Biomedical subjects
P Powchik
Publications and source records attributed to P Powchik.
Cognitive functioning in chronically hospitalized schizophrenic patients: age-related changes and age disorientation as a predictor of impairment.
Although schizophrenic patients manifest cognitive impairments, there is considerable variability across patients in the severity of this impairment. Very chronic patients with a poor outcome, particularly geriatric patients, manifest the most severe impairments, which have often been characterized as resembling dementia. This study examined age-related changes in cognitive functioning in a sample of schizophrenic patients (n = 393) ranging from 25 to 95 years of age, with a specific focus on identifying aspects of performance that were impaired in the youngest patients and preserved in the oldest patients. Age disorientation was examined in detail because it was previously found to predict global intellectual impairment in chronic patients. All 22 test items changed linearly over time (with age), with aspects of orientation, concentration, and delayed recall most impaired in young patients and naming and sentence repetition most preserved in the oldest patients. Age disoriented patients had more severe cognitive impairments at each age and the age-related changes in global impairment were more severe for these patients. The prevalence of age disorientation was consistent with previous reports and a one-year retest of the sample found that age disorientation was extremely stable over time within patients. The types of functions that are preserved in the oldest patients underscore previous findings of differences between geriatric schizophrenic patients and patients with degenerative diseases and the stability of age disorientation suggests that it is a trait of a subset of schizophrenic patients, those who appear to have the most severely declining course of illness.
Severity of symptoms in chronically institutionalized geriatric schizophrenic patients.
OBJECTIVE: The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence. METHOD: The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years. RESULTS: In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed. Significant correlations between Mini-Mental State scores and Positive and Negative Syndrome Scale negative symptom scores, but not positive symptom scores, were found for all age groups, except for the youngest patients studied. Current treatment with neuroleptics and prior treatment with ECT, insulin coma, or leukotomy could not account for the poor cognitive performance of the older schizophrenic patients. CONCLUSIONS: The older schizophrenic patients continued to experience psychotic and nonpsychotic symptoms in senescence. Their positive symptoms were moderately less severe and their negative symptoms and cognitive impairment were significantly more severe than those of the younger patients. Somatic treatment appeared not to be responsible for the severe cognitive impairment and negative symptoms of the older patients. These data are relevant to chronically hospitalized geriatric schizophrenic patients but not necessarily to all geriatric schizophrenic patients.
Validity and utility of the ADAS-L for measurement of cognitive and functional impairment in geriatric schizophrenic inpatients.
This study examined the usefulness of the Alzheimer's Disease Assessment Scale-Late Version (ADAS-L) for assessing cognitive and behavioral impairment in geriatric schizophrenic patients. Subjects were 339 geriatric schizophrenic inpatients. Discriminant function analyses compared the Mini-Mental State Examination (MMSE) with the ADAS-L as independent variables predicting the level of impairment on the criterion measure, the Clinical Dementia Rating. The ADAS-L surpassed the MMSE at correctly distinguishing severe to profound impairment; the MMSE was superior for identifying absent or questionable impairment. Findings provide evidence for the concurrent validity of the ADAS-L as an instrument for measuring impairment in geriatric schizophrenic inpatients.
Memory functions in geriatric chronic schizophrenic patients: a neuropsychological study.
This study characterized memory functions in geriatric schizophrenic inpatients with a battery of memory tests sensitive to neuropsychological impairments in either temporal or frontal brain regions. In patients clinically rated as cognitively impaired (n = 24), nearly all of these measures showed deficits relative to less impaired patients (n = 25). Factor analysis found consistent correlations between the tests and their putative cortical localization. Discriminant analysis suggested the pattern of impairments was not consistent with a generalized deficit. These results introduce the possibility, to be directly tested with neuropathological study, that the severe cognitive deficits in elderly schizophrenic patients are due to dysfunctions in either the temporal or frontal regions of the cerebral cortex, with the specific type of dysfunction varying across cases.
The longitudinal stability of cognitive impairment in schizophrenia. Mini-mental state scores at one- and two-year follow-ups in geriatric in-patients.
