Graduate Thesis Or Dissertation


Phenotypes of Cardiovascular Damage and Cognitive Decline Public Deposited

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  • Cognitive impairment can severely impact quality of life, and can place added strain on family and caregivers.¹⁻³ Moreover, cognitive decline has been shown to proceed to more serious conditions including Alzheimer’s disease and dementia,⁴⁻⁶ making it critical to intervene on risk factors. In addition to traditional risk factors for cognitive decline, including level of education, cardiovascular disease (CVD), total cholesterol and diabetes among others,⁷⁻⁸ subclinical cardiovascular disease (SCVD), and markers of cardiovascular damage have been associated with reduced cognitive function in older adults.⁹⁻¹⁰ This relationship has been observed even in the absence of clinical cardiovascular disease.⁶⁻⁷ In addition, recent evidence has shown that older adults have a range of cardiovascular damage, and that coronary and peripheral vascular disease is heterogeneous.¹³⁻¹⁵ These reasons indicate an essential need to re-examine the relationship between cardiovascular damage and cognitive function. Although the relationship between individual and composite scores of cardiovascular damage with cognitive impairment is well established, there is less known about how the interrelationship of these indicators are associated with trajectories of cognitive decline. While past studies have greatly improved our understanding of the relationship between cardiovascular damage and cognitive function, these studies have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of pathophysiologic changes that underlie cognitive impairment. Furthermore, the association between phenotypes of cardiovascular damage and trajectories of cognitive decline may give rise to more informed clinical interventions. This dissertation has two overarching goals: (i) To cluster participants into phenotypes based on the interrelationship between indicators of cardiovascular damage; and (ii) To explore which phenotypes are at greatest risk for cognitive decline and incident dementia with the intention of improving clinical interventions and igniting future research in the field of cardiovascular and cognitive aging. In addition, because of the inconsistency in results relating to sex differences with cognitive function, and to further distinguish the pathways between cardiovascular damage and cognitive function, effect modification by sex, and mediation by CVD and depression was also examined. First, results yielded 5 phenotype classes: healthy, cardiac, inflammatory, multisystem morbidity and vascular, and that the distinction of classes differed between sex. These findings demonstrate the multidimensionality of cardiovascular damage risk factors, and the need to separate these risk factors into discrete groups to evaluate with distal adverse outcomes. Second, I found that the vascular phenotype had the greatest rate of decline, and that certain combinations are riskier for cognitive decline and incident dementia than others. These results indicate that participants in the multisystem morbidity and vascular phenotypes are most likely further along in the cognitive process than other phenotypes. I also found minimal evidence of mediation by clinical CVD and depression suggesting that this relationship is independent from these intermediate variables. From a clinical perspective, the identification of phenotypes of cardiovascular damage may provide more specific and tailored interventions, or may better predict adverse events. These phenotypes need to be validated in other datasets, as well as modified to include markers that are easily implemented in clinical settings.
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