Objectives: Older adults with chronic schizophrenia are at greater risk for functional disability and poorer health outcomes than those without serious mental illness. This population makes up 0.6% to 1% of the elderly population in the US and is projected to number approximately 15 million by 2030. The symptoms of schizophrenia can be disabling for individuals, significantly reducing their quality of life. Often, the negative symptoms are the most resistant to treatment and are considered a marker of illness severity, although challenging to measure objectively. Biomarkers can provide an objective indicator of health status. Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker for schizophrenia and may serve as an indicator of illness severity. Materials and methods: A cross-sectional study with 30 older adults with chronic schizophrenia. Participants were assessed on serum levels of BDNF and psychiatric symptoms (Positive and Negative Syndrome Scale; PANSS). Pearson’s bivariate correlations (two-tailed) and linear regression models were used. Results: Average serum levels of BDNF were 24.4 ng/mL (SD = 6.0). A significant positive association (p < .05) was found between higher serum levels of BDNF and greater severity for the negative symptom items that included passive, apathetic, social withdrawal, and emotional withdrawal. In multivariate analyses, the association remained significant. Conclusions: Although the association between BDNF and negative symptoms was not in the expected direction, the data corroborate findings from previous work in patients with schizophrenia. It is possible that higher serum levels of BDNF reflect compensatory mechanisms resulting from neurodevelopmental dysfunction.

