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Biomedical subjects

D V Jeste

Publications and source records attributed to D V Jeste.

At least 73 records · Page 4Linked to original sources

Alzheimer's disease and its management in the year 2010.

By 2010 the number of cases of Alzheimer's disease and other dementias will have increased by at least 25 percent. Alzheimer's disease poses an enormous threat to health service and public health resources. Three areas that require targeted research are early detection and recognition, biological markers and diagnosis, and pharmacotherapy. Care of patients with Alzheimer's disease in managed care organizations must be improved through a combination of research, education, advocacy, and legislation. Research in the pathogenic cascade of events within the brain leading to Alzheimer's disease has advanced, and treatment targets within the steps of the process have been specified. The current drug discovery and testing infrastructure is insufficient for major advances in therapy by 2010. Strategies for achieving an optimum outcome by then include increased funding of targeted research; expansion of drug discovery and therapeutic testing efforts; increased training of basic, clinical, and translational scientists; and study of optimum health care delivery systems.

Aged↗

Older patients with schizophrenia: challenges in the coming decades.

The number and proportion of older adults with schizophrenia will increase considerably in the coming decades. Although a vast literature on schizophrenia among younger adults exists, much less is known about late-life schizophrenia and its treatment. The authors describe two potential scenarios for 2011, the year that the first baby boomers will turn 65. To ensure that the more favorable scenario becomes a reality, the authors suggest four goals: decrease medical comorbidity and mortality among younger patients with schizophrenia and improve their access to health care so that they can live longer and more productive lives; improve our understanding of the neurobiological and psychosocial factors underlying late-life schizophrenia, as well as the health care and social service needs of such patients; develop more effective and safer pharmacologic, psychosocial, and cognitive behavioral treatments; and improve rehabilitation of older people with schizophrenia. Specific strategies to foster these goals include establishing a consortium for studies of late-life schizophrenia; conducting multicenter studies of treatment effectiveness; and forming interdisciplinary collaborations among researchers, clinicians, government and industry representatives, and patient advocacy groups.

Aged↗

The potential impact of the baby-boom generation on substance abuse among elderly persons.

Little attention has been paid to substance use disorders in the elderly population. Currently available diagnostic criteria are likely to significantly underestimate the prevalence of substance abuse among elderly persons because they were developed and validated in younger samples. As baby boomers age, the number of elderly persons who misuse or abuse illicit drugs and alcohol may increase because this age cohort has higher rates of use of these substances than previous cohorts. Abuse and misuse of prescription and over-the-counter drugs may also increase due to the larger numbers of baby boomers. Few studies have addressed treatment issues that may be unique to elderly substance abuse patients. Some evidence suggests that substance abuse treatment outcomes are poorer among individuals with cognitive impairment, and special treatment strategies are needed for elderly persons with dementia. To identify the magnitude of the problem, diagnostic criteria should be modified and national survey data should be analyzed to provide more accurate estimates of substance abuse and dependence among baby boomers.

Aged↗

Training in geriatric mental health: needs and strategies.

This paper examines current numbers of U.S. mental health care professionals in psychiatry, psychology, social work, and nursing who are trained to treat late-life mental disorders and presents estimates of the increased numbers that will be needed by 2010. Strategies that may be effective in increasing the supply of geriatric mental health specialists are expanding incentives, such as fellowship stipends, loan forgiveness programs, and clinical reimbursement, to attract more clinicians to the field; encouraging professional organizations to offer certification in aging to highlight increased knowledge among professionals; and increasing core curricula in late-life mental disorders, or at least in aging, in all health professions. Other strategies are to diversify the range of training opportunities available by establishing short-term training initiatives to meet specific demands; use new technology to provide education to both professionals and the public; and establish "centers of excellence" to advance research training and clinical care in late-life mental disorders.

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Abnormal involuntary movements in neuroleptic-naive children and adolescents.

