Obesity is an accumulation of adipose tissue to the point of negative health outcomes; the association of obesity with type 2 diabetes and cardiovascular disease is particularly profound. Notably, obesity has begun to be associated with impairments in cognitive function; however, the underlying cellular mechanisms are poorly understood. Behavioural studies have demonstrated a link between a high fat diet and impaired hippocampal function, and our aim was to characterize protein level changes in the hippocampus of an obese female rat model. Female rats were fed either a control diet (CD; 10% kcal from fat), or a high-fat diet (HFD; 45% kcal from fat) for 16 weeks. Body weight, food consumption, fasting blood glucose levels, and glucose tolerance were monitored. Upon sacrifice brain, liver, adrenal glands, spleens and fat pads were harvested and analyzed. Plasma leptin and insulin levels were also measured. The distribution of NMDA receptor subunits was examined by using either cell-surface biotinylation, or differential filtration-centrifugation followed by immunoblotting. The feeding protocol induced an obese phenotype in female rats characterized by larger fat pads, spleens and adrenal glands, as well as greater problems handling a glucose load. However, cellular, surface and synaptic expression of NMDA receptor subunits (GluN1, GluN2A & GluN2B) were not significantly altered, which suggests that changes downstream of the receptor may be responsible for the effects of HFD on cognitive behaviour.

Background: Inflammation, if uncontrolled, can promote the formation of colon cancer. Intestinal lymphocytes (IL) are immune cells that can participate in inflammation through the generation of cytokines and by causing direct cellular injury. Apoptosis, or programmed cell death, regulates the population of lymphocytes and dysregulation of this process results in the prolonged activation of IL that occurs during inflammation. Therefore, inducing apoptosis of IL is a viable mechanism by which inflammation and possibly colon carcinogenesis could be prevented. Experimentally, inflammation may be induced in mice by: 1) the addition of the chemical irritant dextran sulfate sodium (DSS) to drinking water or 2) exposure to acute exercise (AE; intense treadmill running). Bovine lactoferrin (bLf) is a dietary whey protein with demonstrated ability to promote anti-inflammatory responses by reducing pro-inflammatory or increasing anti-inflammatory cytokine concentrations within the intestine. There are also reports that bLf can alter apoptotic proteins in the intestinal epithelium to favour cell death. Moreover, athletes have been reported to supplement their diets with whey protein; it is also known clinically that after heavy competition some athletes may experience gastrointestinal distress. The role, however, of bLf in reducing inflammation by initiation of apoptosis or alteration of cytokine levels in IL has not been examined. Objectives: The primary objective of this research was to determine whether dietary bLf affects mouse IL apoptosis and cytokine concentrations in: 1) a normal, non-inflamed state, 2) following AE challenge and 3) following DSS treatment. A second objective was to directly examine the potential protective effects of dietary bLf from inflammatory damage caused by DSS and AE challenge when administered alone or in combination with a carcinogen. Methods: A total of 252 female C57BL/6 mice were used in the experiments. Apoptotic proteins (Bcl-2, caspase 3, Bax, cytochrome c), inflammatory cytokine proteins (TNF-α and IL-10) and a transcription factor for pro-inflammatory cytokines (NFκB) were determined in isolated mouse IL by Western blot analysis. Flow cytometry was used to determine the extent of apoptosis in mouse IL subsets by measuring phosphatidylserine surface expression using Annexin V+ (ANN+) and propidium iodide staining. Tissue inflammation was determined by histology (H&E staining) on segments of mouse small and large intestine. Diets were prepared and pelletted to contain 20% total protein and contained either bLf or were the control formulation (no bLf). Mice were exposed to bLf containing diets for 4 d or 12 d prior to sacrifice. DSS was provided at 5% in the drinking water for 4 consecutive days prior to sacrifice. Animals were subjected to three repeated bouts of AE (each separated by 24 h rest) involving treadmill running and sacrificed either immediately or 24 h after the final exercise bout. In the experiment involving carcinogenesis, mice were given two subcutaneous injections of azoxymethane (AOM), followed by a two week incubation period, and subsequently exposed to bLf or the control diet. Results: Results from the first experiment determined that 2.0% bLf was effective at reducing mouse IL levels of TNF-α (p<0.05) (pro-inflammatory) and increasing the percentage of apoptotic CD4+ IL (CD4+/ANN+, p<0.05) in healthy mice. Thus, 2.0% bLf was used for the subsequent experiments. Dietary bLf administration in mice exposed to AE was associated with lower