<p> Hypertension and reduced arterial distensibility are independent risk factors for cardiovascular disease. Previous research has found that isometric training reduces resting blood pressure (RBP) (Wiley et al. 1992; Taylor et al. 2003) yet the mechanisms responsible remain elusive. Improved arterial distensibility may contribute to this reduction in RBP. The purpose of the present study was threefold: 1) to replicate the RBP lowering effect of isometric handgrip (IHG) exercise; 2) to compare IHG and isometric leg press (ILP) based in their RBP lowering effects; and 3) to determine if central or peripheral arterial distensibility improved with IHG or ILP. The population examined was people whom were medicated for hypertension.</p> <p> RBP, as assessed by brachial oscillometry, and arterial distensibility, as assessed by Doppler ultrasound and applanation tonometry in the carotid, brachial and femoral arteries, were measured pre training, after 4 weeks of training, and post training. Participants performed unilateral IHG exercise (n=10) or ILP exercise (n=9) 3 times/week for 8 weeks at 30% MVC or acted as a non-exercising control group (n=5).</p> <p> Results indicated that the present study was unable to reproduce the RBP reductions noted in previous studies using IHG exercise. Also, the ILP exercise group did not experience reductions in RBP. Finally, neither central nor peripheral arterial distensibility improved in the IHG or ILP group when compared to the control group.</p> <p> Although these findings are contrary to our hypotheses one must consider that the control group examined contained very few subjects. This may have limited our ability to detect statistically significant changes in RBP and arterial distensibility.</p> / Thesis / Master of Science (MSc)

Cerebral palsy (CP) is no longer just a childhood disability. Children with CP grow up and become adolescents and eventually adults. However their risk of cardiovascular disease (CVD) and multimorbidity, defined as the presence of at least two chronic conditions, is poorly understood. This thesis sought to investigate CVD risk in individuals with CP and identify important health variables to understand and prevent multimorbidity development in this population. First, we discovered that adults with CP have an increased prevalence of CVD and an increased risk of death due to CVD compared to the general population, which raises concerns about CVD in people with CP and warrants further study. We investigated differences in cardiovascular health and moderate-to-vigorous physical activity (MVPA) in ambulatory adolescents and adults with CP between Gross Motor Function Classification System (GMFCS) levels I and II. Our findings suggest individuals who are GMFCS level II may be at increased risk for CVD in comparison to individuals who are GMFCS level I. We then evaluated longitudinal changes in risk factors of CVD in a cohort of individuals with CP. After a time interval of 4.0 ± 1.2 years, we found decreased absolute and relative brachial artery flow mediated dilation as measures of endothelial function, while carotid artery intima media thickness increased. We also discovered that 75% of participants with CP reported poor sleep quality, 80% engaged in less than the recommended 150 minutes of MVPA per week and 14% had poor eating behaviours. Taken together, this research suggests that individuals with CP experience accelerated aging for disease progression, specifically CVD, and that physical activity, sleep, and nutrition, together, could provide a framework for a lifestyle intervention to reduce and prevent multimorbidity risk in individuals with CP. / Thesis / Doctor of Philosophy (PhD) / Cerebral palsy is the most common child-onset physical disability. The disability can result in low levels of physical activity, obesity, and risk for morbid conditions that get worse over the lifecourse. The studies in this thesis furthered our understanding of cardiovascular disease and cardiovascular disease risk, investigated the relationship between physical activity and cardiovascular health, and evaluated changes in cardiovascular disease risk over time in individuals with cerebral palsy. We investigated three modifiable behaviours in individuals with cerebral palsy, which told us that they have poor sleep quality, do not engage in the recommended amount of physical activity, and could be at risk for poor nutrition. This work suggests that individuals with CP may be at an accelerated risk for cardiovascular disease, and that physical activity, sleep, and nutrition are important and modifiable factors that should be assessed and managed in this population.

