Dilip V. Jeste

Is it possible to be schizophrenic yet neuropsychologically normal

This study identified and characterized a group of schizophrenic patients without neuropsychological (NP) impairment. A comprehensive NP battery was administered to 171 schizophrenic outpatients and 63 normal comparison participants. Each participants NP status was classified through blind clinical ratings by 2 experienced neuropsychologists; 27% of the schizophrenics were classified as NP normal. The NP-normal and NP-impaired schizophrenics were similar in terms of most demographic, psychiatric, and functional characteristics, except that NP-normal patients had less negative and extrapyramidal symptoms, were on less anticholinergic medication, socialized more frequently, and were less likely to have had a recent psychiatric hospitalization. The existence of NP-normal schizophrenics suggests that the pathophysiology underlying the cognitive deficits often associated with schizophrenia may be distinct from that causing some of its core psychiatric features.

Cognitive training in Alzheimer's disease: a meta‐analysis of the literature

Objective:  To systematically review the literature and summarize the effect of cognitive training (CT) for Alzheimers disease (AD) patients on multiple functional domains.

The nature of learning and memory impairments in schizophrenia.

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n = 175) performed worse than normal comparison (NC) subjects (n = 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimers disease (AD)], subcortical dementia [i.e., Huntingtons disease (HD)], and normals, it was found that 50% of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology.

Vocational rehabilitation in schizophrenia and other psychotic disorders: a literature review and meta-analysis of randomized controlled trials.

Although most individuals with schizophrenia are unemployed, plentiful evidence suggests that work rehabilitation is effective for this population. Yet, there have been only 11 published randomized controlled trials of work rehabilitation interventions for people with severe mental illness. We review these 11 studies, 9 of which were trials examining Individual Placement and Support (IPS) or supported employment (SE) interventions. Outcomes strongly favored the experimental groups in terms of the percentage of participants who worked at any point during the studies (weighted mean effect size = 0.66). In the 5 investigations comparing IPS/SE to conventional vocational rehabilitation services, 51% of the participants receiving IPS/SE worked competitively, versus 18% of those in the comparison groups (weighted mean effect size = 0.79). This effect size may be a useful benchmark for future trials. Further investigations should examine individual differences as predictors of response, to identify modifiable versus nonmodifiable factors that yield better outcomes.

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6–1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a ‘black box’ warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.

Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies

Objective: To determine whether AD neurofibrillary pathology influences clinical diagnostic accuracy in dementia with Lewy bodies (DLB). Background: Pathologic diagnosis of DLB mandates Lewy bodies but also allows for AD pathology in the form of plaques and tangles. Because clinical diagnostic accuracy of DLB remains low, the authors questioned whether the severity of AD pathology in the form of tangles might affect the clinician’s ability to correctly diagnose DLB in life. Design/Methods: Ninety-eight subjects with autopsy-proven DLB who had been evaluated annually at the University of California San Diego AD Research Center were identified. The clinical diagnosis used was the last diagnosis before death. Pathologic diagnosis of DLB was made according to Consensus guidelines, and Braak staging was used to assess the degree of neurofibrillary AD pathology. The clinical characteristics of subjects with DLB with low vs high Braak stages were compared and the clinical diagnostic accuracy for subjects stratified according to Braak stage was determined. Results: Only 27% of the subjects with DLB demonstrated both visual hallucinations and spontaneous extrapyramidal signs (EPS). The low Braak stage (0 to 2, n = 24) subjects had a higher frequency of visual hallucinations (65%) than did subjects with DLB with higher (3 to 6, n = 66) Braak stages (33%, p = 0.008), and showed a slightly greater but not significant degree of EPS. Although clinical diagnostic accuracy for DLB was relatively low (49%), it was higher for subjects with low (75%) compared to high (39%) Braak stages (p = 0.0039). Conclusions: The degree of concomitant AD tangle pathology has an important influence on the clinical characteristics and, therefore, the clinical diagnostic accuracy of DLB.