levels in mouse IL of the anti-apoptotic protein Bcl-2 (p<0.01) and of TNF-α (p<0.05) and NFκB (p<0.05), both pro-inflammatory proteins. Further, the exercise protocol resulted in oxidative stress, as measured by 8-iso prostaglandin F2α levels in plasma, but did not induce intestinal inflammation, evident by the absence of both tissue damage and infiltration of immune cells. Following DSS treatment, mice supplemented with bLf enriched diets had lower levels of both TNF-α (non-significant, 34% reduction) and NFκB (p<0.05) and increased concentrations (p<0.01) of cytochrome c, a mitochondrial protein associated with cell death. DSS exposure in mice resulted in gross morphological alterations and infiltration of immune cells in the small and large intestine; these changes in tissue histology were not affected by the addition of bLf. Mice injected with AOM and then subjected to DSS, but not AE, had increased numbers (p<0.001) of aberrant crypts, preneoplastic colonic lesions, compared to animals only receiving AOM injection. Dietary bLf did not affect any of these carcinogenic processes. Conclusions: Collectively, these results suggest that dietary bLf administration reduces pro-inflammatory cytokine levels and has limited effects on apoptosis of mouse IL. Moreover, these modifying effects of bLf did not result in mucosal protection, as evident in the inability of this protein to reduce DSS-induced tissue damage or formation of aberrant crypts. Physiological and Clinical Implications: Although the long term physiological consequences of bLf supplementation in the regulation of intestinal immune homeostasis require further study, the following clinical implications are tentatively suggested by the findings from this thesis research. First, dietary bLf supplementation does not provide direct protection of the intestine during inflammation either with or without exposure to the carcinogen (i.e., AOM); hence, bLf (at least in the dietary concentration and exposure used in these experiments) may not be useful in reducing the formation of aberrant crypts and carcinogenesis. Second, dietary bLf should not be recommended as a supplement at this time for athletes experiencing intestinal distress since it had no impact on tissue indicators of disease in a model (DSS) shown to produce extensive inflammation and tissue pathology. Nonetheless, the findings raise the possibility that bLf can modify both cytokines and apoptotic protein expression in IL and may influence some aspects of inflammatory processes in the gut.

Objective: Significant efforts have been made to address childhood obesity. Overtime we have realized obesity requires strong political leadership and population level interventions, considering there are many environmental factors contributing to obesity. Stakeholders in Manitoba have created a policy that in combination with other initiatives is attempting to increase physical activity and in turn combat the obesity epidemic. Therefore the objective of this study was to understand the complexities involved with developing an innovative policy. Results from this study would refine our understanding on how policy is enacted, provide information on the support for and resistance of policies for decision makers in the future, and contribute an historical record to Manitoba stakeholders. Mobilizing these context-specific findings will inform other Canadian provinces or jurisdictions on how to develop, integrate and implement a similar policy. Methods: This study employed a retrospective single case study design. Twelve participants were purposively selected from provincial and local-levels and invited to participate in a 45 minute semi-structured telephone interview examining the developmental processes involved in the Physical Education/Health Education policy. The data consisted of two sources. The primary sources consisted of 9 interview transcripts and the secondary sources consisted of several important documents that assisted filling in gaps pertaining to the policy. Qualitative analyses were separated into two parts. The first part identified common themes from the interview transcripts, and the second part organized the data into stages from an existing model for analysis. Results: The analysis identified several influential factors that facilitated moving the policy process forward. More specifically, the factors existing between the Policy Formulation and Implementation stages were critically analyzed revealing collaboration and on-going communication as important features for developing and implementing policies. The Stages Model proved to be relatively uninformative yielding minimal information to understanding the policy process. Therefore researchers should seek out additional theories or models in future research. Conclusions: The findings from this research project have contributed valuable knowledge and insights. Lessons learned from this project will assist future decision makers on how to develop and implement a similar policy in another province or jurisdiction.