The heart, as a vital organ, must pump continuously to deliver oxygenated blood to the tissues of the body. The physical stress of pumping is supported by the extracellular matrix (ECM), a dynamic protein scaffold inside and around the heart. While a regulated ECM is required to maintain heart function, aberrant or excessive ECM remodelling, called fibrosis, is associated with disease states and is a hallmark of cardiovascular disease. One major trigger of cardiovascular disease is obesity, and fibrotic remodelling is known to occur in this context. In order to study the impact of increased body size on heart function and the molecular and biophysical characteristics of the ECM, a larval overgrowth model for obesity in the genetic model Drosophila melanogaster has been developed and characterised. This model produces giant larvae twice as heavy as their wildtype counterparts, and allows a unique opportunity to study changes in the cardiac ECM in a simple genetic model. Results demonstrate a remarkable ability of the ECM to accommodate this increase in size. The muscles of the heart are particularly robust, and there are no obvious observable defects to the matrix. Preliminary results suggest Collagen fibres are thicker and more disperse. When observing heart functionality, the cross-sectional area of the heart lumen is increased significantly in giant larvae, both at diastole and systole. However, giant larvae display defects in contraction of the heart tube, characterised by an inability to contract fully at systole. This results in a less than proportional increase in stroke volume, and an increase in heart rate. Heart function of giant larvae is clearly affected by the increase in body size. To quantify the impact to the biophysical structure of the ECM, an atomic force microscopy protocol is being developed. / Thesis / Master of Science (MSc) / A known side effect of cardiovascular disease is fibrosis of the heart, a form of pathological extracellular matrix (ECM) remodelling. Fibrosis causes the stiffening of heart muscle, leading to impaired cardiac function. One of the main risk factors for the development of cardiovascular disease is obesity, and fibrosis is known to occur in this context. I have characterised changes in the morphology and physiology of the heart in a Drosophila model for obesity. The resulting cardiac hypertrophy reveals significant plasticity in the heart ECM, while heart contraction and output is compromised.

The global prevalence of chronic kidney disease (CKD) has risen at an accelerating rate, increasing the global healthcare burden for long-term and chronic care costs. Multiple risk factors including hypertension, diabetes, and dyslipidemia synergistically induce the progression of CKD. Chief among these factors are dyslipidemia and obesity; increased free fatty acid uptake due to excess consumption of lipid-rich diets has been shown to promote intra-renal lipid accumulation in several in vivo models and in patients in various stages of CKD. Furthermore, patients with renal disease are also at a substantially higher risk for atherosclerotic cardiovascular disease (CVD). In the general population, as well as in patients with renal disease, circulating low-density lipoprotein cholesterol (LDLc) is a well-established driver of atherosclerotic lesion development and CVD progression. In 2003, the proprotein convertase subtilisin/kexin type-9 (PCSK9) was identified as the third locus of familial hypercholesterolemia and was further characterized for its ability to enhance the degradation of the low-density lipoprotein receptor (LDLR). Since this seminal discovery, the development of monoclonal antibodies targeted against PCSK9 demonstrated a significant reduction in LDLc and subsequent CVD risk, establishing the remarkable ‘bench to bedside’ transition. However, the inherent role of PCSK9 in regulating lipid homeostasis remained unknown in different pathological conditions. In the first chapter of my thesis, I demonstrate that PCSK9 regulates the LDLR as a feedback mechanism to protect against non-alcoholic steatohepatitis (NASH) progression induced by a high-fat diet (HFD) challenge. Since its seminal discovery, PCSK9 was also characterized to modulate a wide variety of receptors known to play a crucial role in lipid metabolism including the cluster of differentiation 36 (CD36), the very low-density lipoprotein receptor (VLDLR), and the apolipoprotein E receptor 2 (ApoER2). Previously, we have demonstrated that the absence of PCSK9 promotes diet-induced non-alcoholic steatohepatitis and liver injury through increased surface expression of CD36. Given that these same receptors are well-expressed on renal epithelia, the second chapter of my thesis demonstrates that PCSK9 is also able to modulate renal lipid metabolism by attenuating tubular lipid accumulation and subsequent renal injury. Furthermore, when PCSK9 was first characterized by Seidah and colleagues in 2003, in situ hybridization of murine PCSK9 demonstrated that it was primarily expressed in the liver, but also well-expressed in the kidney cortex, cerebellum, and small intestines. Despite its expression in a wide range of tissues, the secretion of PCSK9 was exclusive to the liver, thus, questioning what the intracellular role of PCSK9 may be. Hence, my last chapter of my