Background: Since the onset of the HIV epidemic, antiretroviral therapy (ART) has lengthened the lives of people living with HIV (PLWH). More than half of the population of PLWH are 50 years and older, and as the aging population of PLWH expands it is important to consider the environmental, socio-structural, and biological factors and pathways that impact aging with HIV (Centers for Disease Control and Prevention [CDC], 2018). It is estimated that about a third to one half of HIV-seropositive individuals have some degree of cognitive impairment (Heaton et al., 2010), though prevalence may be lower in populations with sustained viral suppression (V. Valcour, personal communication, December 2018). Studies show that various measures of loneliness and social isolation are associated with risk for cognitive impairment and dementias among the general population (Kuiper et al., 2015, 2019). Literature also indicates that, on average, PLWH experience more loneliness and social isolation than HIV-seronegative individuals (Greene et al., 2018; Grov et al., 2010; Poindexter & Shippy, 2008). In addition to the environmental and social factors that impact risk for cognitive impairment among PLWH, the study of inflammatory processes and biomarkers—and whether these are important for the development of HAND—is an important area of current research (Office of AIDS Research [OAR] Working Group on HIV and Aging, 2012). Current evidence demonstrates an overall increased risk of morbidity and mortality in HIV-positive individuals whose CD4/CD8 ratio fails to normalize above 1.0 (Mussini et al., 2015; Serrano-Villar et al., 2013, 2014). Additionally, a small number of studies show that inverted CD4/CD8 ratio is associated with the development of neurocognitive disorders (Correa et al., 2014; Grauer et al., 2015; Rawson et al., 2015; Vassallo et al., 2017). Problem Statement: The central hypotheses motivating this dissertation research is that loneliness and social isolation represent two distinct and uniquely important factors in the risk of cognitive impairment among people aging with HIV, and that CD4/CD8 ratio is an endophenotype that may help elucidate the pathways by which physical health, mental health, and environmental factors impact cognitive impairment among PLWH. Chapter 2: The 2nd chapter of this dissertation systematically examined the current body of quantitative literature about social support and loneliness and cognitive impairment among PLWH. We used meta-analysis to summarize the association of these variables and used meta-regression to identify moderating variables in N=11 studies. Among the 11 studies reviewed, many were limited by the use of un-validated measures of loneliness and/or social support as well as heterogeneous measures of cognitive symptoms and cognitive performance. The meta-analysis (n=10) showed a positive association between social isolation or loneliness and cognitive impairment. Though there was moderate heterogeneity among the studies analyzed, there was not substantial publication bias. Meta-regression showed moderation of the association by study quality, older age (≥55 years), and study country but not by sample mean CD4 cell count. This paper highlights knowledge gaps in the current body of research and reflects distinctions between performance-based and self-reported measures of cognitive impairment as well as various dimensions of social connectedness. Chapter 3: Building on the knowledge gaps identified in the second dissertation chapter, the 3rd chapter of this dissertation examined the association of both loneliness and social isolation with performance based cognitive impairment and subjective cognitive complaints in a sample of older adults living with HIV and confirmed HIV-Associated Neurocognitive Disorders (HAND). We performed a cross-sectional, secondary data analysis in a cohort of older adults living with HIV recruited at the Memory and Aging Center (N=171). This paper revealed that loneliness was correlated with mental health variables (depression, anxiety, and perceived stress) while social isolation was correlated with other marginalized conditions and socioeconomic factors (lower years of education, history of Hepatitis C (HCV), history of a substance use disorder, and Black/African American race, and area-level socioeconomic environment). This paper also showed that social isolation, but not loneliness, was associated with higher odds of impairment in two cognitive domains (Attention and Executive function [ATT] and Speed of Processing [SPD]). We concluded that social isolation may be conceptualized as a pathway of embodiment, reflecting experiences of marginality that could impact risk of HAND. Chapter 4: The 4th chapter of the dissertation used an exploratory, cross-sectional secondary analysis of the the Hawaii Aging with HIV Cardiovascular Study (HAHCS) cohort-Public Data Set. We aimed to examine the relationships between CD4/CD8 and biomarkers of inflammation among middle-aged and older adults living with HIV (N=103). This study revealed that the lowest tertile of CD4/CD8 ratio (Median: 0.346, range 0.123-0.501) was associated with a higher inflammation profile and higher concentration of mature monocytes in the blood. In elucidating the CD4/CD8 cell ratio among PLWH, this paper contributes to the body of evidence that suggests a link between CD4/CD8 ratio and established risk factors for HAND among middle-aged and older adults with HIV. Chapter 5: The 5th chapter of the dissertation was a longitudinal study of the Women’s Interagency Health Study (WIHS) public data set to examine the intra-individual variability of the CD4/CD8 ratio over 10 years as well as clinical and sociodemographic correlates of CD4/CD8 ratio among women living with HIV (n=1462). This study revealed that, over 10 years, the CD4/CD8 ratio remained relatively stable. Over time, decreased CD4/CD8 ratio was associated with higher age, detectable viral load, and sub-optimal ART adherence. We then examined associations of clinical and sociodemographic with “inverted” CD4/CD8 ratio (≤ 1.0 versus >1.0) and “low” CD4/CD8 ratio (≤ 0.70 versus >0.70). This paper revealed that inverted and low CD4/CD8 ratio were both associated with detectable viral load and fewer years of educational attainment. Because much of the WIHS sample had a CD4/CD8 ratio that was below 0.50, in addition to the findings from chapter 4 that indicate inflammation is association with the lowest tertile of CD4/CD8 ratio (0.123-0.501), we subsequently performed a follow-up analysis to examine variables associated with “very low” CD4/CD8 ratio (≤0.50 versus >0.50). We found that very low CD4/CD8 ratio was associated with older age, detectable viral load, past/current Hepatitis C, white racial group, and lower educational attainment. Overall, the findings from this paper show that CD4/CD8 ratio was relatively stable over time, but was significantly influenced by age, viral load, and adherence to ART medications. We also found that inverted, low, and very CD4/CD8 ratio were all associated with fewer years of education. In linking CD4/CD8 ratio to lower educational attainment, our study implicates immune function as a pathway by which root causes and social determinants of health (SDOH) may impact risk of cognitive impairment among women with HIV.