Ensuring students are well fed can have positive social, behavioural, and academic benefits. Schools reach almost all children and the food they consume there can significantly contribute to their overall dietary intake. Universal access to school nutrition programs (SNPs) can ensure that children at-risk for poor nutrient intake have access to safe, healthy foods, thereby promoting growth and development and enhancing academic performance. The purpose of this research study was to evaluate the processes and structures of an Ontario Region’s student nutrition programs and to determine how the public health departments’ staff can support the program. This mixed method evaluation included a quantitative survey (n=62; 76% response rate) and qualitative interviews involving 22 program coordinators. The survey elicited a description of programs and variations in components being offered. Interviews with coordinators provided information regarding strengths, weaknesses, opportunities, and threats. Current and potential partnerships between programs and health units were also evaluated. All school levels were well represented in both quantitative and qualitative methods, with community-based programs being under-represented. Survey results showed that teachers and volunteer program coordinators were the most involved in planning and delivering programs. Also, more programs had public health inspectors involved (22.4%), compared to public health nurses (14.0%) or nutritionist/dietitians (9.1%). Although only 17.3% of coordinators reported wanting more general public health involvement, 27.8% wanted menu planning and nutrition support, and 25.5% wanted food safety training. Overall, qualitative results showed that SNPs in the Region varied enormously. The major strengths reported by coordinators included universality, the ability to reach needy students, and the ability to provide social opportunities for students. Major weaknesses included forming partnerships, lack of volunteers, scheduling/timing issues, and coordinator work-load. Common threats included lack of sustainable funding, complexity in tracking program use, unreliable help, and school administration conflicts. Finally, opportunities described by coordinators included assistance with menu planning, expansion of program offerings, and assistance with finding community partners. This research has identified strategies to help support SNPs. Because not one program in the Region is run the same way, multiple strategies need to be in place to support programs at individual levels. Therefore, health units can have a major role, whether it is through menu planning, food safety training, helping coordinators find healthy food options, or helping them build partnerships to enhance program support and operations.

Background: Inflammation, if uncontrolled, can promote the formation of colon cancer. Intestinal lymphocytes (IL) are immune cells that can participate in inflammation through the generation of cytokines and by causing direct cellular injury. Apoptosis, or programmed cell death, regulates the population of lymphocytes and dysregulation of this process results in the prolonged activation of IL that occurs during inflammation. Therefore, inducing apoptosis of IL is a viable mechanism by which inflammation and possibly colon carcinogenesis could be prevented. Experimentally, inflammation may be induced in mice by: 1) the addition of the chemical irritant dextran sulfate sodium (DSS) to drinking water or 2) exposure to acute exercise (AE; intense treadmill running). Bovine lactoferrin (bLf) is a dietary whey protein with demonstrated ability to promote anti-inflammatory responses by reducing pro-inflammatory or increasing anti-inflammatory cytokine concentrations within the intestine. There are also reports that bLf can alter apoptotic proteins in the intestinal epithelium to favour cell death. Moreover, athletes have been reported to supplement their diets with whey protein; it is also known clinically that after heavy competition some athletes may experience gastrointestinal distress. The role, however, of bLf in reducing inflammation by initiation of apoptosis or alteration of cytokine levels in IL has not been examined. Objectives: The primary objective of this research was to determine whether dietary bLf affects mouse IL apoptosis and cytokine concentrations in: 1) a normal, non-inflamed state, 2) following AE challenge and 3) following DSS treatment. A second objective was to directly examine the potential protective effects of dietary bLf from inflammatory damage caused by DSS and AE challenge when administered alone or in combination with a carcinogen. Methods: A total of 252 female C57BL/6 mice were used in the experiments. Apoptotic proteins (Bcl-2, caspase 3, Bax, cytochrome c), inflammatory cytokine proteins (TNF-α and IL-10) and a transcription factor for pro-inflammatory cytokines (NFκB) were determined in isolated mouse IL by Western blot analysis. Flow cytometry was used to determine the extent of apoptosis in mouse IL subsets by measuring phosphatidylserine surface expression using Annexin V+ (ANN+) and propidium iodide staining. Tissue inflammation was determined by histology (H&E staining) on segments of mouse small and large intestine. Diets were prepared and pelletted to contain 20% total protein and contained either bLf or were the control formulation (no bLf). Mice were exposed to bLf containing diets for 4 d or 12 d prior to sacrifice. DSS was provided at 5% in the drinking water for 4 consecutive days prior to sacrifice. Animals were subjected to three repeated bouts of AE (each separated by 24 h rest) involving treadmill running