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1.  Changes in capacity to consent over time in patients involved in psychiatric research 
The British Journal of Psychiatry  2013;202(6):454-458.
Informed consent is a key element of ethical clinical research. Patients with serious mental illness may be at risk for impaired consent capacity. Corrective feedback improves within-session comprehension of consent-relevant information, but little is known about the trajectory of patients’ comprehension after the initial enrolment session.
To examine whether within-session gains in understanding after feedback were maintained between study visits and to examine stability of decisional capacity over time.
This was a longitudinal, within-participants comparison of decisional capacity assessed at baseline, 1 week, 3 months, 12 months and 24 months in 161 people with schizophrenia or bipolar disorder.
Within-session gains from corrective feedback generally dissipated over each follow-up interval. Decisional capacity showed a general pattern of stability, but there was significant between-participant heterogeneity. Better neuropsychological performance was associated with better decisional capacity across time points. Positive symptoms of schizophrenia did not predict any aspects of decisional capacity, but general psychopathology, negative symptoms and depression evidenced some modest associations with certain subdomains of decisional capacity.
Informed consent may be most effectively construed as an ongoing dialogue with participants at each study visit.
PMCID: PMC3669878  PMID: 23661766
2.  Preliminary Study of a Web-based Tool for Enhancing the Informed Consent Process in Schizophrenia Research 
Schizophrenia research  2012;141(2-3):247-250.
Printed research consent forms serve to legally document what has been disclosed, but are usually suboptimal as a means of actually communicating that information to potential participants. We conducted a preliminary study of web-based multimedia consent. Participants included 19 patients with schizophrenia and 16 normal comparison (NC) subjects randomly assigned to a routine or web-media consent. Although comprehension among NCs was excellent regardless of consent condition, the web-based consent was associated with better comprehension and satisfaction among patients with schizophrenia. Findings suggest web-aided multimedia consent is feasible and potentially more effective than printed consent forms in schizophrenia research.
PMCID: PMC3471544  PMID: 22939457
Decisional capacity; web-aided consent; schizophrenia; multimedia consent
3.  Cognitive Profiles in Persons with Chronic Schizophrenia 
Cognitive heterogeneity has been a key barrier to clarifying the neuropathologic underpinnings of schizophrenia. We used an idiographic method for cluster analysis of neuropsychological data from 144 middle-aged and older people with schizophrenia to characterize and group the patterns of relative (within-person) profiles of cognitive strength and weakness. Results indicated a 5-cluster solution as most appropriate, with relatively even distribution across the five clusters in terms of the proportion of patients in each cluster. Cognitive subtyping may be useful in imaging and genetic research on schizophrenia, as well as having practical utility in treatment planning and cognitive rehabilitation.
PMCID: PMC3221409  PMID: 21644139
4.  Do people with schizophrenia have differential impairment in episodic memory and/or working memory relative to other cognitive abilities? 
Schizophrenia research  2009;116(2-3):259.
Efforts to identify differential or core cognitive deficits in schizophrenia have been made for several decades, with limited success. Part of the difficulty in establishing a cognitive profile in schizophrenia is the considerable inter-patient heterogeneity in the level of cognitive impairment associated with this condition. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-patient level. In the present study we examined the rates of significant intra-person differences between crystallized verbal ability versus five other cognitive abilities among 127 persons with schizophrenia or schizoaffective disorder and 127 demographically matched normal comparison (NC) subjects. We found that the rates of significant discrepancies above the NC group base-rates was significantly greater in reference to those discrepancies involving visual memory relative to those associated with auditory memory, working memory, processing speed, and perceptual organization. The findings conflict with prior suggestions that working memory or auditory episodic memory are differential or core deficits in schizophrenia, and highlight the importance of considering visual memory in characterizing the cognitive effects of this condition.
PMCID: PMC2818439  PMID: 19945256
psychosis; neuropsychology; neurocognitive; heterogeneity; idiographic
5.  Parkinson's Disease and REM Sleep Behavior Disorder Result in Increased Non-Motor Symptoms 
Sleep medicine  2014;15(8):959-966.
