ROCHETTE, AMBER DENAE, M.A. MAY 2017 PSYCHOLOGICAL SCIENCES THE RELATIONSHIP BETWEEN CHA DS -VASc STROKE RISK SCORES AND 2 2 COGNITIVE FUNCTION PRE- AND POST-BARIATRIC SURGERY Thesis Advisor: John Gunstad Severe obesity is associated with elevated risk for poor neurocognitive outcomes. The mechanisms underlying this association have not yet been fully elucidated, but cerebrovascular pathology resulting from obesity and its associated vascular risk factors has been identified as a likely contributor. The CHA DS -VASc is a clinical composite score used to assess risk for 2 2 vascular events and has been used to estimate severity of cerebrovascular pathology. Past research shows associations between higher scores on the CHA DS -VASc and poorer cognitive 2 2 function in persons with atrial fibrillation and advanced heart failure. However, no study has examined the predictive validity of CHA DS -VASc in persons with severe obesity. The current 2 2 study examined the relationship between the CHA DS -VASc and cognitive function before and 2 2 after bariatric surgery in a sample of individuals with severe obesity. Data from 87 bariatric surgery patients were extracted from a larger parent project. Cognitive function was assessed at baseline and 12 months following bariatric surgery. Self-report questionnaires were completed at the baseline visit to gain medical and demographic information. It was hypothesized that CHA DS -VASc scores would predict cognitive function in individuals with severe obesity prior 2 2 to bariatric surgery, as well as improvements in cognitive function 12 months post-surgery. Additionally, the CHA DS -VASc was hypothesized to predict percent weight loss. Analyses 2 2 revealed significant improvements in cognitive function from pre- to post-surgery in domains of memory, attention, and executive function. No significant associations were observed between the CHA DS -VASc and cognitive function at baseline and the stroke risk score did not predict 2 2 the cognitive improvements seen in memory, executive function, or attention post-surgery. However, an association was found between CHA DS -VASc scores and percent weight loss 12 2 2 months post-surgery, such that higher CHA DS -VASc scores were negatively associated with 2 2 percent weight loss. Future work is needed to clarify these findings and determine whether the CHA DS -VASc may have clinical utility in this population. 2 2 THE RELATIONSHIP BETWEEN CHA DS -VASc STROKE RISK SCORES AND 2 2 COGNITIVE FUNCTION PRE- AND POST-BARIATRIC SURGERY A thesis submitted to Kent State University in partial fulfillment of the requirements for the degree of Master of Arts By Amber Rochette May 2017 © Copyright All rights reserved Except for previously published materials Thesis written by Amber Denae Rochette B.A., University of North Carolina at Chapel Hill, 2011 M.A., Kent State University, 2017 Approved by John Gunstad , Advisor Maria S. Zaragoza , Chair, Department of Psychological Sciences James L. Blank_____________________, Dean, College of Arts and Sciences TABLE OF CONTENTS.................................................................................................................v LIST OF TABLES..........................................................................................................................vi ACKNOWLEDGEMENTS...........................................................................................................vii CHAPTERS I. Introduction.............................................................................................................1 II. Methods..................................................................................................................14 III. Results....................................................................................................................21 IV. Discussion..............................................................................................................26 REFERENCES............................................................................................................................. 33 v LIST OF TABLES Table 1. CHA DS -VASc Point System 2 2 (Table adapted from Lip et al., 2010)……........................................................................48 Table 2. Sample Demographic and Medical Characteristics at Baseline (n = 87)...............................................................................................................................49 Table 3. Comparison of Baseline and 12-Month T-Scores for Cognitive Test Performance ......................................................................................................................50 Table 4. Regression Model Examining the Predictive Validity of CHA DS -VASc on Cognitive 2 2 Function at Baseline...........................................................................................................52 Table 5. Regression Model Examining the Predictive Validity of CHA DS -VASc on Cognitive 2 2 Function at 12-Months Post-Surgery..............................................................................53 Table 6: Regression Model Examining the Predictive Validity of CHA DS -VASc on Percent 2 2 Weight Loss at 12-Months Post-Surgery………………………………………………54 vi Acknowledgements I would like to acknowledge the many individuals who saw to the completion of this thesis project and refinement of this document. I would first like to thank my advisor, Dr. John Gunstad, for providing me with mentorship and support and for challenging me to think critically through all stages of this project. I am also grateful for the support and feedback I received from my committee: Dr. Mary Beth Spitznagel, Dr. Amy Sato, and Dr. Doug Delahanty. Lastly, I would like to thank my wonderful cohort for their support and feedback throughout this process. vii