FOXO3 LONGEVITY GENOTYPE MITIGATES THE IMPACT OF HYPERTENSION ON RISK OF INTRACEREBRAL HEMORRHAGE

Abstract The longevity-associated FOXO3 G allele of SNP rs2802292 is associated with protection against mortality, however the impact of FOXO3 genotype on the association between hypertension and risk of intracerebral hemorrhage (ICH) has not been assessed. Therefore, we utilized the Kuakini Honolulu Heart Program (KHHP), a prospective population-based cohort of Japanese American men living in Hawaii that began in 1965 to study this relation. After excluding baseline prevalent stroke and those missing FOXO3 data, 6,469 men were included in the analysis. Age-adjusted prevalence of ICH by hypertension was assessed for the whole cohort after stratifying by FOXO3 genotype. Cox regression models, adjusted for age, cardiovascular risk factors, FOXO3 and APOE genotypes, were utilized to assess relative risk of hypertension on ICH. All models were created for the whole cohort and stratified by FOXO3 genotype, namely G allele carriers versus TT genotype. Overall, 183 subjects developed ICH over the 34-year follow-up period. Age-adjusted ICH prevalence was 0.90 versus 1.32 per 1,000 person-years follow-up in those without and with hypertension, respectively (p=0.002). After stratifying by FOXO3 genotype, this association was no longer significant in G allele carriers. In the whole cohort, hypertension was an independent predictor of ICH (RR=1.70, 95%CI 1.25, 2.32; p=0.0007). In stratified analyses, hypertension remained an independent predictor of ICH among the FOXO3 TT allele group (RR=2.02, 95% CI 1.33, 3.07; p=0.001), but not in FOXO3 G allele carriers (RR=1.39, 95% CI 0.88, 2.19; p=0.15). Thus, the longevity/resilience-associated FOXO3 G allele may mitigate the impact of hypertension on ICH risk in this population. Further study is needed in other populations.


FOXO3-MEDIATED PROTECTION AGAINST VASCULAR DEMENTIA RISK IN A CASE-CONTROL STUDY OF ASIAN AMERICAN MEN
Philip Davy 1 , Kalpana Kallianpur 2 , Randi Chen 1 , Timothy Donlon 1 , Brian Morris 1 , Richard Allsopp 3 , Bradley Willcox 1 , and Kamal Masaki 1 , 1. Kuakini Medical Center,Honolulu,Hawaii,United States,2. Kuakini Medical Center,Honolulu,Hawaii,Honolulu,Hawaii,United States,3. University of Hawaii,Honolulu,Hawaii,United States The longevity-associated allele of FOXO3 is associated with a significant reduction in cardiovascular disease (CVD) risk in older adults. We hypothesized that dementia, which shares several risk factors with CVD, might also be related to FOXO3 genotype, particularly vascular dementia (VaD). Therefore, we utilized the Kuakini Honolulu Heart Program/ Honolulu Asia Aging Study dataset to assess the relation of FOXO3 genotype to dementia risk. Preliminary analyses suggested that VaD had the strongest relation to FOXO3 genotype. Therefore, we performed larger, more detailed study of FOXO3 genotype and VaD risk in a 9-year nest case-control study. Chi-Square test was used to assess the association of dementia with FOXO3 genotype in a sample of 1504 Japanese-American male study participants, aged 71-93 years, at the baseline exam. General Linear Model was utilized to compare VaD risk factors between VaD cases and controls. Multivariate Logistic Regression was used to assess the association of VaD with FOXO3 genotype adjusting for birth year, education, APOE4 and other vascular risk factors. We found a significant protective association for carriers of the principal FOXO3 longevity-associated allele (SNP rs2802292 G allele-carriers) against VaD risk (OR = 0.66, 95% CI = 0.44-0.98, p = 0.0388). The protective association retained significance when controlling for common risk factors for VaD in a multivariate model. These data indicate a potential neuroprotective role for the FOXO3 longevity-associated genotype against vascular dementia. This finding merits validation studies in other cohort studies.