BACKGROUND: Severe cognitive impairment affects many patients with schizophrenia, especially geriatric in-patients. Little is known about the course of this impairment, however. METHOD: Two hundred and twenty-four geriatric schizophrenic in-patients were examined for changes in cognitive functioning over a one-year follow-up period, and 45 of them were assessed over a two-year period. In addition, the subset of 45 patients participated in a one-week and one-month test-retest reliability study of the instrument used to assess cognitive impairment, the Mini-Mental State Examination (MMSE). RESULTS: The average MMSE scores did not change over a one- or two-year follow-up period. The test-retest reliability of the scale was extremely good at both retest intervals. CONCLUSION: Among the implications of these data are that cognitive changes in geriatric schizophrenic patients are very slow and are more consistent with a neurodevelopmental process than a neurodegenerative course.
Cortical cholinergic markers in schizophrenia.
Cortical cholinergic deficits have been implicated in the cognitive deficits produced by a variety of neurodegenerative diseases including Alzheimer's disease (AD). Recent studies have suggested that many of the chronically institutionalized geriatric schizophrenic patients are also cognitively impaired. In this postmortem study we compared cholinergic marker activity in six different cortical regions derived from elderly controls, chronically institutionalized geriatric schizophrenic patients, and AD patients. All of the Alzheimer's disease cases met neuropathological criteria for AD, while none of the schizophrenic cases met criteria for AD. Cholinergic marker activity (choline acetyltransferase and acetylcholinesterase) was significantly diminished in the AD cohort but not in the schizophrenic cohort. Additionally, cortical choline acetyltransferase activity was significantly and negatively correlated with Clinical Dementia Rating scores (CDR), whereas no such correlations were evident in the schizophrenic cohort. These results suggest that cognitive deficits in geriatric schizophrenics are not due to diminished cortical cholinergic activity.
Severe cognitive impairment in elderly schizophrenic patients: a clinicopathological study.
The severe cognitive impairment that affects many of the elderly schizophrenic patients could represent the outcome of schizophrenia in old age for the very severe and chronically ill patients or may be the result of lengthy institutionalization and somatic treatment. Alternatively, it could be due to the presence of concurrent dementing disorders, such as Alzheimer's disease (AD) or multi-infarct dementia. Using an identical neuropathological protocol, brain specimens from schizophrenic patients who showed evidence of severe cognitive impairment were compared with 12 age-matched control cases and the same number of age-matched cases of neuropathologically confirmed patients with AD. Despite their relatively advanced age (mean age 77.1 years +/- 2.8), none of the schizophrenia cases showed sufficient degree of senile plaques and neurofibrillary tangle formations to confirm a diagnosis of AD. Other neurodegenerative disorders associated with dementia were also not identified. These studies suggest that alternative explanations need to be sought for the severe cognitive impairment commonly encountered in elderly schizophrenic patients.
Alzheimer's-disease-related protein in geriatric schizophrenic patients with cognitive impairment.
The authors compared Alz-50 immunoreactivity in the brain tissue of nine cognitively impaired elderly schizophrenic patients and 13 elderly comparison subjects, both without neuritic plaques or neurofibrillary tangles, and 13 patients with Alzheimer's disease. Alz-50 reactivity was absent in the schizophrenic patients, indicating that geriatric, cognitively impaired patients are unlikely to display the pathology of Alzheimer's disease.
Assessment of dementia in elderly schizophrenics with structured rating scales.
Although a number of elderly institutionalized schizophrenic patients appear to suffer from dementia, little is known about the characteristics of the cognitive impairment or its prevalence in this population. In order to answer these questions it is necessary to first reliably and validly assess dementia in elderly schizophrenic patients. This paper reports the results of a study examining the reliability of assessments of the severity of dementia in schizophrenia using scales designed for other dementing conditions and examining the convergence of ratings of the severity of dementia generated from all available sources of information (patient, caregiver, and chart) versus the chart alone. It was found that the interrater reliability of these ratings was very high. On the other hand ratings generated from the hospital chart alone, without contact with either the patient or caregiver, manifested a systematic bias toward overestimation of the severity of dementia. These results suggest that dementia assessment in schizophrenia does not require different instrumentation from that used in other conditions but that relying on the medical chart alone would induce a systematic bias in the results.
Changes in plasma homovanillic acid concentrations in schizophrenic patients following neuroleptic discontinuation.