and sacrificed either immediately or 24 h after the final exercise bout. In the experiment involving carcinogenesis, mice were given two subcutaneous injections of azoxymethane (AOM), followed by a two week incubation period, and subsequently exposed to bLf or the control diet. Results: Results from the first experiment determined that 2.0% bLf was effective at reducing mouse IL levels of TNF-α (p<0.05) (pro-inflammatory) and increasing the percentage of apoptotic CD4+ IL (CD4+/ANN+, p<0.05) in healthy mice. Thus, 2.0% bLf was used for the subsequent experiments. Dietary bLf administration in mice exposed to AE was associated with lower levels in mouse IL of the anti-apoptotic protein Bcl-2 (p<0.01) and of TNF-α (p<0.05) and NFκB (p<0.05), both pro-inflammatory proteins. Further, the exercise protocol resulted in oxidative stress, as measured by 8-iso prostaglandin F2α levels in plasma, but did not induce intestinal inflammation, evident by the absence of both tissue damage and infiltration of immune cells. Following DSS treatment, mice supplemented with bLf enriched diets had lower levels of both TNF-α (non-significant, 34% reduction) and NFκB (p<0.05) and increased concentrations (p<0.01) of cytochrome c, a mitochondrial protein associated with cell death. DSS exposure in mice resulted in gross morphological alterations and infiltration of immune cells in the small and large intestine; these changes in tissue histology were not affected by the addition of bLf. Mice injected with AOM and then subjected to DSS, but not AE, had increased numbers (p<0.001) of aberrant crypts, preneoplastic colonic lesions, compared to animals only receiving AOM injection. Dietary bLf did not affect any of these carcinogenic processes. Conclusions: Collectively, these results suggest that dietary bLf administration reduces pro-inflammatory cytokine levels and has limited effects on apoptosis of mouse IL. Moreover, these modifying effects of bLf did not result in mucosal protection, as evident in the inability of this protein to reduce DSS-induced tissue damage or formation of aberrant crypts. Physiological and Clinical Implications: Although the long term physiological consequences of bLf supplementation in the regulation of intestinal immune homeostasis require further study, the following clinical implications are tentatively suggested by the findings from this thesis research. First, dietary bLf supplementation does not provide direct protection of the intestine during inflammation either with or without exposure to the carcinogen (i.e., AOM); hence, bLf (at least in the dietary concentration and exposure used in these experiments) may not be useful in reducing the formation of aberrant crypts and carcinogenesis. Second, dietary bLf should not be recommended as a supplement at this time for athletes experiencing intestinal distress since it had no impact on tissue indicators of disease in a model (DSS) shown to produce extensive inflammation and tissue pathology. Nonetheless, the findings raise the possibility that bLf can modify both cytokines and apoptotic protein expression in IL and may influence some aspects of inflammatory processes in the gut.

Objective: Significant efforts have been made to address childhood obesity. Overtime we have realized obesity requires strong political leadership and population level interventions, considering there are many environmental factors contributing to obesity. Stakeholders in Manitoba have created a policy that in combination with other initiatives is attempting to increase physical activity and in turn combat the obesity epidemic. Therefore the objective of this study was to understand the complexities involved with developing an innovative policy. Results from this study would refine our understanding on how policy is enacted, provide information on the support for and resistance of policies for decision makers in the future, and contribute an historical record to Manitoba stakeholders. Mobilizing these context-specific findings will inform other Canadian provinces or jurisdictions on how to develop, integrate and implement a similar policy. Methods: This study employed a retrospective single case study design. Twelve participants were purposively selected from provincial and local-levels and invited to participate in a 45 minute semi-structured telephone interview examining the developmental processes involved in the Physical Education/Health Education policy. The data consisted of two sources. The primary sources consisted of 9 interview transcripts and the secondary sources consisted of several important documents that assisted filling in gaps pertaining to the policy. Qualitative analyses were separated into two parts. The first part identified common themes from the interview transcripts, and the second part organized the data into stages from an existing model for analysis. Results: The analysis identified several influential factors that facilitated moving the policy process forward. More specifically, the factors existing between the Policy Formulation and Implementation stages were critically analyzed revealing collaboration and on-going communication as important features for developing and implementing policies. The Stages Model proved to be relatively uninformative yielding minimal information to understanding the policy process. Therefore researchers should seek out additional theories or models in future research. Conclusions: The findings from this research project have contributed valuable knowledge and insights. Lessons learned from this project will assist future decision makers on how to develop and implement a similar policy in another province or jurisdiction.

