes in adaptive functions, r= –.49, p<.001. Thesedata indicatethat thosepatientswhodeclinein adaptive functioningare also manifestingdeteriorationin cognitive status.The averagelevelof changein MMSEscores,2.0pointsoveran averagefollowupperiodof2.5years,is inconsistentwiththedeclineseen in degenerativeconditionssuchas Alzheimer’sDisease.