masters studies lies in establishing the role of intracellular PCSK9 expression in a cellular process known as endoplasmic reticulum (ER) stress in the kidney. ER stress is a phenomena which primarily occurs due to increased accumulation of misfolded polypeptides, and has been implicated in numerous metabolic diseases including hepatic steatosis, CKD, and neurodegenerative pathologies. Previously, we have demonstrated that overexpressing wild-type and variants of PCSK9 in a Pcsk9-/- mouse does not induce the activation of the unfolded protein response (UPR) and attenuates hepatic ER stress. Using a well-established CKD model, I show that Pcsk9-/- mice exhibit increased renal ER stress and injury relative to wild-type controls. Overall, my findings demonstrate for the first time that both extracellular and intracellular PCSK9 has the ability to modulate renal injury using two distinct mechanism to protect against CKD progression. / Thesis / Master of Health Sciences (MSc)

Sirtuin-1 (SirT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase expressed ubiquitously in the body. In the vasculature, SirT1 is present in endothelial and vascular smooth muscle cells (VSMCs), where it has been shown to promote anti-inflammatory and anti-oxidant effects. As a result, SirT1 is known to play a protective role in the vasculature wall from pathologies such as atherosclerosis, arterial stiffness, and aortic aneurysm. Hence, SirT1 is considered an attractive therapeutic target for vascular diseases and potentially, aging-related and metabolic diseases. However, currently available SirT1 activators have failed to reach the clinic. Thus, novel approaches to activate SirT1 are needed. In this study, we first sought to optimize a novel fluorescence-based SirT1 activity assay, with which to reliably assess intracellular SirT1 activity and the efficacy of SirT1 activators and inhibitors. We next sought to use the SirT1 activity assay to screen novel compounds identified by an in silico docking analysis and hypothesized to activate SirT1. Lastly, we generated adeno-associated viruses (AAV) overexpressing wildtype (WT) or a redox-resistant (3M) SirT1 to analyze the effects of overexpressing SirT1 in VSMCs, in normal and oxidative stress conditions. For the activity assay, our results showed that an optimal standard curve range was between 0 ng and 12 ng of substrate (acetylated-p53 peptide). After testing different commercially available human recombinant SirT1s, the Anaspec SirT1 of the highest concentration showed a decrease in measured fluorescence for acetylated-p53 peptide with higher SirT1 (ng), indicating the enzyme and the assay were functional. However, when novel small molecules (A4, B4, and G3) hypothesized to activate SirT1 were added to reactions, the total p53 peptide fluorescence values increased compared to the control, suggesting some interference of the molecules with the assay detection. After AAV infection in VSMCs, SirT1 expression, measured by HA-tag, increased for AAV WT (n=3, p=0.04) and similarly for AAV 3M SirT1, indicating that the AAVs efficiently infect VSMCs. SirT1 activity, measured by Western Blot as decreased acetylated-histone (H3), also appeared to increase for both AAV WT and AAV 3M. A similar trend was shown for VSMCs under oxidant stress conditions (n=2). In conclusion, we successfully established a standard curve range for a novel SirT1 activity assay. Further trials are needed to ensure activity assay reproducibility before testing the efficacy of SirT1 activators and inhibitors. Infection of AAV WT and 3M SirT1 led to an increase in the expression and activity of SirT1 in VSMCs. The expression of SirT1 by AAV may be a promising therapeutic option for in vivo prevention and treatment of vascular diseases. / 2026-03-01T00:00:00Z

Type II Diabetes Mellitus (T2D) and cardiovascular diseases (CVD) are non-communicable chronic diseases that involves impairments in glucose metabolism and vascular function. Multiple factors may increase the risk for T2D, including but not limited to genetics, obesity and lifestyle, such as physical inactivity and diet. The gut microbiota, the human's largest population of microorganisms, plays an essential role in health and disease. The physiology and function of the gastrointestinal tract can be influenced by the diet. Phosphatidylcholine (PC), a source of choline in the diet, is rich in Western-type diets. Gut microbiota metabolize choline to trimethylamine (TMA) which circulates and is oxidized in the liver to form trimethylamine N-oxide (TMAO). As a result, ingestion of PC or choline could increase levels of TMAO. Preclinical studies indicate a role of TMAO in the development of atherosclerosis. Likewise, multiple observations support a potential role of TMAO in the development of insulin resistance and T2D. Much of the research has been conducted on rodent models, while others are observational human studies. Whether acute and short-term increases in TMAO contribute to impairments in insulin sensitivity in humans remains unknown. To address this, we performed two studies utilizing a double-blind, placebo controlled, crossover design. Eligible participants consumed a 1000mg/day dose of choline bitartrate and placebo (maltodextrin) the night before each testing session (for the acute choline study) or for 4 weeks (for the short-term choline ingestion study). Oral glucose tolerance test, continuous glucose monitoring, flow-mediated dilation, and applanation tonometry was performed the day after the acute choline load and before and after the short-term choline ingestion period. We hypothesized that gut microbiota-generated increase in TMAO will impair insulin sensitivity, glucose tolerance, endothelial function and arterial stiffness in healthy sedentary humans. Following acute choline ingestion, significant increases in plasma TMAO (p = 0.013) and choline (p = 0.003) were evident. There was no statistically significant difference in insulin sensitivity, glucose tolerance or in any of the endothelial function and arterial stiffness measurements. Four weeks of 1000mg choline ingestion per day, significantly increased plasma (p = 0.042) and urine (p = 0.008) TMAO concentrations compared to the placebo. However, no significant differences were observed for any other measurements of insulin sensitivity, glucose tolerance, glycemic variability, endothelial function, and arterial stiffness. More research is needed to elucidate the mechanisms behind the mechanistic observations between elevated TMAO concentrations and T2D and CVD. / Doctor of Philosophy / Type 2 diabetes mellitus (T2D) and cardiovascular diseases (CVD) increase the risk of all-cause mortality. Choline is a nutrient that can be found in foods such as red meat, dairy, fish, and eggs. Choline is metabolized from bacteria in our gut and a metabolite called trimethylamine (TMA) is formed. TMA is then oxidized in the liver and trimethylamine-N-oxide (TMAO) is produced. A Western-type diet is rich in red meat, dairy, fish, and eggs and has been shown to increase production of the compound TMAO. Preclinical studies have suggested a causal role of TMAO in atherosclerosis and T2D and elevated plasma TMAO concentrations have been associated with an increased risk for CVD and T2D in observational studies. However, the causal nature of this relationship in humans is unknown. The studies described herein aimed to investigate the effects of increases in TMAO on insulin sensitivity and vascular function in healthy adults. The first study tested the effect of increasing TMAO on insulin sensitivity, glucose tolerance, and vascular function following an acute choline load (1000mg) and placebo (carbohydrate) the night before each testing session. In the second study, we examined the effect of increasing TMAO on insulin sensitivity, glucose tolerance, and vascular function in healthy adults, following a short-term choline load (1000mg/day) and placebo (carbohydrate) for 4 weeks. Acute and short-term choline ingestion significantly increased plasma TMAO concentrations. No significant differences were observed following acute or short-term choline ingestion for any measurement of insulin sensitivity, glucose tolerance 24-hout glycemic variability, vascular function., and arterial stiffness.

One hundred twenty-six right-handed undergraduate men and women underwent physiological measurements of SBP, DBP, and HR before and after verbal and figural fluency tasks, used as stressors. Dynamic and functional cerebral regulation of cardiovascular reactivity was assessed, specifically, the role that the frontal lobes have in regulating SBP, DBP, and HR in men and women. Sex differences in the functional cerebral regulation of these cardiovascular factors were predicted. Hostility was assessed in these participants, using the Cook-Medley Hostility Inventory (6 total groups of 21 participants each: high-, mid-, and low-hostile participants were identified). Sex and group (hostility) differences were predicted, as well as task (fluency type) differences. Comparisons were also made from a time estimation task (30 and 180 seconds), and the effect that women's menstrual cycle had on fluency. The MCSDS and the STAI were administered. The principal findings of the current investigation were that the verbal fluency task raised SBP across sex and group, that both stressors raised SBP or DBP in different patterns (no sex differences were found), while stressors interacted with both sex and group. High-hostile men performed better on the first trial of the verbal fluency test compared to low-hostile men, while high-hostile women performed worse on the first trial of the verbal fluency test, compared to low-hostile women. Men perseverated more on each trial of the verbal fluency test, while women perseverated less across trials. High-hostile men's time perception seems to be more rapid than low-hostile men, while for women it is the opposite. Women reported significantly more stress from the figural fluency task than men. Women in the luteal phase of menstruation did better on the verbal fluency test than women in the follicular phase of menstruation, and hostility and menstrual phase interact with verbal fluency. This study encourages the consideration of neuropsychological sex differences in order to better understand cardiovascular regulation mechanisms and disease, leading to the development of improved prevention and behavioral management programs. Findings supporting this idea may bring about a new research focus, as some forms of cardiovascular disease may be more appropriately investigated as arising from neuropsychological problems. / Ph. D.