Rapid Eye Movement (REM) sleep behavior disorder is often co-morbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having REM sleep behavior disorder on multiple NMS in patients with PD.
86 participants were evaluated for REM-sleep behavior disorder and assessed for multiple non-motor symptoms of PD. Principal component analysis was utilized to model multiple measures of non-motor symptoms in PD and a multivariate analysis of variance was used to assess the relationship between REM-sleep behavior disorder and the multiple non-motor symptoms measures. Seven non-motor symptoms measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall non-motor symptoms of PD.
36 PD patients were classified as having REM-sleep behavior disorder (objective polysomnography and subjective findings), 26 as not having REM-sleep behavior disorder (neither objective nor subjective findings), and 24 as probable REM-sleep behavior disorder (either subjective or objective findings). REM-sleep behavior disorder was a significant predictor of increased non-motor symptoms in PD while controlling for dopaminergic therapy and age (p=0.01). The REM-sleep behavior disorder group reported more non-motor symptoms of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall non-motor symptoms (p=0.002).
In PD, REM-sleep behavior disorder is associated with more non-motor symptoms, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with REM-sleep behavior disorder represent a subtype of PD with different disease progression and phenomenological presentation.
PMCID: PMC4117926  PMID: 24938585
Parkinson's disease; REM sleep Behavior Disorder; Non-motor Symptoms; Sleep Disorders; Quality of Life; Mood; Fatigue; Daytime Sleepiness
6.  Neurodevelopmental Theories of Schizophernia : Application to Late-Onset Schizophernia 
Indian Journal of Psychiatry  1996;38(1):13-22.
A review of literature on the neurodevelopmental origins of schizophemia is presented, with particular attention to neurodevelopmental processes in late-onset schizophemia. Definitions of the term “neurodevelopmental” as used in schizophernia literature are first provided. Next, evidence for the developmental origins of the neuropathology in schizophemia is reviewed. This evidence includes studies of the associations between schizophemia and neurodevelopmental brain aberrations, minor physical anomalies, obstetric complications, prenatal viral exposure, childhood neuromotor abnormalities, and pandysmaturation. A brief discussion of the predominant theories about the neurodevelopmental origins of schizophemia is then provided. The concept and nature of “late-onset schizophenia ”is next defined and discussed. Finally, the neurodevelopmental literature is discussed in relation to the phenomenon of late-onset schizophemia. Based on this review, we conclude that there exists a strong likelihood that late-onset schizophrenia involves neurodevelopmental processes.
PMCID: PMC2970774  PMID: 21584112
Psychosis; neurodegeneration; dementia; congnition; aging; developmental disabilities
7.  A prospective study of the trajectories of clinical insight, affective symptoms, and cognitive ability in bipolar disorder 
Clinical insight in bipolar disorder is associated with treatment adherence and psychosocial outcome. The short-term dynamics of clinical insight in relationship to symptoms and cognitive abilities are unknown.
In a prospective observational study, a total of 106 outpatients with bipolar disorder I or II were assessed at baseline, 6 weeks, 12 weeks, and 26 weeks. Participants were administered a comprehensive neuropsychological battery, clinical ratings of manic and depressive symptom severity, and self-reported clinical insight. Lagged correlations and linear mixed-effects models were used to determine the temporal associations between symptoms and insight, as well as the moderating influence of global cognitive abilities.
At baseline, insight was modestly correlated with severity of manic symptoms, but not with depressive symptoms or cognitive abilities. Insight and depressive symptoms fluctuated to approximately the same extent over time. Both lagged correlations and mixed effects models with lagged effects indicated that the severity of manic symptoms predicted worse insight at later assessments, whereas the converse was not significant. There were no direct or moderating influences of global cognitive abilities.
