Biomedical subjects

M P Caligiuri

Publications and source records attributed to M P Caligiuri.

At least 19 recordsLinked to original sources

PubMed2003

Neuromotor abnormalities and risk for psychosis in Alzheimer's disease.

BACKGROUND: Cross-sectional studies in Alzheimer's disease (AD) show a strong relationship between extrapyramidal motor signs and presence of psychosis, yet it remains unclear whether neuromotor abnormalities precede and therefore can predict development of psychosis in AD. OBJECTIVE: To identify cognitive and motor risk factors for the development of psychosis in patients with AD. METHODS: Baseline clinical motor ratings and instrumental measures of neuromuscular function were obtained from 54 nonpsychotic patients with AD who were evaluated annually for 2 years for the development of psychosis. Survival analyses were performed to identify incidence and risks associated with psychosis. RESULTS: The incidence of new onset psychosis in our sample was 32.5% in 2 years. Patients with abnormal agonist muscle burst amplitudes during rapid alternating movements of the hand were more likely to develop psychosis than those without (OR = 4.31; p = 0.007). Women with AD also had a higher risk of developing psychosis within 2 years than men (OR = 1.33; p = 0.01). CONCLUSIONS: Using simple noninvasive instrumental procedures for assessing neuromotor function, it may be possible to identify an individual's level of risk for developing psychosis during the course of AD.

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PubMed2001

Extrapyramidal signs and cognitive abilities in Alzheimer's disease.

OBJECTIVE: To evaluate whether the relationship between extrapyramidal signs (EPS) and cognitive disturbances in Alzheimer's disease (AD) is influenced by illness duration. METHODS: A multivariate regression analysis was used to study the relationships between EPS, illness duration and five cognitive ability areas based on the Mattis Dementia Rating Scale (DRS) in 89 clinically diagnosed AD patients with extrapyramidal motor involvement. RESULTS: Severity of EPS was statistically associated with performance on four cognitive ability areas from the DRS including: attention, initiation and perseveration, construction and memory. Age was a significant factor related to severity of EPS. However illness duration did not contribute to the strength of the association between EPS and cognitive disturbances in patients with AD. CONCLUSIONS: The findings of the present study support the notion that while neuropsychological and motor functions often coexist in patients with AD, their relationship seems to be unrelated to degenerative processes that accumulate throughout the illness.

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PubMed2001

Relationship of gender and age at onset of schizophrenia to severity of dyskinesia.

The authors examined severity of dyskinesia in 119 men and 44 women, comparing by gender those with late-onset schizophrenia (LOS) versus early-onset schizophrenia (EOS). Women with LOS and men with EOS had more severe dyskinesia than men with LOS and women with EOS. Many factors, including the length of neuroleptic treatment, alcohol and smoking history, and menopausal status, may contribute to the severity of dyskinesia in older patients with schizophrenia.

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PubMed2000

Neuroleptic-induced striatal damage in rats: a study of antioxidant treatment using accelerometric and immunocytochemical methods.

RATIONALE: Investigators have postulated that neuroleptic medications may affect the motor system through the creation of free radicals. Also, structural brain changes related to oxidative damage may disrupt normal striatal function. OBJECTIVE: The goals of this study were to examine whether an antioxidant diet reduced the abnormal movements caused by long-term neuroleptic exposure and to examine structural effects within specific striatal regions in rats. METHODS: Rats were given a basal diet or a diet high in antioxidants for 4 months, and treated with 10 mg/kg fluphenazine decanoate or sesame seed oil IM every 2 weeks. At baseline and after treatment, head movements were quantified by accelerometry, and immunocytochemically stained cholinergic neurons in the ventrolateral, mediodorsal, and ventromedial regions of the striatum were quantified. RESULTS: Rats treated with fluphenazine had significantly lower neuron densities than those that did not receive antioxidants. Rats exposed to a diet consisting of antioxidants had significantly higher neuron densities than those that did not receive antioxidants in each of the three regions tested. Rats treated with fluphenazine had a greater increase in the number of accelerometric peaks recorded per minute compared with untreated animals. The increase in the number of accelerometric peaks recorded per minute was lower for animals exposed to antioxidant diets compared with unexposed animals. Lastly, there was a significant correlation between the accelerometric peak change score and cholinergic neuron density in all three regions. CONCLUSIONS: Our results suggest that long-term neuroleptic treatment is associated with an increase in head movements and a reduction in ChAT-stained striatal cholinergic neurons and that these abnormalities are reduced by antioxidants.

Animals↗

PubMed2000

Instrumentally detected changes in motor functioning in patients with low levels of antipsychotic dopamine D2 blockade.