Introduction The number and proportion of adults with obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, have risen dramatically over the past several decades and continue to rise at an alarming rate (Ng et al., 2014). Globally, the number of individuals with obesity was estimated at 396 million (9.8% of the population) in 2005 and this number is estimated to increase to as high as 1.12 billion (20% of the population) by 2030 (Kelly, Yang, Chen, Reynolds, & He, 2008). The prevalence is even higher in the United States, as an estimated 29% of the population was obese in 2005 and this number is projected to increase to 50% by 2030 (Kelly et al., 2008; Finkelstein et al., 2012). Treatment for obesity consumes approximately 10% of the national health care budget and costs are expected to double over the next decade as prevalence rates of obesity continue to increase (Andreyeva, Sturm, & Ringel, 2004; Wang, Beydoun, Liang, Caballero, & Kumanyika, 2008). Public Health Implications of Obesity The growing prevalence of obesity has significant consequences at the individual and societal level. Together, obesity and its medical comorbidities significantly diminish quality of life and increase mortality (Vallis, 2016; Peeters et al., 2003). As individuals with obesity in midlife enter older adulthood, they develop limitations in activities of daily living 5 to 6 years earlier than their normal weight peers (Peeters, Bonneux, Nusselder, De Laet, & Barendregt, 2004). BMI has also been shown to predict declines in perceived health and mobility, even after controlling for presence and severity of comorbid conditions (Damush, Stump, & Clark, 2002). Research from the Framingham Heart Study found that midlife obesity reduces life duration by 6 1 to 7 years (Peeters et al., 2003). In 2000, excess weight was the second leading modifiable cause of death, accounting for approximately 17% of deaths in the United States, and researchers predict that excess weight will soon overtake tobacco as the leading modifiable cause of death if its increasing prevalence is not abated (Mokdad, Marks, Stroup, & Gerberding, 2004). Some research indicates that without successful intervention, obesity may lead to the first decline in human life expectancy in centuries (Olshansky et al., 2005). Obesity is associated with a host of comorbid medical conditions. Obesity is an independent risk factor for cardiovascular disease (CVD) and is associated with many vascular risk factors, including hypertension, type 2 diabetes mellitus, and dyslipidemia (Poirer et al., 2006; Ogden, Yanovski, Carroll, & Flegal, 2007). Other conditions commonly associated with obesity include sleep apnea, osteoarthritis, gastroesophageal reflux disease, and certain cancers (Must et al., 1999; Jacobson et al., 2006; Deng, Lyon, Bergin, Caligiuri, & Hsueh, 2016). In addition to these many medical conditions, research demonstrates that obesity is also an independent risk factor for poor neurological outcomes. Obesity is associated with an increased risk for stroke, as a meta-analysis of 25 prospective studies found that individuals with obesity have a 64% higher likelihood of stroke compared to their normal weight peers (Strazzullo et al., 2010). Similarly, longitudinal research by Whitmer and colleagues followed individuals for approximately 36 years and found that individuals with obesity in midlife were at a 3 times greater risk of developing Alzheimer’s disease and a 5 times greater risk of developing vascular dementia (Whitmer, Gunderson, Quesenberry, Zhou, & Yaffe, 2007). There is also a growing body of research demonstrating cognitive dysfunction in persons with obesity across the adult lifespan prior to the onset of these neurological conditions. A systematic review of the literature by Prickett and colleagues revealed consistent findings of 2 frontal systems dysfunction in adults with obesity, as evidenced by decreased performance on tasks of executive function and processing speed (Prickett, Brennan, & Stolwyk, 2015). Further, deficits in learning and memory are found in this population relative to controls, independent of age and other comorbidities (Cheke, Simons, & Clayton, 2016; Gunstad, Paul, Cohen, Tate, & Gordon, 2006). Findings of adverse neurocognitive outcomes in persons with obesity are further supported by imaging studies. Inverse associations are noted between BMI and total brain volume, as well as gray matter volume in frontal and temporal brain regions (Taki et al., 2008; Gustafson, Lissner, Bengtsson, Bjorkelund, & Skoog, 2004; Gunstad et al., 2008; Pannacciulli et al., 2006). These findings exist independent of age and associated comorbidities, suggesting an independent influence of obesity on brain structure (Gunstad et al., 2008). Longitudinal work also links obesity with greater hippocampal atrophy (Driscoll et al., 2012; Debette et al., 2011). Structural alterations further extend to white matter, with compromises in white matter integrity found globally in the brains of individuals with higher BMIs (Verstynen et al., 2012). Functional brain alterations are also noted in this population, as individuals with higher BMI demonstrate reduced metabolic activity in the prefrontal cortex and cingulate gyrus and decreased regional blood flow in the prefrontal cortex (Volkow et al., 2009; Willeumier, Taylor, & Amen, 2011). Public Health Implications of Severe Obesity While it is informative to look at the health consequences of obesity, it obscures important variations across level of obesity severity. Risk for poor health outcomes increases exponentially with increasing BMI (Hensrud & Klein, 2006). A BMI of 30 to 34.9 is categorized as Class I Obesity and confers high relative risk of developing comorbidities, such as diabetes, hypertension, and cardiovascular disease. A BMI of 35 to 39.9 is labeled Class II 3