Our sample size was modest, and included relatively psychiatrically stable outpatients, followed for a six month period. Our results may not generalize to acutely symptomatic patients followed over a longer period.
Clinical insight varies substantially over time within patients with bipolar disorder. Impaired insight in bipolar disorder is more likely to follow than to precede manic symptoms.
PMCID: PMC4011138  PMID: 24200153
Bipolar disorder; insight; neuropsychology; depression
8.  Neuropsychological Correlates of Capacity Determinations in Alzheimer’s Disease: Implications for Assessment 
To explore the neuropsychological correlates of the capacity to consent to research and to appoint a research proxy among persons with Alzheimer’s disease.
Design, Setting, and Participants
Interview study of 77 persons with Alzheimer’s disease recruited through an Alzheimer’s disease research center and a memory disorder clinic.
The capacity to consent to two research scenarios (a drug randomized clinical trial and a neurosurgical clinical trial) and the capacity to appoint a research proxy were determined by five experienced consultation psychiatrists who rendered categorical judgments based on videotaped interviews of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and the Capacity to Appoint a Proxy Assessment (CAPA). Mattis Dementia Rating Scale-2 (DRS-2) was used to assess neuropsychological functioning.
The capacity to appoint a proxy and to consent to the drug randomized clinical trial, as determined by a majority or greater opinion of the 5-psychiatrist panel, were predicted by Conceptualization and Initiation/Perseveration subscales whereas the capacity to consent to a neurosurgical randomized clinical trial was predicted by the Memory subscale. Furthermore, the more lenient individual psychiatrists’ judgments were predicted by the Conceptualization subscale whereas the stricter psychiatrists’ judgments were predicted by the Memory subscale.
How experienced psychiatrists view Alzheimer’s patients’ capacity for consenting to research and for appointing a proxy may be related to the patients’ conceptualization and memory functioning. More explicit and standardized guidance on the role of short term memory in capacity determinations may be useful.
PMCID: PMC3382031  PMID: 23498384
decision-making capacity; neuropsychology; Alzheimer’s disease
9.  Is Late-Onset Schizophrenia a Subtype of Schizophrenia? 
Acta psychiatrica Scandinavica  2010;122(5):414-426.
To determine whether late-onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia.
Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia outpatients age > 40 (110 LOS, 744 early-onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning.
EOS and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. EOS and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS-LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness.
LOS should be considered a subtype of schizophrenia.
PMCID: PMC3939834  PMID: 20199491
Schizophrenia; aging; cognition; negative symptoms; quality of life; positive symptoms
10.  Using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Effort Index to Predict Treatment Group Attendance in Patients with Schizophrenia 
In a psychosocial treatment study, knowing which participants are likely to put forth adequate effort to maximize their treatment, such as attending group sessions and completing homework assignments, and knowing which participants need additional motivation prior-to engagement in treatment is a crucial component to treatment success. This study examined the ability of the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Effort Index (EI), a newly developed measure of suboptimal effort that is embedded within the RBANS, to predict group attendance in a sample of 128 middle-aged and older adults with schizophrenia. This study was the first to evaluate the EI with a schizophrenia sample. While the EI literature recommends a cutoff score of >3 to be considered indicative of poor effort, a cutoff of >4 was identified as the optimal cutoff for this sample. Receiver Operating Characteristics curve analyses were conducted to determine if the EI could predict participants who had high versus low attendance. Results indicated that the EI was successfully able to discriminate between group attendance, and this measure of effort appears to be most valuable as a tool to identify participants who will have high attendance. Interestingly, overall cognitive functioning and symptoms of psychopathology were not predictive of group attendance.
PMCID: PMC3568222  PMID: 23234753
Schizophrenia; Neuropsychology; RBANS; Symptom validity testing; Positive and Negative Symptoms; Receiver Operating Characteristics (ROC) curve
11.  Older Age is Associated with More Successful Aging: Role of Resilience and Depression 
The American journal of psychiatry  2013;170(2):188-196.