LATE-LIFE SOCIAL NETWORKS AND INCIDENT ALZHEIMER'S DISEASE: THE KUAKINI HONOLULU-ASIA AGING STUDY
Kalpana Kallianpur 1 , Kamal Masaki 2 , Randi Chen 2 , Bradley Willcox 2 , Richard Allsopp 3 , Philip Davy 2 , and Hiroko Dodge 4 , 1. Kuakini Medical Center,Honolulu,Hawaii,Honolulu,Hawaii,United States,2. Kuakini Medical Center,Honolulu,Hawaii,United States,3. University of Hawaii,Honolulu,Hawaii,United States,4. Oregon Health & Science University,Portland,Oregon,United States We assessed longitudinal associations between social networks and incidence of all-cause dementia, Alzheimer's disease (AD) and vascular dementia in Kuakini Honolulu-Asia Aging Study participants over a 10-year follow-up period. Median split of Lubben Social Network Scale (LSNS) scores defined weak/strong social networks among 2636 men who were dementia-free at baseline (median age 77 years) and during the first 3 years. Kaplan-Meier curves showed that those with strong networks at baseline were less likely to develop all-cause dementia (p<0.0001) and AD (p=0.0006); probability of dementia-free survival at 10 years for strong and weak social network groups was 93.8% and 89.0%, respectively. Cox regression models adjusting for age and other baseline factors revealed associations of weak networks with increased risk of all-cause dementia (HR=1.52, 95%CI=1.11-2.08, p=0.009) and AD (HR=1.67, 95%CI=1.11-2.51, p=0.014). As strong social networks may protect against incident dementia and AD, and are associated with other health benefits, prevention of social isolation of older adults should be considered a priority.

FOXO3 LONGEVITY GENOTYPE MITIGATES THE IMPACT OF HYPERTENSION ON RISK OF INTRACEREBRAL HEMORRHAGE
Kazuma Nakagawa 1 , Randi Chen 1 , Steven Greenberg 2 , Webster Ross 3 , BRADLEY WILLCOX 1 , Timothy Donlon 1 , Brian Morris 1 , and Kamal Masaki 1 , 1. Kuakini Medical Center,Honolulu,Hawaii,United States,2. Massachusetts General Hospital,Boston,Massachusetts,United States,3. Pacific Health Research and Education Institute,Honolulu,Hawaii,United States The longevity-associated FOXO3 G allele of SNP rs2802292 is associated with protection against mortality, however the impact of FOXO3 genotype on the association between hypertension and risk of intracerebral hemorrhage (ICH) has not been assessed. Therefore, we utilized the Kuakini Honolulu Heart Program (KHHP), a prospective population-based cohort of Japanese American men living in Hawaii that began in 1965 to study this relation. After excluding baseline prevalent stroke and those missing FOXO3 data, 6,469 men were included in the analysis. Ageadjusted prevalence of ICH by hypertension was assessed for the whole cohort after stratifying by FOXO3 genotype. Cox regression models, adjusted for age, cardiovascular risk factors, FOXO3 and APOE genotypes, were utilized to assess relative risk of hypertension on ICH. All models were created for the whole cohort and stratified by FOXO3 genotype, namely G allele carriers versus TT genotype. Overall, 183 subjects developed ICH over the 34-year follow-up period. Age-adjusted ICH prevalence was 0.90 versus 1.32 per 1,000 person-years follow-up in those without and with hypertension, respectively (p=0.002). After stratifying by FOXO3 genotype, this association was no longer significant in G allele carriers. In the whole cohort, hypertension was an independent predictor of ICH (RR=1.70, 95%CI 1.25, 2.32; p=0.0007). In stratified analyses, hypertension remained an independent predictor of ICH among the FOXO3 TT allele group (RR=2.02, 95% CI 1.33, 3.07; p=0.001), but not in FOXO3 G allele carriers (RR=1.39, 95% CI 0.88, 2.19; p=0.15). Thus, the longevity/resilience-associated FOXO3 G allele may mitigate the impact of hypertension on ICH risk in this population. Further study is needed in other populations.