Introduction: The number of older adults with a serious mental illness (SMI) is predicted to more than double to 15 million by the year 2030. Older adults with SMI tend to have multiple medical problems in addition to serious psychiatric symptoms. Although the concept of healthy aging in SMI is gaining further attention, it has not historically been a common framework for mental illness treatment, rehabilitation, or recovery. Healthy aging includes the promotion of interconnected aspects of physical, emotional, and psychological wellbeing. The burgeoning field of inquiry about the effects of exergames on physical health and psychological wellbeing in older adults has found that exergames are safe, effective, enjoyable, and may improve depressive symptoms. Methods: We conducted qualitative interviews with 15 older adults with SMI who participated in a 10-week group exergame program. Data were collected and analyzed using grounded theory methodology within a symbolic interactionist framework. Results: Three important and interrelated concepts emerged from the data: Competence, Social Connectedness, and Energy. Play and playfulness became the vehicle for interacting social processes to take place. In the context of play, the participants experienced themselves in relationship to one another, gave and received empathy and positive social contact, engaged in social attunement, and became motivated to take risks and to face cognitive and physical challenges. In social environments where higher playfulness was cultivated, participants were more willing to engage in competition and described a sense of subjective wellbeing. Play and playfulness is strongly associated with increased social connectedness, which in turn supports intrinsic motivation, self-determination, and fulfills certain innate psychological needs that support wellness, growth, and recovery. Conclusion: Social disconnectedness and perceived isolation among older adults with SMI is complex and involves factors including organic psychopathology, physical effects of medications and/or other substances, medical co-morbidity, disability, and social stigma. Group play exergames for older adults with SMI may have the potential to promote recovery and healthy aging by increasing social integration, improving self-efficacy, and promoting physical health through exercise.

Background: Over 4 million adults are admitted annually to intensive care units (ICU) in the US. Critically ill patients experience significant symptom burden including high rates of pain, anxiety, delirium, restlessness, dyspnea, confusion, sleep disorders, loneliness, depression, and fear. Advanced respiratory support with mechanical ventilation (MV) is the most common intervention used in critical care and is an independent risk factor for each of these co-occurring symptoms. Medications are of limited effectiveness for the management of many symptoms and also confer increased morbidity including worsening delirium, increased length of stay and the development of long-term psychological and cognitive problems. To mitigate these risks, guidelines for symptom management in the ICU include recommendations for the use of non-pharmacologic therapies such as music-based interventions. Purpose: The purpose of this dissertation study is to analyze and synthesize existing literature that measures outcomes of recorded music listening interventions (RMLIs) for the management of common symptoms in critically ill adults during MV, and to describe the effects of listening to recorded music during critical care hospitalization. Methods: This dissertation presents three manuscripts. The first is a systematic review summarizing the state of the evidence that examines RMLIs to manage common symptoms experienced by critically ill adults during MV using the 2009 PRISMA guidelines. The inclusion criteria were experimental and quasi-experimental designed studies published between January 1, 1998, and March 20, 2022. The quality of available evidence was evaluated using the Evidence Project Risk of bias tool. The second study is a grounded theory analysis of patients’ perceptions of the effects of listening to self-selected music on symptom experience during MV and critical care hospitalization. The third study examines the effects of a personally selected RMLI on ventilator-derived breathing measures of rate, depth and pattern during MV. Both prospective studies were conducted in the Surgical and Neurosurgical ICUs of a single, academic, urban, level-one trauma center and safety net hospital in San Francisco, California between August 2020, and November 2021. Results: The results of the systematic review confirm that RMLIs are effective for the treatment of anxiety and pain and also identified other common symptoms such as agitation, that may be moderated by RMLIs in adults during MV. Most studies used investigator-selected music or restricted music to a limited selection of slow tempo recordings. The broad scope of the review and heterogeneity of outcome measures confounded synthesis of the results and precluded summative recommendations for RMLIs for symptom management but highlighted important literature gaps. Specifically, few studies measured the effect of RMLIs on common symptoms such as dyspnea, confusion, delirium, sleep, loneliness, and general distress. Physiologic signs did not vary with RMLI, underscoring the lack of reliable objective instruments that measure the effects of RMLI in patients unable to self-report. Results of the qualitative study show that listening to personally selected recorded music may be beneficial for cognitive and psychological recovery in ICU. Analysis of 14 semi-structured interviews, notes, and observations revealed 6 uses of personally selected music listening in ICU: 1) Restoring consciousness; 2) Maintaining cognition; 3) Humanizing the hospital experience; 4) Providing a source of connection; 5) Improving psychological wellbeing; and 6) Resolving the problems of silence. Recorded music was rarely used to address pain or anxiety. Instead, participants reported the use of recorded music listening to address complex psychological experiences of loneliness, fear, de-situation, confusion, intrusive thoughts, threats to identity and loss of control through the use of music related memories and distraction. Listening to self-selected music provided a sense of self and a method to process trauma and grief. Additional benefits of listening to recorded music included feeling joy, pleasure, hope, resilience, and a sense of normalcy. Participants identified an aversion to being sedated as well as feelings of abandonment and restraint associated with silence. In the quantitative analysis, breathing measures theoretically associated with relaxation did not vary as hypothesized with an RMLI during both machine-controlled ventilation and spontaneous breathing modalities. In this pilot study of 16 critically ill adults during MV, analysis of breath-by-breath data did not demonstrate an effect of RMLIs on respiratory rate (breaths per minute), breath depth (tidal volume in liters or maximum pressure associated with fixed volume breaths), nor breath pattern (liters of breath per minute, breaths per liter per minute, inspiratory flow, and other indirect measures of work of breathing). The null results in this pilot were likely related to the magnitude of the variance within the small sample, high incidence of delirium, and the heterogeneity of the music selections in the intervention. Use of a noninvasive pulmonary mechanics monitor facilitated the collection of objective, rich, continuous data and is a feasible instrument that adds to the rigor of the findings. Conclusions: The morbidity associated with the symptoms experienced during MV speak to the imperative to expand the access to and use of non-pharmacologic interventions for adults during critical care hospitalization. Listening to preferred, personally selected music represents a safe, widely acceptable, equitable intervention that is likely to be of benefit for the management of common psychological and cognitive symptoms not amenable to traditional medical interventions. Future studies that use validated instruments that address clinically meaningful outcomes will provide scientific justification for the use of RMLIs and contribute to the understanding of the mechanism of action of RMLIs.