There is growing public health interest in understanding and promoting successful aging. While there has been some exciting empirical work on objective measures of physical health, relatively little published research combines physical, cognitive, and psychological assessments in large, randomly selected, community-based samples to assess self-rated successful aging (SRSA).
In this Successful AGing Evaluation (SAGE) study, we used a structured multi-cohort design to assess successful aging in 1,006 community-dwelling adults in San Diego County, aged 50–99 years, with over-sampling of people over 80. A modified version of random digit dialing was used to recruit subjects. Evaluations included a 25-minute phone interview followed by a comprehensive mail-in survey of physical, cognitive, and psychological domains, including SRSA (scaled from 1 [lowest] to 10 [highest]) and positive psychological traits.
In our sample with mean age of 77.3 years, the mean SRSA score was 8.2, and older age was associated with higher SRSA (R2 = 0.027), despite worsening physical and cognitive functioning. The best multiple regression model achieved, using all the potential correlates, accounted for 30% of variance in SRSA, and included resilience, depression, physical functioning, and age (entering the regression model in that order).
Resilience and depression had a significant association with SRSA with effect sizes comparable to that for physical health. While no causality can be inferred from cross-sectional data, increasing resilience and reducing depression might have as strong effects on successful aging as reducing physical disability, suggesting an important role for psychiatry in promoting successful aging.
PMCID: PMC3593664  PMID: 23223917
Aging; Resilience; Optimism; Depression; Cognition; Disability
12.  Characterizing Trajectories of Cognitive Functioning in Older Adults with Schizophrenia: Does Method Matter? 
Schizophrenia research  2012;143(1):90-96.
Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify etiology and even facilitate the identification of patient subtypes with common neuropathology and clinical course.
We compared trajectories (mean duration 3.5 years) of cognitive impairments in a sample of 201 community-dwelling schizophrenia (SCZ) patients (aged 40–100 years) with 67 healthy comparison (HC) subjects. We employed growth mixture models to discover subclasses with more homogenous between-subject variation in cognitive trajectories. Post hoc analyses determined factors associated with class membership and class-specific correlates of cognitive trajectories.
Three latent classes were indicated: Class 1 (85% HC and 50% SCZ) exhibited relatively high and stable trajectories of cognition, Class 2 (15% HC and 40% SCZ) exhibited lower, modestly declining trajectories, and Class 3 (10% SCZ) exhibited lower, more rapidly declining trajectories. Within the patient group, membership in Classes 2–3 was associated with worse negative symptoms and living in a board and care facility.
These results bridge the gap between schizophrenia studies demonstrating cognitive decline and those demonstrating stability. Moreover, a finer-grained characterization of heterogeneity in cognitive trajectories has practical implications for interventions and for case management of patients who show accelerated cognitive decline. Such a characterization requires study designs and analyses sensitive to between- and within-patient heterogeneity in outcomes.
PMCID: PMC3540183  PMID: 23218560
Late-Life Schizophrenia; Cognition; Trajectories; Heterogeneity; Growth Mixture Models
The aim of the present study was to explore the association between Parkinson’s disease (PD) clinical characteristics and cardiac autonomic control across sleep stages.
Frequency-domain heart rate variability (HRV) measures were estimated in 18 PD patients undergoing a night of polysomnography.
Significant relationships were found between PD severity and nocturnal HRV indices. The associations were restricted to rapid eye movement (R) sleep.
The progressive nocturnal cardiac autonomic impairment occurring with more severe PD can be subclinical emerging only during conditions requiring active modulation of physiological functions such as R-sleep.
PMCID: PMC3501606  PMID: 23141523
Heart rate variability; Parkinson’s disease; polysomnography; sleep
14.  Dimensions of Executive Functioning in Schizophrenia and Their Relationship With Processing Speed 
Schizophrenia Bulletin  2010;38(4):760-768.