NARRATIVE AS A BOUNDARY CONCEPT IN GERONTOLOGY: THE STORY BEHIND THE STORIES Chair: Kate de Medeiros Co-Chair: Desmond O'Neill
Ever since the "narrative turn" was taken up by the humanities and social sciences in the 1980s and early 1990s, there has been an increased interest in narrative as a medium for gaining knowledge in gerontology. Narrative gerontology in particular assumes that the "life lived is inseparable from the life told" (Bruner 1987). Central to this notion is the metaphor of life as story or, as Kenyon and Randall put it, "[W]e not only have stories, we are stories" (1999). As a boundary concept, "narrative" inhabits several disciplinary worlds. Its analysis can focus on individual identification strategies, on the storytelling process and its context, or on aesthetic dimensions, for instance when analyzing cultural representations including film and fiction. Often loosely defined yet broadly applied, narrative work can range from personal life stories to master narratives that convey cultural and/or political values. The purpose of the Humanities and Arts symposium is to take a critical look at "narrative" within gerontology to include mapping the uses of narrative as actions, objects, ways of knowing and acts of resistance. The first paper presents a conceptual structure of narrative based on findings from a guided review of narrative definitions and approaches in gerontology. The second argues for the normative importance in studying cultural narratives of dementia. The third paper examines narrative in the context of the medical humanities and narrative medicine, pointing to ways in which narrative competence translates into medical practice. The final paper considers the narrative of aging through music.

HOW HAS NARRATIVE BEEN USED IN GERONTOLOGY?: FINDINGS FROM A QUALITATIVE EVIDENCE SYNTHESIS Kate de Medeiros, Miami University, Oxford, Ohio, United States
Narrative gerontology emerged as a concept in the 1990s to describe the ways that people age biographical as well as biologically. Since then, narratives and narrative approaches have gained popularity as methods and ways of knowing. This paper presents findings from a qualitative evidence synthesis (QES) of narrative within the gerontological literature. ). QES describes methods to systematically review qualitative evidence (e.g., extracted text). The purpose is to gain a deeper understanding of a concept rather than evaluate study designs or findings. An initial search returned 1,480 papers. Upon further analysis, the following three large categories with regards to narrative were identified: definitions, accounts, processes, and possibilities. Overall, findings provide an comprehensive overview of uses of narrative within gerontology. Desmond O'Neill, Trinity College Dublin, Dublin, Dublin, Ireland With increasing interest in exploring narratives of aging through literary/oral sources, a less prominent area of inquiry has been possibilities afforded by narratives inherent in music across the life-span and into later-life. Two possible areas of interest are the arc of development and change over the life-course, and inherent content of the music. The latter element is less prominent in narrative analysis, providing a potentially rich field of discovery. While popular song parallels these possibilities, further opportunities arise from instrumental, orchestral and operatic music, allied to strengths in musicological analysis. Later compositions whose elements provide insights into life course review (Shostakovich Viola Sonata and Metamorphosen, Richard Strauss) as well as romantic love in later life across generations (The Cunning Little Vixen, Leos Janáček). The analysis will seek to delineate to possible avenues of interpretation of musicological analysis in understanding the phenomenology and opportunities arising from aging.

UNDERSTANDING CULTURAL NARRATIVES OF DEMENTIA: TASKS AND TOOLS FOR HUMANITIES SCHOLARSHIP Nancy Berlinger, The Hastings Center, Garrison, New York, United States
Humanities scholarship on dementia has long focused on the depiction of dementia in literature, film, and other genres. Recent research on neurodiversity includes humanistic scholarship on creativity within dementia. It is time for interdisciplinary humanities scholarship to focus on narratives of dementia that circulate within aging societies, are embedded in policy, and shape experiences of typical people living with dementia or providing dementia care. This paper argues for the normative importance of studying values-laden cultural narratives, recognizing competing or evolving narratives within a society, and demonstrating how to reframe flawed narratives beyond necessary attention to ageist and ableist language. It presents examples of approaches to social narrative analysis; describes tools and training that could be integrated into humanities scholarship on dementia and aging, and considers the potential role of social narrative analysis in articulating and launching policy ideas for aging societies.

NARRATIVE MEDICINE AS INTERDISCIPLINARY PRACTICE
Ulla Kriebernegg, University of Graz, Graz, Steiermark, Austria When dealing with patients who talk about their illnesses, medical doctors need to interpret the stories they hear. Also, they need to make sense of their own experiences regarding