Objectives: Older adults with serious mental illness (SMI) are more likely to have high body mass index (BMI) and chronic conditions such as cardiovascular disease and diabetes. A sedentary lifestyle which may be attributed to pharmacologic side effects and the symptoms of mental illness, has been difficult to treat. Patients experiencing negative symptoms (e.g., apathy, anhedonia) may be more likely to exercise in a group setting with activities that are designed to stimulate the mind and encourage engagement. “Exergames” or exercise-based videogames, are an interactive and stimulating method to provide aerobic activities. Exercise has also been shown to reduce the symptoms of depression. The purpose of this study is to evaluate the impact of exergames on depressive and negative symptoms in older adults with SMI. Materials and Methods: A single-group pretest posttest study was conducted with 52 older adults diagnosed with SMI. Participants engaged in group exergame activities for 50-minute sessions three times a week for 10 weeks. The Patient Reported Outcome Measurement Information System or PROMIS, and the Scale for the Assessment of Negative Symptoms or SANS, were conducted at enrollment, 5 weeks, and 10 weeks. Results: Participants achieved statistically significant reductions in self-reported depressive symptoms (-0.83, LL -1.46, UL -0.12) and observed negative symptoms (-5.29, LL -7.64, UL -2.94) over a 10-week period. Conclusions: Our results suggest utilization of exergames as an adjunct treatment can be an effective, engaging, and cost-efficient method to reducing depressive and negative symptoms in older adults with SMI. Future studies should evaluate exergame effects with a larger sample.

The portion of older adults with schizophrenia is growing and their physical health status is poor. Many factors contribute to poor physical health including unhealthy lifestyles, poorly managed chronic diseases, and socio-demographic factors. The purpose of this dissertation was to explore how older adults with schizophrenia understand their physical health

A quantitative secondary data analysis was conducted based on a randomized lifestyle intervention program for older persons with schizophrenia or schizoaffective disorder and diabetes mellitus recruited from board-and-care facilities and day treatment programs to explore the relationship between the symptoms of schizophrenia experienced and response to the intervention. The qualitative aspect was conducted using a grounded theory approach to guide interviews with 28 older adults with schizophrenia or schizoaffective disorder recruited from three mental health facilities to explore the individual understanding of physical health.

The quantitative study revealed a significant condition by symptom interaction for diabetes knowledge. The difference between change in knowledge for intervention and control groups depends on prevalence and severity of total, negative, and general symptoms. There was not a significant condition by positive symptom interaction for diabetes knowledge. A significant main effect was found between total, negative, positive, and general symptoms in the total sample for diabetes self-efficacy. Higher prevalence and severity of symptoms was negatively associated with improvement in diabetes self-efficacy.