Context: The nature of executive dysfunction in schizophrenia is nebulous, due to inconsistencies in conceptualizing and operationalizing the construct, and the broader question of whether schizophrenia is best characterized in terms of specific vs generalized cognitive deficits. The current study aimed to determine whether executive functions represent unitary vs diverse constructs in schizophrenia.
Methods: Participants included 145 community-dwelling individuals with schizophrenia. Executive functions were measured with the Delis-Kaplan Executive Functioning System (D-KEFS). We conducted an exploratory factor analysis (EFA) with principal axis factoring, as well as parallel analyses to examine the latent constructs underlying the D-KEFS tasks, a second EFA on weighted residuals of the D-KEFS tasks (after accounting for processing speed measured with the Digit Symbol task), and bivariate correlations to examine relationships between the D-KEFS components and relevant demographic and clinical variables, crystallized verbal knowledge, and functional capacity.
Results: EFA of the D-KEFS tasks yielded 2 factors (cognitive flexibility/timed tests and abstraction). EFA of the processing speed-weighted D-KEFS residuals also yielded 2 factors (cognitive flexibility and abstraction). Cognitive flexibility was negatively correlated with psychopathology. Better abstraction was associated with higher education, shorter illness duration, and better functional capacity. Both factors were positively correlated with crystallized verbal knowledge.
Conclusions: Executive functions in schizophrenia could be parsed into 2 partially related but separable subconstructs. Future efforts to elucidate functional outcomes as well as neurobiological underpinnings of schizophrenia may be facilitated by attending to the distinction between cognitive flexibility and abstraction.
PMCID: PMC3577045  PMID: 21163899
cognitive flexibility; abstraction; D-KEFS; factor analysis
Journal of the Neurological Sciences  2012;316(1-2):131-136.
The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinson’s disease (PD) and their impact on nocturnal sleep and daytime functioning.
Forty-five PD patients (mean age 68.5±8.7 years; 32 males) underwent one night of polysomnography (PSG). Clinical assessment and questionnaires evaluating sleep disturbance and quality of life (QoL) were completed. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI ≥15 (PLMS+) and PLMSI <15 (PLMS−).
There were 26 (57.8%) PD patients in the PLMS+ group and 19 (42.2%) patients in the PLMS− group. Subjective assessment revealed an association between PLMS+ status and greater PD symptom severity, more subjective sleep disturbance, and decreased QoL. All patients showed poor sleep, and no significant group differences were detected on PSG measures.
We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced QoL. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD.
PMCID: PMC3321115  PMID: 22277375
Dopaminergic treatment; Parkinson’s disease; periodic limb movements in sleep; polysomnography; quality of life; sleep disturbance
16.  Evaluation of Specific Executive Functioning Skills and the Processes Underlying Executive Control in Schizophrenia 
Schizophrenia is associated with executive dysfunction. Yet, the degree to which executive functions are impaired differentially, or above and beyond underlying basic cognitive processes is less clear. Participants included 145 matched pairs of individuals with schizophrenia (SCs) and normal comparison subjects (NCs). Executive functions were assessed with 10 tasks of the Delis-Kaplan Executive Function System (D-KEFS), in terms of “achievement scores” reflecting overall performance on the task. Five of these tasks (all measuring executive control) were further examined in terms of their basic component (e.g., processing speed) scores and contrast scores (reflecting residual higher order skills adjusted for basic component skills). Group differences were examined via multivariate analysis of variance. SCs had worse performance than NCs on all achievement scores, but the greatest SC-NC difference was that for the Trails Switching task. SCs also had worse performance than NCs on all basic component skills. Of the executive control tasks, only Trails Switching continued to be impaired after accounting for impairments in underlying basic component skills. Much of the impairment in executive functions in schizophrenia may reflect the underlying component skills rather than higher-order functions. However, the results from one task suggest that there might be additional impairment in some aspects of executive control.