This experiment was primarily designed to identify higher cortical correlates of cardiovascular arousal. Low- and high-hostile, right-handed, undergraduate men were identified using the Cook Medley Hostility Scale (CMHS). All participants (N = 30) completed the cold pressor paradigm. Cardiovascular (heart rate, systolic blood pressure, and diastolic blood pressure) and electroencephalographic (beta magnitude) data were collected before and after the stressor. As predicted, high-hostiles showed greater increases of heart rate and systolic blood pressure to the stressor relative to low-hostiles. The primary findings of this research include significantly greater beta magnitude recorded by the T3, relative to F7, electrode among low-hostiles. This may suggest that low-hostiles experience left-frontal disinhibition of left-temporal regions, thereby strengthening cardiovascular regulation during the cold-pressor stress. In addition, irrespective of condition, high-hostiles evidenced significantly greater beta magnitude at regions corresponding to the F7 and F8 electrodes. This perhaps suggests that high-hostiles have a relative inability to increase their rostral modulation of posterior systems related to cardiovascular activity/regulation. Low- and high-hostiles did not, however, evidence reliable differences in their ability to monitor cardiovascular arousal to the cold-pressor stress. Findings are discussed in terms of a systems approach, and pertinent future research is recommended. This research did not support the prominent neuropsychological theories of cardiovascular regulation proposed by Heilman et al. (1993) and Tucker and Williamson (1984). Rather, the results may suggest that right- and left-cerebral mechanisms may be primarily responsible for sympathetic and parasympathetic cardiovascular arousal, respectively. / Ph. D.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Age is a primary risk factor for the development of CVD and middle-age is a vulnerable period where risk factors for the disease begin to exceed diagnostic thresholds. Interest has increased for the use of low carbohydrate high fat (LCHF) ketogenic diets due to their reported improvements for cardiometabolic health. Supplementation with exogenous ketone esters (KE) has been shown to increase plasma β-hydroxybutyrate (BHB) and mimic the metabolic effects of LCHF ketogenic diets. Evidence suggests elevated concentrations of plasma BHB may lower blood pressure, improve vascular function, attenuate hyperglycemic responses, and enhance cognitive function. The majority of research has been conducted in preclinical models, and whether exogenous KE supplementation has similar improvements in humans of any ages remains relatively unanswered. To address this we conducted a randomized, placebo controlled, crossover design study in healthy, sedentary, middle to older aged adults who received the exogenous KE (or placebo), and consumed the supplement for 2-weeks (3x/day, 15 minutes prior to each meal; breakfast, lunch, and dinner). Our first hypothesis was to test that KE supplementation would improve vascular function by increasing flow-mediated dilation, reducing arterial stiffness, and lowering blood pressure. Secondly, we hypothesized that KE supplementation would attenuate the glycemic response to an oral glucose tolerance test, improve glycemic variability, and show reductions in postprandial glucose levels. Thirdly, we tested the hypothesis that KE supplementation would improve cognitive performance by showing improvements in processing speed, memory, attention control, and executive functions. In support of our first hypotheses, KE supplementation increased flow-mediated dilation (8.1 ± 1.3 vs. 7.7 ± 1.2%, p = 0.023), but it did not show any difference in arterial stiffness or blood pressure. In contrast to our second hypotheses, following the KE supplementation intervention there were no significant difference from the placebo in terms of glycemic response, variability or mean 2-hour post-meal glucose. In support of our third hypotheses, we found a significant improvement in measures of working memory (7.55 ± 0.93 vs. 7.27 ± 0.29, p = 0.026) and inhibitory control (80 ± 38 vs. 87 ± 32ms, p = 0.035) following the 14-day KE supplementation. More research is needed to elucidate the effects of KE on cardiometabolic health and cognition. / Doctor of Philosophy / Recently there has been an increase in the popularity of low carbohydrate high fat (LCHF) ketogenic diets, with advocates for the diet claiming increased benefits in weight loss and blood glucose control, therefore leading to an increased interest for its use in the treatment for cardiovascular disease, obesity, and diabetes. As more evidence has accumulated much of the impact LCHF ketogenic diets are said to have, has been attributed to a state known as nutritional ketosis, which occurs in response to the restriction of carbohydrates from the diet. Ketone esters (KE) have been shown to effectively elevate ketone bodies (alternative energy produced by the body during times when glucose stores are low) without the need of altering one's own diet, however, this method of inducing ketosis is still lacking evidence for its impact on cardiometabolic health in humans. The purpose of these studies is to determine the effect of having sustained elevations of ketone bodies on our health and cognition in humans. Study 1 included healthy, sedentary middle to older aged adults who consumed a KE for 2-weeks (3x/day, prior to each meal) and a placebo. Following supplementation participants completed test to assess our vascular health and blood sugar control. Study 2 included healthy, sedentary middle to older aged adults who consumed a KE for the same 2-weeks (3x/day, prior to each meal) and a placebo. Participants underwent a series of tests to assess cognitive performance. Overall, after a 2-week supplementation period we found significant improvements in our blood vessel function and with cognitive performance where we saw improvements in working memory, and inhibitory control.