Changes in plasma levels of the dopamine metabolite homovanillic acid have been reported to correlate with changes in the severity of schizophrenic symptoms during neuroleptic administration and after neuroleptic discontinuation. This study examined the effects of discontinuation of neuroleptic treatment on plasma homovanillic acid levels in 23 patients with chronic schizophrenia. It was hypothesized that clinical decompensation would be associated with increased plasma homovanillic acid levels. Plasma homovanillic acid was measured during administration of neuroleptic medication and during a subsequent 6-week drug-free period. Nine patients decompensated during the drug-free period and 14 patients did not. Following drug discontinuation, plasma homovanillic acid concentrations were higher in schizophrenic patients who decompensated than in those who did not. Furthermore, peak plasma homovanillic acid elevation after discontinuation of neuroleptic medication was significantly correlated with peak Brief Psychiatric Rating Scale increase. The data suggest that, in some schizophrenic patients, symptomatic decompensation after discontinuation of neuroleptic treatment is associated with increases in dopamine turnover.
Brief neuroleptic discontinuation and clinical symptoms in Kraepelinian and non-Kraepelinian chronic schizophrenic patients.
Neuroleptic medication was abruptly discontinued in 24 male chronic schizophrenic patients who were subdivided on the basis of their history of illness into Kraepelinian (n = 8) and non-Kraepelinian (n = 16) subgroups. These patients were kept drug free for 6 weeks and then returned to treatment with haloperidol, 20 mg/day. Half of the non-Kraepelinian patients developed exacerbations of their symptoms, which quickly resolved when they were returned to medication, while none of the Kraepelinian patients showed a worsening of symptomatology. On-medication clinical severity failed to predict risk for exacerbation, with severity of exacerbation predicting the amount of improvement when returned to medication. The Kraepelinian patients were found to be much less variable than the non-Kraepelinian patients in their symptoms during both medication manipulations, suggesting that medication truly has a negligible effect on them.
Time course and clinical predictors of treatment response in schizophrenia.
The severity of schizophrenic symptoms was examined in 50 male chronic patients while neuroleptic free for at least 3 weeks and during 6 weeks of treatment with haloperidol. The results suggested that 50% of the improvement associated with haloperidol administration occurred by the end of the first treatment week and that early improvement, at both 1 and 4 weeks of treatment, was predictable from drug-free symptom severity. There was a negative correlation between week 1 improvement and improvement during the next 3 weeks of treatment, suggesting that medication response is not linear. Finally, dose increases after 4 weeks of treatment with 20 mg of haloperidol did not lead to any clinical improvement. These results are discussed in terms of their implications for selecting chronic schizophrenic patients who will and will not benefit from medication treatment.
Effects of the D-1 agonist SKF-38393 combined with haloperidol in schizophrenic patients.
Explore the source record for details and available documents.
Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.
1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.
4-Aminopyridine in the treatment of Alzheimer's disease.
The cognitive and behavioral effect of 4-aminopyridine (4-AP) was examined in Alzheimer's disease (AD) using a dose finding/replication study design. Fourteen inpatients, aged 54-89 years (mean 66.1 +/- 10.6 SD), meeting NINCDS criteria for probable AD, were studied. Three doses of 4-AP--2.5 mg b.i.d., 5 mg b.i.d., and 10 mg b.i.d.--or placebo were administered for 4 consecutive days in random order. Symptomatic assessment was performed on the fourth day of each condition using the Alzheimer Disease Assessment Scale (ADAS). Thereafter, the dose on which the best performance occurred was readministered, as was placebo. Of the 13 patients who completed the dose-finding phase, 7 patients had at least one dose of 4-AP that was associated with less severe symptoms than was placebo, and those patients were included in the replication phase. Results indicated no significant difference in total ADAS scores (p greater than 0.05). Examination of the ADAS subscales revealed no significant 4-AP effect on any particular symptom. Possible explanations of the lack of a drug effect in this study include the unselective release of neurotransmitters by 4-AP, poor penetration into the central nervous system (CNS), and the presenile onset of the disease in these patients.
Pisa syndrome in Alzheimer's disease.
Explore the source record for details and available documents.
Short-term haloperidol administration acutely elevates human plasma homovanillic acid concentration.
Explore the source record for details and available documents.