PMCID: PMC3616491  PMID: 21062522
Cognition; Executive function; Schizoaffective disorder; Psychotic disorders; Trail Making Test; D-KEFS
17.  Undetected Cognitive Impairment and Decision-Making Capacity in Patients Receiving Hospice Care 
Cognitive dysfunction is common in patients with advanced, life-threatening illness and can be attributed to a variety of factors (e.g., advanced age, opiate medication). Such dysfunction likely affects decisional capacity, which is a crucial consideration as the end of life approaches and patients face multiple choices regarding treatment, family, and estate planning. This study examined the prevalence of cognitive impairment and its impact on decision-making abilities among hospice patients with neither a chart diagnosis of a cognitive disorder nor clinically apparent cognitive impairment (e.g., delirium, unresponsiveness).
110 participants receiving hospice services completed a one-hour neuropsychological battery, a measure of decisional capacity, and accompanying interviews.
In general, participants were mildly impaired on measures of verbal learning, verbal memory, and verbal fluency; 54% of the sample was classified as having significant, previously undetected cognitive impairment. These individuals performed significantly worse than the other participants on all neuropsychological and decisional capacity measures, with effect sizes ranging from medium to very large (0.43–2.70). A number of verbal abilities as well as global cognitive functioning significantly predicted decision-making capacity.
Despite an absence of documented or clinically obvious impairment, more than half of the sample had significant cognitive impairments. Assessment of cognition in hospice patients is warranted, including assessment of verbal abilities that may interfere with understanding or reasoning related to treatment decisions. Identification of patients at risk for impaired cognition and decision-making may lead to effective interventions to improve decision-making and honor the wishes of patients and families.
PMCID: PMC3309124  PMID: 22322907
dementia; delirium; hospice; neuropsychology; cognitive impairment; decision-making; palliative care
18.  Does Antidepressant Treatment Improve Cognition in Older People with Schizophrenia or Schizoaffective Disorder and Comorbid Subsyndromal Depression? 
Neuropsychobiology  2012;65(3):168-172.
Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. While treatment of depression in major depressive disorder may partially ameliorate cognitive deficits, the cognitive effects of antidepressant medications in patients with schizophrenia or schizoaffective disorder and SSD are unknown.
The goal of this study was to assess the impact of SSD and their treatment on cognition in participants with schizophrenia or schizoaffective disorder aged ≥40 years. Participants were randomly assigned to a flexible dose treatment with citalopram or placebo augmentation of their current medication for 12 weeks. An ANCOVA compared improvement in the cognitive composite scores, and a linear model determined the moderation of cognition on treatment effects based on the Hamilton Depression Rating Scale and the Calgary Depression Rating Scale scores between treatment groups.
There were no differences between the citalopram and placebo groups in changes in cognition. Baseline cognitive status did not moderate antidepressant treatment response.
Although there are other cogent reasons why SSD in schizophrenia warrant direct intervention, treatment does not substantially affect the level of cognitive functioning. Given the effects of cognitive deficits associated with schizophrenia on functional disability, there remains an ongoing need to identify effective means of directly ameliorating them.
PMCID: PMC3701889  PMID: 22456094
Schizophrenia; Citalopram; Cognition; Subsyndromal depression
19.  Divergent Trajectories of Physical, Cognitive, and Psychosocial Aging in Schizophrenia 
Schizophrenia Bulletin  2011;37(3):451-455.
Aging is not a uniform process. In the general population, there is a paradox of aging: age-associated decline in physical and some cognitive functions stands in contrast to an enhancement of subjective quality of life and psychosocial functioning. This paradox is even more striking in people with schizophrenia. Compared with the overall population, individuals with schizophrenia have accelerated physical aging (with increased and premature medical comorbidity and mortality) but a normal rate of cognitive aging, although with mild cognitive impairment starting from premorbid period and persisting throughout life. Remarkably, psychosocial function improves with age, with diminished psychotic symptoms, reduced psychiatric relapses requiring hospitalization and better self-management. Many older adults with schizophrenia successfully adapt to the illness, with increased use of positive coping techniques, enhanced self-esteem and increased social support. Although complete remission is uncommon, most individuals with schizophrenia experience significant improvement in their quality of well-being. Cohort effect and survivor bias may provide a partial explanation for this phenomenon. However, the improvement also may reflect some brain changes that are beneficial for the course of schizophrenia along with neuroplasticity of aging. The proposed hypothesis has several implications. As significant medical morbidity in schizophrenia takes years to develop, studies of changes in sensitive biomarkers of aging during the course of illness may point to new treatments aimed at normalizing the rate of biological aging in schizophrenia. At the same time, effective psychotherapeutic interventions can affect brain structure and function and produce lasting positive behavioral changes in aging adults with schizophrenia.