Extrapyramidal side-effects (EPSE) of antipsychotic medication are related to the occupancy of dopamine D2 receptors and there appears to be a threshold of D2 occupancy below which clinically EPSE are unlikely to occur. It is unclear whether there are motor changes produced by 'subthreshold' levels of D2 occupancy that are not detectable by clinical examination. This study was designed to investigate whether a number of electromechanical instrumental techniques could detect 'subthreshold' motor changes and whether these changes correlate with dopamine D2 occupancy as measured by [11C]-raclopride PET scan. Twenty medication naïve patients were studied before and during treatment with low dose haloperidol. Instrumental techniques detected an asymmetrical worsening in motor function with drug treatment despite the failure of the group to experience significant EPSE. These changes did not correlate with D2 occupancy and measurements of rigidity, tremor, and bradykinesia did not closely inter-correlate.

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PubMed2000

An instrumental study of the relationship between extrapyramidal signs and psychosis in Alzheimer's disease.

Neurobehavioral disturbances often coexist with extrapyramidal signs (EPS) in patients with Alzheimer's disease (AD). In the present study, we examined the relationships between delusions and hallucinations and EPS by using standard observer ratings and sensitive electromyographic (EMG) measures in 52 patients with probable AD. On the basis of observer ratings, 36.5% of the patients exhibited psychotic features and 63.5% exhibited parkinsonism. Severity of clinically rated parkinsonism and the EMG measure of bradykinesia were significantly correlated with severity of neurobehavioral disturbances in this sample. The association between parkinsonism and delusions and hallucinations suggests a subcortical mechanism in the etiopathology of psychosis in AD.

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PubMed1999

Incidence and predictors of drug-induced parkinsonism in older psychiatric patients treated with very low doses of neuroleptics.

The available literature suggests that a sizable proportion of patients placed on neuroleptics develop acute and subacute extrapyramidal side effects, including neuroleptic-induced parkinsonism (NIP). The presence of mild, spontaneous extrapyramidal signs in the elderly makes it difficult to accurately estimate the incidence of NIP in this subgroup of patients. We examined the incidence of NIP in 56 older, newly medicated, psychiatric patients. Fifteen age-comparable, unmedicated psychiatric patients underwent 2 assessments to estimate natural fluctuation in extrapyramidal signs, and 49 normal, healthy, elderly individuals were also studied to establish age-comparable norms for the assessment of parkinsonism. Potential pretreatment predictor variables included instrumental measures of motor function, age, cognitive status, and psychiatric diagnosis. After controlling for spontaneous parkinsonism, 32% of patients met strict criteria for NIP after receiving an average of 43 mg/day chlorpromazine equivalents of a typical neuroleptic. Factors contributing to the development of NIP included older age, instrumentally derived tremor, baseline extrapyramidal signs, type of neuroleptic, and severity of dementia. The use of risperidone in a small subsample was not associated with NIP. These findings indicate that even after controlling for spontaneous extrapyramidal signs at baseline and their natural fluctuations, there is a substantial risk of NIP in older patients who are treated with very low doses of typical neuroleptics.

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PubMed1999

Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients.

OBJECTIVE: To compare the 9-month cumulative incidence of tardive dyskinesia (TD) with risperidone to that with haloperidol in older patients. DESIGN: A prospective longitudinal study. SETTING: An outpatient psychiatric clinic. PARTICIPANTS: Subjects were middle-aged and older (mean age 66 years) patients with schizophrenia, dementia, mood disorders, or other conditions with psychotic symptoms or severe behavioral disturbances. Sixty-one patients on risperidone were matched with 61 patients from a larger sample of haloperidol-treated patients in regard to age, diagnosis, and length of pre-enrollment neuroleptic intake to create clinically comparable groups. The median daily dose of each medication was 1.0 mg. MEASUREMENTS: Abnormal Involuntary Movement Scale, modified Simpson-Angus' scale for extrapyramidal symptoms, Brief Psychiatric Rating Scale, and Mini-Mental State Examination were administered at baseline, 1 month, and 3, 6, and 9 months. The diagnosis of TD was based on specific research criteria. The raters were blind to the patient's medication status. RESULTS: Life table analysis revealed that patients treated with haloperidol were significantly more likely to develop TD than patients treated with risperidone (P < .05, Peto-Prentice). CONCLUSIONS: The atypical antipsychotic risperidone is significantly less likely to result in TD than the conventional neuroleptic haloperidol in a high-risk group of older patients, at least over a 9-month period.

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PubMed1999

Incidence of tardive dyskinesia in early stages of low-dose treatment with typical neuroleptics in older patients.