OBJECTIVE: To determine the prevalence of and identify risk factors for abnormal involuntary movements in a well-characterized community sample of neuroleptic-naive children and adolescents. METHOD: The Abnormal Involuntary Movement Scale (AIMS) was administered to 390 subjects aged 3-17 years who were in foster care. Additional instruments were used to assess intellect and behaviour problems. RESULTS: A total 12.6% of subjects had at least 1 rating of "mild" movements on AIMS; these included 4.1% with at least 2 ratings of "mild" or 2 of "moderate" severity. Significant risk factors for movement disorder were younger age, lower IQ, and more severe behaviour problems. The abnormal movements were usually orofacial, and the affected subjects were generally unaware of these movements. CONCLUSION: The base prevalence of abnormal involuntary movements must be considered in children and adolescents assessed for medication in order to determine the true rate of motor side effects.

Adolescent↗

Cognitive deficits and psychopathology in institutionalized versus community-dwelling elderly schizophrenia patients.

We evaluated psychiatric symptoms and neurocognitive functioning among 25 institutionalized and 25 outpatient DSM-IV-diagnosed schizophrenia patients, as well as 25 middle-aged and elderly normal comparison subjects. All subjects were assessed with the Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, modified Simpson-Angus Extrapyramidal Symptom Scale, the Abnormal Involuntary Movement Scale, and the Mattis Dementia Rating Scale (DRS). The two patient groups had similar levels of depressive symptoms, but the institutionalized patients had more severe positive and negative symptoms and were on higher doses of neuroleptic medication. The institutionalized patients had significantly more cognitive impairment on the DRS than outpatients and normal comparison subjects, particularly on the subscales of initiation/perseveration, conceptualization, and memory. Results are discussed in terms of the possible neuropathology associated with cognitive impairment in chronic schizophrenia.

Aged↗

Gender-related clinical differences in older patients with schizophrenia.

BACKGROUND: Gender differences in the clinical presentation of young patients with schizophrenia have been well-documented, yet few studies have investigated gender-related clinical differences in older patients. Furthermore, the symptoms of late-onset schizophrenia have been described, but the interaction between gender and age at onset has not been examined. METHOD: In an older (46-85 years of age) outpatient sample, we assessed clinical characteristics of women and men with early-onset schizophrenia (N = 90) and late-onset schizophrenia (N = 34). Subjects did not differ with respect to age, education, ethnicity, severity of depression, daily neuroleptic dosage, subtype of schizophrenia, total score on the Mini-Mental State Examination, or severity of overall psychopathology. Diagnosis was made using the Structured Clinical Interview for the DSM-III-R or DSM-IV. RESULTS: A significantly greater proportion of women had late-onset schizophrenia (41% vs. 20%), and women overall had more severe positive psychotic symptoms. Although there was no overall gender difference in severity of negative psychotic symptoms, women with late onset had significantly less severe negative symptoms than men with early onset, men with late onset, and women with early onset. Furthermore, age at onset of schizophrenia was inversely correlated with severity of negative symptoms for women, but not for men. These results indicate that women overall may develop more severe positive symptoms than men, and that when women develop schizophrenia after age 45, they may suffer less severe negative symptoms than men or than women with earlier onset. Our results suggest that some of the clinical differences between late-onset and early-onset schizophrenia may relate to gender effects, and that there may be inherent differences in the clinical presentation of schizophrenia that are related to gender and gender by age at onset interactions. CONCLUSION: These differences may reflect the influence of sex hormones and menopause on the clinical presentation of schizophrenia or the possible existence of an "estrogen-related" form of schizophrenia in women with late-onset schizophrenia.

Adult↗

Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group.

BACKGROUND: We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia. METHOD: 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). RESULTS: The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients. CONCLUSION: Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.

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Schizoaffective disorder: a form of schizophrenia or affective disorder?