The American Heart Association Life's Simple 7 (LS7), a metric that classifies cardiovascular health using modifiable risk factors, has been reported to be associated with cognitive function. However, the assessment of cognitive function in prior studies has been limited to relatively crude global measures. We hypothesized that greater LS7 scores at baseline are associated with less cognitive decline and lower incidence of dementia and Alzheimer's. Using data from the core Health and Retirement Study survey (2012-2018), 2013 Health Care and Nutrition Questionnaire and enhanced face-to-face interviews we will evaluate cognitive scores in relation to LS7. The participants included in this analysis (n = 2,753) are greater than 50 years of age without dementia. A global cognitive score was calculated using the combination scores on multiple cognitive tests that include measurements of semantic memory, quantitative reasoning, episodic memory, and executive functioning. Changes in cognitive scores are evaluated based on marginal effects after adjustments for confounding variables. Baseline LS7 scores (0-14) were calculated using information on smoking habits, body mass index, habitual diet, blood pressure, non, physical activity, and hemoglobin a1c. Results were analyzed using linear mixed models fit with random intercepts and the use of Huber-White variance estimates to analyze the results. Knots were introduced to explain non-linear change in respondents. Global cognitive scores in all respondents decreased more between baseline to year two and year two to year four than year four to year six (ΔB-2: -2.796, Δ2-4: -3.362 v. Δ4-6: -1.191). A one unit increase in LS7 score presented a protective effect and slowed the rate of decline by 0.11 unit in global cognitive scores between baseline and year two. The protective effect was lower between year two and four (0.07 units) and non-significant between year four and six. Black respondents did not respond similarly in models than white respondents. A one unit increase in LS7 score increased the rate of decline from baseline to year two and year two to year 4 in black respondents (p<0.001, p<0.05). LS7 scores had no significant interaction with global cognitive scores between year 2 and 6. Serial 7 scores did not significantly change over time in any of the racial categories. A unit increase in LS7 scores showed a marginal protective effect on memory scores from year two to four in all respondents (r=0.03, p<0.001). In white respondents, higher LS7 scores had a protective effect on memory scores (r=0.01, p<0.05). The probability of developing dementia or Alzheimer's over the study period was the highest for males (P = 3.6%) than females (P = 3.3%) and lowest for white, females (P=13%) and highest for black, males (P=15%). Having higher LS7 scores at baseline is associated lower cognitive decline over a 6-year period in white, older adults. LS7 scores at baseline delayed word recall/memory scores over time but not serial 7/executive functioning scores. LS7 scores at baseline are not associated with lower incidence of cognitive impairment and dementia. Findings suggest better habits formed earlier in life have a better protective effect than late-life habits / Master of Science / The United States is dealing with a rapidly aging population. By the year 2035, there is expected to be more adults over the age of 65 than children. As the number of older adults increases as will the number of new and existing cases of Alzheimer's and other dementias. The burden of older adults with Alzheimer's and dementia strains the U.S. healthcare system therefore new research is emerging on interventions used to slow the onset of this life-altering disease before critical and expensive care is required. One method that has been effective is modifying lifestyle behaviors. In 2010 the American Heart Association classified the Life's Simple 7 (LS7) metrics which involved both behavioral and biological measures for cardiovascular risk assessment in Americans. The LS7 metrics include smoking behaviors, physical activity, diet, body mass index, blood pressure, cholesterol, and fasting blood glucose. The American Heart Association's LS7 metric adherence during early and mid-life has been shown to decrease risk for Alzheimer's and dementia, however, research of adherence in late-life is limited. Preventing late-life onset of dementia is vital to older adults therefore this study aims to observe late-life adherence LS7 and change in cognitive functioning over a 6-year period (2012-2018). Participants included in this study are from the Health and Retirement Study (HRS) that are 50 years and older without diagnoses of dementia or Alzheimer's at the time of baseline measurement in 2012. Late-life adherence to Life's Simple 7 metrics are associated with slower rates of cognitive decline in white respondents. The Life's Simple 7 metric is not significantly associated lower cases of dementia and is associated slower rates of decline in memory but not executive functioning. This study aimed to expand evidence for racial differences on global cognitive changes and domain-specific cognitive measurements and the effect Life's Simple Seven scores have on that relationship.