OBJECTIVE: The authors studied the risk of tardive dyskinesia for older patients in the early stages of treatment with typical neuroleptics. METHOD: They examined the cumulative incidence of tardive dyskinesia 1, 3, 6, 9, and 12 months after the institution of neuroleptic therapy among 307 psychiatric outpatients over age 45. The patients' median dose was 68.4 mg/day of chlorpromazine equivalent. RESULTS: In the patients who had never received neuroleptics at baseline (N = 87), the mean cumulative incidence of tardive dyskinesia was 3.4% and 5.9% at 1 and 3 months, respectively. There was no significant difference in the 12-month cumulative incidence of tardive dyskinesia among patients who had been neuroleptic-naive at baseline (22.3%) and the 89 patients who had received neuroleptics before baseline for 1-30 days (24.6%); however, the 131 patients who had received neuroleptics before baseline for more than 30 days tended to have a greater cumulative 12-month incidence of tardive dyskinesia (36.9%). CONCLUSIONS: The risk of tardive dyskinesia in older outpatients is high, even with relatively short treatment with low doses of conventional neuroleptics.

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PubMed1998

Extrapyramidal side effects in patients with Alzheimer's disease treated with low-dose neuroleptic medication.

The authors examined whether the presence of extrapyramidal side effects (EPS), measured before neuroleptic treatment was initiated, could be used to predict the development and severity of neuroleptic-induced parkinsonism (NIP) in Alzheimer's disease (AD). Twenty-four newly medicated probable AD patients were assessed with a battery of measures of extrapyramidal motor function. Assessments were made before neuroleptic therapy, and 3 and 9 months after treatment. Posttreatment clinical findings revealed that 66.7% of the AD patients developed NIP. Patients who developed NIP exhibited more severe pretreatment bradykinesia on instrument-derived measures. These findings suggest that a substantial proportion of AD patients treated with neuroleptics develop significant EPS and that the risk for EPS can be estimated before intervention by use of instruments measuring motor function.

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PubMed1998

Scaling of movement velocity: a measure of neuromotor retardation in individuals with psychopathology.

The study of motor slowness based on observational methods has limitations. Whether motor retardation has a psychomotor or neuromotor basis is unclear because psychiatric and motor symptoms overlap. Observational methods lack the precision necessary to distinguish cognitive from motor processes. For the present study, we used an objective measure of neuromotor dysfunction to quantify the extent to which an individual programs movement velocity in anticipation of increasing target distance. Persons with Parkinson's disease (PD) or functional psychosis were studied with a group of healthy comparison subjects. Results indicated that the slope of the linear function relating velocity to distance was abnormal in the PD group and in approximately half of the psychosis group. Analyses revealed the measure to have high specificity and sensitivity. Weak correlations between velocity scaling and psychopathology support the neuromotor basis of the measure. We conclude that this measure of velocity scaling is relatively uninfluenced by cognitive factors that may underlie psychomotor retardation.

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PubMed1997

Lateralized hemispheric dysfunction in the major psychotic disorders: historical perspectives and findings from a study of motor asymmetry in older patients.

Differences in functioning between the two cerebral hemispheres have been reported for more than a century. In recent decades, issues related to lateralized dysfunction have been raised in psychiatric illnesses such as schizophrenia and bipolar disorder. In particular, evidence suggests that schizophrenia may be particularly associated with left hemisphere dysfunction and bipolar disorder with right hemisphere dysfunction. We discuss these issues, along with a conceptual framework for integrating hypotheses about the relationship between the major psychotic illnesses based on a two-dimensional continuum. We also present new findings from our study of motor asymmetry in older patients with psychosis that support this framework. Our results indicate that schizophrenia may be associated with left hemisphere pathology to a greater extent than right, whereas the reverse may occur in bipolar disorder.

Age Factors↗

PubMed1997

Reliability of an instrumental assessment of tardive dyskinesia: results from VA Cooperative Study #394.

Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted by the Department of Veteran Affairs Cooperative Studies Program. One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient. In the present report, we describe the training procedures and results of a multi-center reliability assessment of this procedure. Data from nine study centers comprising 45 individual patients with six trials each (three from left hand and three from right hand) were reanalyzed by an independent investigator and the results were subjected to reliability assessment. For the statistic of interest (average coefficient of variation over trials 2 and 3 for each hand, then take the larger of these two values), we found very high intraclass correlation coefficients for reliability over all patients across sites (ICC = 0.995). We also calculated the reliability of the measures across trials within patient for each combination of hand (right, left, dominant), rater group (site, control), and trials set (all three, trials 2 and 3). For a given hand and trial set, the reliability of the site raters was similar to that of the control. This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training.

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PubMed1997

An association between increased serum-soluble interleukin-2 receptors and a disturbance in muscle force in schizophrenic patients.