BACKGROUND: The diagnostic status of schizoaffective disorder continues to be controversial. Researchers have proposed that schizoaffective disorder represents a variant of schizophrenia or affective disorder, a combination of the 2, or an intermediate condition along a continuum between schizophrenia and affective disorder. METHOD: We compared outpatients aged 45 to 77 years with DSM-III-R diagnosis of schizoaffective disorder (N = 29), schizophrenia (N = 154), or nonpsychotic mood disorder (N = 27) on standardized rating scales of psychopathology and a comprehensive neuropsychological test battery. A discriminant function analysis was used to classify the schizoaffective patients based on their neuropsychological profiles as being similar either to schizophrenia patients or to those with nonpsychotic mood disorder. RESULTS: The schizoaffective and schizophrenia patients had more severe dyskinesia, had a weaker family history of mood disorder, had been hospitalized for psychiatric reasons more frequently, were more likely to be prescribed neuroleptic and anticholinergic medication, and had somewhat less severe depressive symptoms than the mood disorder patients. The schizophrenia patients had more severe positive symptoms than the schizoaffective and mood disorder patients. The neuropsychological performances of the 2 psychosis groups were more impaired than those of the nonpsychotic mood disorder patients. Finally, on the basis of a discriminant function analysis, the schizoaffective patients were more likely to be classified as having schizophrenia than a mood disorder. CONCLUSION: These findings suggest that schizoaffective disorder may represent a variant of schizophrenia in clinical symptom profiles and cognitive impairment.

Aged↗

Conventional vs. newer antipsychotics in elderly patients.

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Adult↗

Correlates of functional status in older patients with schizophrenia.

There is a growing recognition of the importance of quantifying the impact of illness on functional abilities. Measures of function frequently rely on a self-report. Few studies have directly assessed functional capacity in psychiatric patients, especially older ones who may be at an increased risk for disability. Subjects were 102 middle-aged and elderly outpatients with DSM-III-R or DSM-IV diagnosis of schizophrenia or schizoaffective disorder, and 66 normal comparison subjects, ranging in age from 45 to 86. The Direct Assessment of Functional Status (DAFS), a standardized measure of behavior during simulated daily activity tasks (i.e. time orientation, communication, transportation, finance, shopping, grooming and eating) was used to quantify levels of disability. Schizophrenic patients demonstrated significantly greater disability than normal subjects. An evaluation of specific behaviors indicated that the patients were significantly more limited than comparison subjects across all subscales of the DAFS except for grooming and eating. A lower level of formal education, greater severity of extrapyramidal symptoms, and greater cognitive deficits, but not severity of symptoms of schizophrenia, were related to lower DAFS scores. Relative to published findings, schizophrenic patients appeared more disabled than outpatients with major depression, but less disabled than those with Alzheimer's disease. The DAFS is a useful instrument for characterizing functional abilities in older patients with schizophrenia. Our findings of significant functional disability in older schizophrenic patients have implications for treatment as well as allocation of health-care resources.

Activities of Daily Living↗

Relationship between auditory P300 amplitude and age of onset of schizophrenia in older patients.

Auditory P300 amplitude reductions are well-established in young adults with schizophrenia. Little is known, however, regarding the P300 in older schizophrenia patients, especially those with late onset. We studied 28 middle-aged and elderly (mean age = 62.7 years) patients [14 with early onset schizophrenia (EOS) and 14 with late onset schizophrenia (LOS)] and 14 normal comparison (NC) participants using an auditory oddball paradigm. Event-related potentials were recorded from 15 scalp electrodes and six non-scalp sites. There were no significant differences between EOS and LOS groups in neuroleptic dosage, symptom severity, reaction times, target-detection accuracy, or N100 and N200 ERP measures. The EOS, but not the LOS, group had significantly smaller auditory oddball P300 amplitudes than the NC group. Twelve of the 14 LOS patients had P300 amplitudes in the normal range. Smaller P300 amplitudes were associated with earlier age of onset (r = 0.48), longer duration of illness (r = -0.49) and more severe alogia (r = -0.50). We conclude that P300 abnormalities in schizophrenia may be a marker for a disease subtype with early onset and more severe information-processing deficits.