A tune in “a minor” can “b major”: A review of epidemiology, illness course, and public health implications of subthreshold depression in older adults

BACKGROUND With emphasis on dimensional aspects of psychopathology in development of the upcoming DSM-V, we systematically review data on epidemiology, illness course, risk factors for, and consequences of late-life depressive syndromes not meeting DSM-IV-TR criteria for major depression or dysthymia. We termed these syndromes subthreshold depression, including minor depression and subsyndromal depression. METHODS We searched PubMed (1980-Jan 2010) using the terms: subsyndromal depression, subthreshold depression, and minor depression in combination with elderly, geriatric, older adult, and late-life. Data were extracted from 181 studies of late-life subthreshold depression. RESULTS In older adults subthreshold depression was generally at least 2-3 times more prevalent (median community point prevalence 9.8%) than major depression. Prevalence of subthreshold depression was lower in community settings versus primary care and highest in long-term care settings. Approximately 8-10% of older persons with subthreshold depression developed major depression per year. The course of late-life subthreshold depression was more favorable than that of late-life major depression, but far from benign, with a median remission rate to non-depressed status of only 27% after ≥1 year. Prominent risk factors included female gender, medical burden, disability, and low social support; consequences included increased disability, greater healthcare utilization, and increased suicidal ideation. LIMITATIONS Heterogeneity of the data, especially related to definitions of subthreshold depression limit our ability to conduct meta-analysis. CONCLUSIONS The high prevalence and associated adverse health outcomes of late-life subthreshold depression indicate the major public health significance of this condition and suggest a need for further research on its neurobiology and treatment. Such efforts could potentially lead to prevention of considerable morbidity for the growing number of older adults.

Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases.

Case reports and small retrospective studies suggest that atypical antipsychotic agents may be associated with new-onset Type II diabetes mellitus (DM) or diabetic ketoacidosis (DKA); however, these reports often provide limited or no information on demographic variables such as age, gender, ethnicity, relationship to weight gain, and time course. We analyzed 45 published cases of new-onset DM or DKA for which followed initiation of atypical antipsychotic treatment. Of the 45 patients, 20 had received clozapine, 19 olanzapine, 3 quetiapine, and 3 risperidone. Eighty-seven percent patients were male, and 47% African American. Forty-two percent of these patients presented as DKA, and 50% manifested no weight gain at time of presentation with DM or DKA, although 84% were overweight before antipsychotic therapy. Eighty-four percent presented within 6 months and 59% within 3 months of commencing atypical antipsychotics. The DKA cohort had significantly younger age, less overweight at baseline, and higher proportion of women than did those with DM alone, without significant differences in distribution of ethnicity, weight gain, family history of DM, or duration of exposure to atypical agents. Clinicians should be aware of the potential risks of new-onset DM and DKA in patients taking atypical antipsychotics, and utilize appropriate clinical and laboratory monitoring to prevent serious adverse events.

Incidence of and risk factors for hallucinations and delusions in patients with probable AD

Objective: To examine the incidence of and risk factors for hallucinations and delusions associated with patients clinically diagnosed with probable AD. Background: Estimates of the incidence of psychosis in AD range widely from 10% to 75%. The risk factors for psychosis of AD are not known, although multiple studies indicate that AD patients with psychosis demonstrate greater cognitive and functional impairment. Methods: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer’s Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whether there were specific risk factors for the development of hallucinations and delusions. Results: Using Cox survival analyses, the cumulative incidence of hallucinations and delusions was 20.1% at 1 year, 36.1% at 2, 49.5% at 3, and 51.3% at 4 years. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. Age, education, and gender were not significant predictors. Conclusions: The authors found a relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD and suggest that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.

Measurement and predictors of resilience among community-dwelling older women

BACKGROUND Resilience, the ability to adapt positively to adversity, may be an important factor in successful aging. However, the assessment and correlates of resilience in elderly individuals have not received adequate attention. METHOD A total of 1395 community-dwelling women over age 60 who were participants at the San Diego Clinical Center of the Womens Health Initiative completed the Connor-Davidson Resilience Scale (CD-RISC), along with other scales pertinent to successful cognitive aging. Internal consistency and predictors of the CD-RISC were examined, as well as the consistency of its factor structure with published reports. RESULTS The mean age of the cohort was 73 (7.2) years and 14% were Hispanic, 76% were non-Hispanic white, and nearly all had completed a high school education (98%). The mean total score on the CD-RISC was 75.7 (sd=13.0). This scale showed high internal consistency (Cronbachs alpha=0.92). Exploratory factor analysis yielded four factors (somewhat different from those previously reported among younger adults) that reflected items involving: (1) personal control and goal orientation, (2) adaptation and tolerance for negative affect, (3) leadership and trust in instincts, and (4) spiritual coping. The strongest predictors of CD-RISC scores in this study were higher emotional well-being, optimism, self-rated successful aging, social engagement, and fewer cognitive complaints. CONCLUSIONS Our study suggests that the CD-RISC is an internally consistent scale for assessing resilience among older women, and that greater resilience as assessed by the CD-RISC related positively to key components of successful aging.