Ensuring students are well fed can have positive social, behavioural, and academic benefits. Schools reach almost all children and the food they consume there can significantly contribute to their overall dietary intake. Universal access to school nutrition programs (SNPs) can ensure that children at-risk for poor nutrient intake have access to safe, healthy foods, thereby promoting growth and development and enhancing academic performance. The purpose of this research study was to evaluate the processes and structures of an Ontario Region’s student nutrition programs and to determine how the public health departments’ staff can support the program. This mixed method evaluation included a quantitative survey (n=62; 76% response rate) and qualitative interviews involving 22 program coordinators. The survey elicited a description of programs and variations in components being offered. Interviews with coordinators provided information regarding strengths, weaknesses, opportunities, and threats. Current and potential partnerships between programs and health units were also evaluated. All school levels were well represented in both quantitative and qualitative methods, with community-based programs being under-represented. Survey results showed that teachers and volunteer program coordinators were the most involved in planning and delivering programs. Also, more programs had public health inspectors involved (22.4%), compared to public health nurses (14.0%) or nutritionist/dietitians (9.1%). Although only 17.3% of coordinators reported wanting more general public health involvement, 27.8% wanted menu planning and nutrition support, and 25.5% wanted food safety training. Overall, qualitative results showed that SNPs in the Region varied enormously. The major strengths reported by coordinators included universality, the ability to reach needy students, and the ability to provide social opportunities for students. Major weaknesses included forming partnerships, lack of volunteers, scheduling/timing issues, and coordinator work-load. Common threats included lack of sustainable funding, complexity in tracking program use, unreliable help, and school administration conflicts. Finally, opportunities described by coordinators included assistance with menu planning, expansion of program offerings, and assistance with finding community partners. This research has identified strategies to help support SNPs. Because not one program in the Region is run the same way, multiple strategies need to be in place to support programs at individual levels. Therefore, health units can have a major role, whether it is through menu planning, food safety training, helping coordinators find healthy food options, or helping them build partnerships to enhance program support and operations.

Objectives: To assess the intake of milk and alternatives, calcium, and vitamin D in on-reserve First Nations youth in Ontario, Canada; and the relationship of these nutrients to body mass index. To assess the impact of a simple food provision program on the intakes of milk and alternatives among First Nations youth in Kashechewan First Nation and Attawapiskat First Nation, Ontario, Canada. To assess the process of implementing a comprehensive school nutrition education program, as well as its effects on the intake of milk and alternatives, as well as knowledge, intentions, and self-efficacy among First Nations youth in Fort Albany First Nation, Ontario. Methods: Twenty-four hour diet recall data collected by web-based survey between November 2003 and June 2010 (including pre- and post-program) were used to assess intakes. Milk and alternatives, calcium, and vitamin D intakes were described and compared to food and nutrition standards and to intakes in the general population (CCHS cycle 2.2), and related to BMI. Data collected in different years for the same community and season were used to assess yearly effects on milk and alternatives intake (four communities). Data collected in the same year and season but from different communities were used to assess latitudinal effects on milk and alternatives intake (four community pairs). Paired change in intakes was evaluated one week-post snack program implementation in Kashechewan and Attawapiskat, as well as one year post-program in Kashechewan. Change in intakes as well as knowledge, self-efficacy, and intentions were evaluated in Fort Albany after the completion of a comprehensive school-based program. Student (grades 6-8), teacher (from grades K-8), and parent impressions were collected via questionnaires and focus groups. Results: Mean intakes of milk and alternatives, calcium, and vitamin D were below recommendations and levels seen in the general population. No relationship between body mass index and milk and alternatives, calcium, or vitamin D intake was detected. Latitudinal and yearly variation in intakes was detected in the communities under study. Pilot school food provision programs improved intakes in the short-term under close to ideal circumstances, including adequate dedicated personnel and resource support. After one week, calcium intake increased in Kashechewan (p=0.044), while milk and alternatives (p=0.034) and vitamin D (p=0.022) intakes increased in Attawapiskat. Multiple logistical barriers meant that these improvements were not sustained in the long-term. A comprehensive program in Fort Albany was successful in increasing knowledge (p=0.050) and intentions (p=0.010) towards milk and alternatives intake. Students were generally grateful for the snack programs, and especially enjoyed the hands-on lessons in Fort Albany. Teachers in Kashechewan thought that the snack program was very valuable for students and helped with their alertness and attentiveness. In Fort Albany, teachers noted that it was helpful to have an outside person who could devote all of their time to teaching the students about nutrition; they thought that the students gained a whole new perspective about nutrition via the program. Parents in Fort Albany were enthusiastic about the school nutrition program, but noted availability and cost as major barriers to healthy eating. Conclusions: The low milk and alternatives, calcium, and vitamin D intakes seen in the study population parallel results seen in studies of other Canadian Aboriginal populations. Further study is needed to clarify the relationship between milk & alternatives intake and BMI in this population. Latitudinal and yearly variations in intake were identified, and therefore should be accounted for when tailoring interventions to specific First Nations; the needs, opportunities, and barriers in each case may differ significantly. This study demonstrated that school food provision programs were valued by students, parents, and teachers; and were efficacious in improving short-term intakes. Comprehensive programs were shown to improve student knowledge and intentions to make healthy food choices. In order to support long-term effectiveness, the barriers identified through this research, including the need for adequate and sustainable resources, must be addressed.