PMCID: PMC3080682  PMID: 21505111
psychosis; geriatric; quality of life; psychotherapy; neuropsychological; biomarkers
20.  Correlates of Spirituality in Older Women 
Aging & mental health  2011;15(1):97-102.
The role of spirituality in the context of mental health and successful aging is not well understood. In a sample of community-dwelling older women enrolled at the San Diego site of the Women's Health Initiative study, we examined the association between spirituality and a range of variables associated with successful cognitive and emotional aging, including optimism, resilience, depression, and health-related quality of life (HRQoL).
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women. It included multiple self-reported measures of positive psychological functioning (e.g., resilience, optimism,), as well as depression and HRQoL. Spirituality was measured using a 5-item self report scale constructed using two items from the Brief Multidimensional Measure of Religiosity/Spirituality and three items from Hoge's Intrinsic Religious Motivation Scale
Overall, 40% women reported regular attendance in organized religious practice, and 53% reported engaging in private spiritual practices. Several variables were significantly related to spirituality in bivariate associations; however, using model testing, spirituality was significantly associated only with higher resilience, lower income, lower education, and lower likelihood of being in a marital or committed relationship.
Our findings point to a role for spirituality in promoting resilience to stressors, possibly to a greater degree in persons with lower income and education level. Future longitudinal studies are needed to confirm these associations.
PMCID: PMC3017739  PMID: 20924814
Spirituality; religiosity; elderly; successful aging; resilience
21.  Decisional Capacity to Consent to Research in Schizophrenia: An Examination of Errors 
IRB  2011;33(4):1-9.
Despite substantial research on overall decision-making capacity (DMC) levels in schizophrenia, factors causing individuals to make errors during decision-making regarding research participation or treatment are relatively unknown.
We examined the responses of 84 middle-aged and older patients with schizophrenia or schizoaffective disorder on a structured DMC measure—the MacArthur Competence Assessment Tool for Clinical Research—to determine the frequency and apparent cause of patients’ errors.
Most errors were due to difficulty recalling the disclosed information (seen in 65.5% of patients), particularly the study’s procedures, potential risks/discomforts, and purpose. Errors attributable to concrete thinking, thought disorder or other psychotic symptoms, or perceived coercion were rarer.
Informed consent procedures might be improved for this population by providing information in a way that facilitates learning and memory, such as iterative disclosure of the information, corrective feedback, and emphasis of key points (e.g., the study’s purpose, procedures, and potential risks).
PMCID: PMC3245677  PMID: 21932481
22.  Exergames for Subsyndromal Depression in Older Adults: A Pilot Study of a Novel Intervention 
Subsyndromal depression (SSD) is several times more common than major depression in older adults, and is associated with significant negative health outcomes. Physical activity can improve depression, yet adherence is often poor. We assessed the feasibility, acceptability, and short-term efficacy and safety of a novel intervention using exergames (entertaining video games that combine game play with exercise) for SSD in older adults.
Community-dwelling older adults (N = 19, age 63–94) with SSD participated in a 12-week pilot study (with follow-up at 20 to 24 weeks) of Nintendo’s Wii Sports, with three 35-minute sessions a week.
86% of enrolled participants completed the 12-week intervention. There was a significant improvement in depressive symptoms, mental health-related quality of life, and cognitive performance, but not physical health-related quality of life. There were no major adverse events, and improvement in depression was maintained at follow-up.