1. Serum-soluble interleukin-2 receptors (SIL-2Rs), a sign of immune activation, are increased in approximately 30% of schizophrenic subjects. 2. In a recent publication the authors found that SIL-2Rs were particularly elevated in schizophrenic subjects with tardive dyskinesia (TD). 3. This paper investigates the relationship between muscle force instability and SIL-2Rs in 32 schizophrenic patients, 10 of whom were neuroleptic-naive. 4. The authors hypothesized that there would be a positive correlation between increased levels of SIL-2Rs and muscle force instability. 5. Serum SIL-2Rs and muscle force instability were positively correlated (r = 0.54, p < .001) in the schizophrenic patients, and this correlation held even for the subset of neuroleptic-naive patients (r = .73, df 8, p = .016). 6. These findings suggest that there is an important correlation between immune activation and muscle force instability in schizophrenic patients.

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PubMed1997

Instrumental motor predictors of neuroleptic-induced parkinsonism in newly medicated schizophrenia patients.

Previous studies suggest that many untreated schizophrenia patients exhibit motor disturbances. On the basis of these findings, the authors hypothesized that preexisting extrapyramidal movement disorders may increase the risk of developing neuroleptic-induced parkinsonism (NIP). Thirty-five newly medicated psychotic patients underwent pretreatment clinical and instrumental motor and psychiatric assessments. Posttreatment ratings of parkinsonism were conducted at monthly intervals for the first 3 months and every 3 months thereafter. Thirteen patients (37%) developed NIP. Advanced age and pretreatment extrapyramidal disturbances predicted NIP. Life-table survival curves indicated that patients with pretreatment instrumental rigidity developed clinically significant NIP earlier than those without rigidity. These findings suggest that pretreatment motor dysfunction may be a risk factor for drug-induced parkinsonism, especially among older patients.

Adult↗

PubMed1997

Incidence and risk factors for severe tardive dyskinesia in older patients.

BACKGROUND: Severe tardive dyskinesia (TD) represents a serious and potentially disabling movement disorder, yet relatively little is known about the incidence of and risk factors for severe TD. METHOD: We report the results of a longitudinal prospective incidence study of severe TD in 378 middle-aged and elderly neuropsychiatric patients. Psychiatric, neuropsychological, pharmacological and motor variables were obtained at intake and at regular intervals for 36 months. RESULTS: The cumulative incidence of severe TD was 2.5% after one year, 12.1% after two years, and 22.9% after three years. Individual univariable Cox regression analyses were conducted to identify demographic, psychiatric, motor and pharmacological predictors of severe TD. Results indicated that higher daily doses of neuroleptics at study entry, greater cumulative amounts of prescribed neuroleptic, and greater severity of worsening negative symptoms were predictive of severe TD. CONCLUSIONS: These findings suggest that conventional neuroleptics may be prescribed to older patients only when necessary and at the lowest effective dosage. Additional caution is recommended in patients exhibiting negative symptoms.

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PubMed1996

Risk factors for orofacial and limbtruncal tardive dyskinesia in older patients: a prospective longitudinal study.

Although there is a consensus that orofacial and limbtruncal subtypes of tardive dyskinesia (TD) exist and may represent distinct pathophysiologic entities, few studies have examined the incidence of and risk factors associated with the development of these TD subtypes. Two hundred and sixty-six middle-aged and elderly outpatients with a median duration of 21 days of total lifetime neuroleptic exposure at study entry were evaluated at 1- to 3-month intervals. Using "mild" dyskinesia in any part of the body for diagnosis of TD, the cumulative incidence of orofacial TD was 38.5 and 65.7% after 1 and 2 years, respectively, whereas that of limbtruncal TD was 18.6 and 32.6% after 1 and 2 years. Preclinical dyskinesia was predictive of both orofacial and limbtruncal TD. History of alcohol abuse or dependence was a significant predictor of orofacial TD only whereas tremor was a significant predictor of limbtruncal TD only. Findings support suggestions that orofacial and limbtruncal TD may represent specific subsyndromes with different risk factors.

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PubMed1996

Tardive dyskinesia and positive and negative symptoms of schizophrenia. A study using instrumental measures.

BACKGROUND: Controversy surrounds the relationship between tardive dyskinesia (TD) and symptoms of schizophrenia. While some studies reported that negative symptoms of schizophrenia may be a risk factor for TD, others reported a relationship between TD and positive symptoms. METHOD: Eighty-four patients were studied, of whom 47 met criteria for TD. Clinical and instrumental procedures were used to increase the sensitivity of our assessments of the presence and severity of TD. Stepwise logistic and linear regression procedures were used to identify demographic variables, psychopathology, and motor parameters associated with the presence and severity of TD. RESULTS: A 3-factor model consisting of age, clinical tremor, and negative symptoms explained 25% of the variance in clinical TD severity. A 6-factor model consisting of female gender, instrumental and clinical measures of parkinsonism, positive, and negative symptoms explained 49% of the variance in severity of instrumentally derived dyskinesia. CONCLUSIONS: These results suggest that the presence of TD may be associated with positive symptoms; that the severity of TD may be related to negative symptoms; and that the relationship between negative symptoms and TD severity may be influenced by the presence of parkinsonism.

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