Age of Onset↗

Diagnostic validity of the dementia questionnaire for Alzheimer disease.

OBJECTIVE: To determine the sensitivity and specificity of postmortem dementia diagnoses based on a retrospective informant interview by comparison with criterion standard neuropathological diagnoses and the results of previous clinical examinations. SETTING: Three university-based academic research centers. SUBJECTS: Fifty-four deceased elderly persons with Alzheimer disease, another dementing disorder, a neurologic disease resulting in functional impairment but no dementia, or no neurologic disorder. METHODS: Blinded nonclinician interviewers administered the Dementia Questionnaire (DQ) by telephone to informants, typically close relatives, who were familiar with the intellectual and functional status of the subjects before death. Two senior clinicians (LJ.T. and C.K.) rated each DQ for the presence or absence of a dementia syndrome during life and for the specific disorders causing the dementia, if present. Raters were blinded to the neuropathological findings and based their assessments only on data provided by responses to the DQ. Comparison was made with diagnoses based on neuropathological assessment. In most cases, the results of antemortem clinical examinations were also available as a check on the clinical diagnosis of the dementia syndrome. Sensitivity and specificity of the DQ diagnoses were computed, and chance-corrected agreement measures were calculated for the 2 independent DQ raters (LJ.T. and C.K.). RESULTS: Compared with antemortem clinical diagnosis, the average sensitivity of the DQ for the clinical syndrome of dementia was 92.8%, the specificity was 89.5%, and the interrater agreement was 98% (kappa = 0.96). Among 7 subjects with mild dementia (Mini-Mental State Examination score > or = 24 at the last clinical examination), 5 (71%) were correctly identified using the DQ. The DQ correctly indicated the absence of dementia in 8 (80%) of 10 subjects with other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the DQ differentiated Alzheimer disease from other primary causes of dementia with a sensitivity of 89% and a specificity of 72%. The interrater agreement was 93.8% (kappa = 0.85). CONCLUSIONS: Compared with the results of the antemortem clinical examinations, the DQ was sensitive to the presence of dementia, detected most cases of mild dementia, and discriminated dementia from other neurologic disorders causing functional impairment. Compared with the neuropathological diagnoses, the ability of the DQ to differentiate Alzheimer disease from other dementing disorders indicates that it may be useful as a research tool.

Aged↗

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia.

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-III-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Adult↗

Assessment and treatment of bipolar disorder in the elderly.

The aetiology of late-onset bipolar disorder is heterogeneous because the disease is more likely to have a secondary (i.e. a medical disorder or medication-induced) cause in older than in younger patients. Elderly patients with bipolar disorder typically require lithium dosages that are 25 to 50% lower than those used in younger individuals. Information on the use of valproic acid (sodium valproate) in elderly patients with bipolar disorder is limited but encouraging. In contrast, there is virtually no information regarding the use of carbamazepine or other drugs in this patient group. Electroconvulsive therapy is well tolerated by older people and can be useful for these patients.

Aged↗

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.

Aged↗

Review of functional magnetic resonance imaging in schizophrenia.

Functional magnetic resonance imaging (fMRI) holds great promise for assessing temporal changes in brain activity using various challenge paradigms. In this report, we review the 14 studies (eight of them abstracts) that comprise the fMRI literature available to date relating to schizophrenia. Twelve of the 14 investigations examined changes in blood-oxygen-level-dependent (BOLD) contrast: two examined blood volume. Eight of the 12 BOLD studies relied on lower-order cognitive processing to measure activation (involving sensory or motor areas), whereas four used higher-order tasks (word production, auditory processing, and subspan word recall involving multiple brain areas). Although the variability in tasks used, brain regions studied, imaging methods used, patient characteristics reported, and methods of reporting significance precluded a full meta-analysis, we re-analyzed these published data to compute effect sizes. In most studies, resting blood volume and BOLD changes, regardless of the complexity of the cognitive task, appeared to differ between patients with schizophrenia and control subjects.

Brain↗