The findings provide preliminary indication of the benefits of exergames in seniors with SSD. Randomized controlled trials of exergames for late-life SSD are warranted.
PMCID: PMC2827817  PMID: 20173423
Physical activity; Aging; Videogames; Depression; Quality of life; Cognition
23.  Multimedia Consent for Research in People With Schizophrenia and Normal Subjects: a Randomized Controlled Trial 
Schizophrenia Bulletin  2008;35(4):719-729.
Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.
PMCID: PMC2696362  PMID: 18245061
bioethics; mental competency; informed consent; multimedia learning; cognition disorders; schizophrenia
24.  Worth the Risk? Relationship of Incentives to Risk and Benefit Perceptions and Willingness to Participate in Schizophrenia Research 
Schizophrenia Bulletin  2008;35(4):730-737.
Objective: Providing incentives for research participation is widely practiced but minimally studied. In schizophrenia research, questions about capacity to consent and potential vulnerability may raise concerns when offering incentives for participation. Despite empirical attention focused on consent and decision-making capacity in schizophrenia, the issue of incentives has been essentially ignored. We examined willingness to participate in research, in relation to perceived risks and benefits, among people with schizophrenia and schizoaffective disorder. Method: Forty-six people with schizophrenia or schizoaffective disorder rated perceived risks and benefits of 5 hypothetical research vignettes. They also indicated whether they would be willing to participate at each of 5 incentive levels (including no compensation). Cognition was assessed with Mattis Dementia Rating Scale. Results: Ratings of risk and potential personal benefit were inversely correlated. For all scenarios, significant correlations were found between perceived risk and willingness to participate for greater compensation. Conversely, lower perceived likelihood of benefit was associated with a higher compensation threshold for participation in each scenario. Even at the highest proffered payment level for each scenario, however, a substantial proportion of respondents were not willing to participate. Risk assessment and willingness to participate (at all levels of compensation) were not associated with demographic variables or cognitive status. Conclusions: Determining whether incentives impede voluntarism remains an important task for empirical ethics research. Assessing potential research participants’ understanding and perceptions of risks, benefits, and alternatives to participation will help ensure that informed consent fulfills its mission—embodying the ethical principle of respect for persons.
PMCID: PMC2696364  PMID: 18281293
ethics; informed consent; research participation; incentives; risk perception; voluntarism
25.  Cognitive Effects of Treating Obstructive Sleep Apnea in Alzheimer's Disease: A Randomized Controlled Study 
To examine whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients with Alzheimer's disease (AD) would result in improved cognitive function.
Randomized double-blind placebo-controlled trial. Participants were randomized to either therapeutic CPAP for six weeks or placebo CPAP for three weeks followed by therapeutic CPAP for three weeks.
General clinical research center
52 men and women with mild-moderate AD and OSA
Continuous positive airway pressure
A complete neuropsychological test battery was administered before treatment, at three and at six-weeks.
A comparison of subjects randomized to 3 weeks of therapeutic versus placebo CPAP suggested no significant improvements in cognition. A comparison of pre- versus post-treatment neuropsychological test scores after 3 weeks of therapeutic CPAP in both groups showed a significant improvement in cognition. The study was underpowered to make definitive statements about improvements within specific cognitive constructs. However, exploratory post-hoc examination of change scores for individual tests suggested improvements in episodic verbal learning and memory and some aspects of executive functioning such as cognitive flexibility, and mental processing speed.
OSA may aggravate cognitive dysfunction in dementia and thus may be a reversible cause of cognitive loss in AD patients. OSA treatment seems to improve some of the cognitive functioning. Clinicians who care for AD patients should consider implementing CPAP treatment when OSA is present.
PMCID: PMC2585146  PMID: 18795985
dementia; Alzheimer's disease; obstructive sleep apnea; CPAP; cognitive impairment

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