Elizabeth W. Twamley

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.

Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

OBJECTIVE Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. METHOD We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. RESULTS 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. CONCLUSIONS Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention.

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.

Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease.

Alzheimers disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular.

Neuropsychological function in female victims of intimate partner violence with and without posttraumatic stress disorder

BACKGROUND Various aspects of neuropsychologic function have been reported to be abnormal in patients with posttraumatic stress disorder (PTSD); however, the majority of these data come from studies of seriously ill, treatment-seeking samples with substantial substance use comorbidity. Few studies have included similarly trauma-exposed subjects without PTSD, and fewer still have focused on women. METHODS Thirty-nine female victims of intimate partner violence (IPV; 22 without lifetime PTSD and 17 with current PTSD), and 22 nonvictimized comparison (NC) subjects were administered tests of attention, working memory, visuoconstruction, language ability, learning and memory, and executive functioning. RESULTS The IPV and NC subjects did not demonstrate statistically significant differences on most neuropsychologic tests, with the exception of those in the realm of working memory, visuoconstruction, and executive functioning. The IPV subjects, regardless of PTSD status, had poorer performance on tasks of speeded, sustained auditory attention and working memory (Paced Auditory Serial Addition Test) and response inhibition (Stroop). The IPV subjects with PTSD performed worse than NCs on a set-shifting task (Trail Making Test, Part B). No consistent relationships were noted between neuropsychologic functioning and severity of childhood abuse or domestic violence experiences. CONCLUSIONS Cognitive deficits in IPV subjects were confined to measures of working memory, visuoconstruction, and executive function; were subtle; and were not uniformly worse among those with current PTSD. This pattern, however, is consistent with frontal-subcortical dysfunction in traumatized women. The clinical significance of these findings deserves further study.

Subjective and objective quality of life in schizophrenia

OBJECTIVE Quality of life (QOL) is considered an important outcome in the treatment of schizophrenia, but the determinants of QOL are poorly understood in this population. Furthermore, previous studies have relied on combined measures of subjective QOL (usually defined as life satisfaction) and objective QOL (usually defined as participation in activities and relationships). We examined separately the clinical, functional, and cognitive predictors of subjective and objective QOL in outpatients with schizophrenia. We hypothesized that better subjective QOL would be associated with less severe negative and depressive symptoms, better objective QOL, and greater everyday functioning capacity, and that better objective QOL would be associated with less severe negative and depressive symptoms, better cognitive performance, and greater functional capacity. METHOD Participants included 88 outpatients with schizophrenia or schizoaffective disorder who completed a comprehensive series of assessments, including measures of positive, negative, and depressive symptoms; performance-based functional skills; a neuropsychological battery; and an interview measure of subjective and objective QOL. RESULTS In the context of multiple predictor variables, more severe depressive symptoms and better neuropsychological functioning were independent predictors of worse subjective QOL. More severe negative symptoms predicted worse objective QOL. Functional capacity variables were not associated with subjective or objective QOL. CONCLUSION Treatments to improve QOL in schizophrenia should focus on negative symptoms and depressive symptoms.

Validating the Measurement of Real-World Functional Outcomes: Phase I Results of the VALERO Study

OBJECTIVE Treatment of cognitive impairment has been proposed as an intervention to reduce disability in people with schizophrenia. The Validation of Everyday Real-World Outcomes (VALERO) study was conducted to evaluate functional rating scales and to identify the rating scale or scales most robustly related to performance-based measures of cognition and everyday living skills. METHOD Adults with schizophrenia (N=198) were tested with the neurocognitive measures from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, the UCSD Performance-Based Skills Assessment-Brief Version, and the advanced finances subscale of the Everyday Functioning Battery. They and an informant (a friend, relative, clinician, or case manager) also reported their everyday functioning on six rating scales. Best judgment ratings were generated by an interviewer who administered the rating scales to patients and informants. RESULTS Statistical analyses developed an ability latent trait that reflected scores on the three performance-based (i.e., ability) measures, and canonical correlation analysis related interviewer ratings to the latent trait. The overall fit of the model with all six rating scales was good. Individual rating scales that did not improve the fit of the model were systematically deleted, and a final model with two rating scales was fitted to the data. A regression analysis found that the Specific Levels of Functioning Assessment was a superior predictor of the three performance-based ability measures. CONCLUSIONS Systematic assessments of real-world functioning were related to performance on neurocognitive and functional capacity measures. Of the six rating scales evaluated in this study, the Specific Levels of Functioning Assessment was the best. Use of a single rating scale provides an efficient assessment of real-world functioning that accounts for considerable variance in performance-based scores.

Neuropsychological function in college students with and without posttraumatic stress disorder

Previous research on the neuropsychology of posttraumatic stress disorder (PTSD) has identified several neurocognitive deficits that co-occur with the disorder. However, it remains unclear whether these deficits are due to trauma exposure, PTSD symptomatology or psychiatric/substance abuse comorbidity. We examined trauma exposure, PTSD symptoms and neuropsychological performance in 235 undergraduate students, i.e. a non-clinical sample. The sample comprised 146 subjects with trauma exposure (38 with current PTSD and 108 without lifetime PTSD) and 89 no-trauma comparison (NC) subjects who were administered tests of attention, working memory, psychomotor speed, word generation and executive functioning. Relationships of neuropsychological functioning to measures of psychiatric symptoms and substance abuse were examined. Current PTSD (PTSD+), trauma-exposed without PTSD (PTSD-) and NC subjects did not differ significantly on the vast majority of neuropsychological tests. There were very few significant associations between neuropsychological performance and clinical variables, and those that were statistically significant were small in magnitude. The striking lack of differences in neuropsychological performance between the three groups suggests that college students with trauma exposure, regardless of the presence of PTSD symptoms, may be cognitively resilient. Neuropsychological impairment may not be an invariant feature of PTSD, but when it is present, it may be associated with poorer functional outcomes.

Aging and outcome in schizophrenia

Objective:  Controversy exists about long‐term outcome of schizophrenia, but few studies have compared older out‐patients to normal subjects. We sought to examine the relationship of age to clinical features, psychopathology, movement abnormalities, quality of well‐being, and everyday functioning in schizophrenia out‐patients and normal comparison subjects, and to further characterize these outcomes in elderly schizophrenia out‐patients.

Dorsolateral Prefrontal Cortex Activation During Emotional Anticipation and Neuropsychological Performance in Posttraumatic Stress Disorder

CONTEXT Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. OBJECTIVE To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. DESIGN Case-control, cross-sectional study. SETTING General community and hospital and community psychiatric clinics. PARTICIPANTS Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. MAIN OUTCOME MEASURES We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. RESULTS Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. CONCLUSIONS During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.