The qualitative data revealed that while discussing conceptions of physical health, participants spoke about a sense of belonging as one of the key factors supporting feeling healthy. A sense of belonging could be derived from a sense of connection with others, a physical place, social relationships, and a sense of meaning and purpose. Also, the concept of trust between participants, health care providers, and the health care system emerged as a dynamic process that was built with factors of respect, caring, advocacy, and consistency and eroded through factors of disrespect, not being heard, lack of time, provider inaction, and stigmatization.

The symptoms and experience of schizophrenia, the health care system, and health care providers are critical factors to consider in the development of targeted interventions to improve the physical health of this population.

Family caregivers of persons with dementia are at increased risk for adverse health outcomes than their peers not in a caregiving role. Persistent heterogeneity in the literature focused on outcomes in this population complicates efforts at identifying who is at greatest risk and for what outcomes as well as avenues for personalizing their care. The purpose of this dissertation was to explore factors contributing to the experiences and health outcomes of family caregivers (FCG) of persons with dementia (PWD). The overarching goal of this dissertation was to move the science as well as clinical practice forward in providing individualized care to our family caregivers of persons with dementia. This dissertation sought to achieve this goal through triangulating data from both quantitative and qualitative sources. A systematic review of the literature was conducted with a meta-analysis of the included studies’ findings related to assessing personality traits (PT) as predictors of outcomes in the FCG of PWD. A quantitative secondary analysis was then conducted based on a self-report measure of PT in a sample of FCG of PWD. A novel approach using latent profile analysis was employed in this study for purposes of exploring how group membership into classes of PT profiles was associated with health outcomes in this population of FCG. The qualitative aspect explored theory development around a sub-group of FCG using a grounded theory approach to guide interviews and participant observations with 15 spouses of persons with an early-age of onset dementia (EOD) syndrome. The systematic review with meta-analysis evaluated the strength of the current evidence supporting the assessment of PT (as defined by the Five Factor Model of Personality) of the FCG of PWD as significant predictors of these caregivers’ health outcomes, explaining some of the persistent heterogeneity observed. Only the dimensions of Neuroticism and Extraversion showed the greatest utility as reliable predictors through this review process, however. The meta-analyses of these data from the systematic review revealed statistically significant associations between Neuroticism and burden (pooled-r = .304), Neuroticism and depression (pooled-r = .593), and Extraversion and burden (pooled-r = -.233).The quantitative study revealed a statistically significant difference between class membership and life satisfaction. Two classes (i.e., profiles) were identified through methods of latent class analysis that best fit the data. Membership in the “Higher Resilience” (HR) class was associated with higher self-reported measures of “global cognitive judgement” of personal satisfaction with life than membership in the “Lower Resilience” (LR) class. Membership in the HR class was also associated with higher self-reported measures of bodily pain and role limitation due to emotional problems as assessed by the SF-36 health-related quality of life (HRQoL) instrument. No significant differences between the HR and LR classes were identified in participant or patient characteristics or in the FCG outcomes of perceived burden, distress, depression, anxiety level, or the HRQoL subscales of physical role limitations. The qualitative data revealed an underlying psychosocial process of a step-wise progression in role identity in spouses of persons with an EOD syndrome. A shift was described in how the well-spouse self-identified in the situation from that of “spouse” to that of “caregiver”. These “step-downs” in the transition were interpreted as representing “moments of significance” in the PWEOD’s continuous decline that held special meaning to the respective well-spouse and challenged them to take action in order to resolve resulting incongruencies to what it meant to them to be a spouse. The conditions of the situation (i.e., changes in the marital partnership and the interpersonal relationship between the dyads) carried unique aspects for this sub-group of FCG primarily due to the relatively young life stage at which this has occurred and the repercussions on their family and social life as well as financially. Inter-individual factors (i.e., personality traits) as well as understandings of the unique situations of sub-groups of caregivers (i.e., spouses of PWEOD) are factors which contribute significantly to the experiences as well as to health outcomes of FCG of PWD. They are critical factors to consider in the development of tailored interventions aimed at improving the health outcomes of this population of FCG.

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