Objective: The objective of this study was to understand school administrators’ experience using the Youth Smoking Survey (YSS) school smoking profile to inform and improve future knowledge exchange strategies with schools. Methods: This study employed a two-phase, sequential explanatory mixed method approach. Phase One consisted of a close-ended mail-out questionnaire to 111 school administrators who had not viewed their schools’ feedback report. Phase Two consisted of telephone interviews with consenting questionnaire participants. Results: Of the 111 eligible schools, 71% (N=79) responded to the questionnaire; 29 school administrators participated in the follow-up interviews. Overall, questionnaire respondents rated the feedback report’s layout very positively in terms of clarity and relevancy, but somewhat less positively on timeliness and level of detail (too much). The majority of school administrators (82%) plan to use the feedback report when planning programs, curriculum, or events, and would primarily discuss the report with teachers, students, and parents. While interview participants provided positive feedback regarding the communication quality, relevance, timeliness, and content of the smoking profile, further investigation revealed a weak relationship between these information characteristics and knowledge use (conceptual and instrumental). The weak association could be attributed to the small sample (N=29), the fact that participants had not previously viewed their feedback reports, and did not have adequate time to incorporate the findings into their practice. Conclusions: The findings have contributed to our understanding of the knowledge utilization process of school administrators. Specifically, it examined how end users perceived source and information characteristics in school smoking profile, and the extent conceptual and instrumental knowledge use are associated with the these characteristics. Findings will guide profile revisions and process.

As the Canadian population ages, the burden on our community and health care systems of age-related conditions, such as dementia, is increasing and research in these areas is becoming more critical. Dementia is a major health concern for adults as they age. Although dementia is the most common neurological disease in older adults, headaches are the most common neurological disorder across all ages. Migraines are a common form of headache disorders that affect millions of people worldwide. Both neurological disorders—dementia and migraines—cause significant impairment for the individual and strain on their caregivers, as well as substantial economic impact on society. The relationship between migraines and late-life cognitive health outcomes has not yet been thoroughly explored. Using data from the Manitoba Study of Health and Aging (MSHA), the relationship between migraines and various late-life cognitive health outcomes, including overall dementia, Alzheimer’s disease (AD), vascular dementia (VaD) and cognitive impairment-no dementia (CIND), was examined. As migraines and cognitive impairments are often associated with various comorbid disorders, analyses also investigated the impact of possible associated intervening variables: hypertension, diabetes, stroke, myocardial infarction and other heart conditions. A secondary focus of this project was to examine whether the association between migraines and late-life cognitive health outcomes varied by sex and family history of dementia. Migraines were a significant risk factor for both overall dementia and AD. However, the relationship between migraines and overall dementia appeared to be driven by the significant relationship between migraines and AD. Having a history of migraines was not significantly related to VaD. However, stroke was a statistically significant intervening variable in the relationship between migraines and VaD, indicating that the vascular event, stroke, plays an important part in the migraine-VaD relationship. A history of migraines was not a significant risk factor for CIND. Results could not be stratified by sex because of all participants with migraines, no men developed dementia and only one man developed CIND. Furthermore, despite a lack of significant results from models stratified by family history of dementia, the results are suggestive of possible genetic influences in the relationship between migraines and AD. Overall, this study supports the conclusion that migraines are a significant risk factor for late-life cognitive health, specifically AD. In addition, this study highlights the possibility that vascular events, such as stroke, may play an important role in the relationship between migraines and VaD. Increased understanding of mid-life risk factors for late-life cognitive health outcomes has important implications for researchers and clinicians in the form of interventions, preventative treatments and medications. In addition, this study suggests that there is a need for further research regarding possible genetic influences in the relationship between migraines and AD. As it was unable to be fully addressed in this study, future studies should investigate gender differences among individuals with migraines developing late-life cognitive health outcomes. This research aims to help develop new strategies that could aid in the prevention of cognitive decline, improve quality of life, and increase the likelihood of healthy aging.