Honolulu-Asia Aging Study Research Articles

Cross-sectional and longitudinal associations between late-life depressive symptoms and cognitive deficits: 20-year follow-up of the Kuakini Honolulu-Asia aging study

ObjectiveTo examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men. MethodsWe assessed 3,088 dementia-free Kuakini-HAAS participants aged 71–93 (77.1 ± 4.2) years at baseline (1991–1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype. ResultsCross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (β = −0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (β = −0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (β = −0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time. ConclusionPsychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition.

Abstract MP19: Patterns of Early-Onset and Late-Onset Dementia Incidence in the Dementia Risk Pooling Project

Introduction: Early-onset dementia (EOD) is defined as dementia diagnosed before age 65. While much is known about late-onset dementia (LOD), research on EOD is scarce. The Dementia Risk Pooling Project (DRPP) harmonized data from nine community-based prospective studies, including under-represented racial/ethnic groups. We hypothesized that EOD incidence rates are higher for men than women, and non-Hispanic (NH) Black participants than other race/ethnicity groups. Methods: We used data from eight DRPP cohorts: Age, Gene/Environment Susceptibility-Reykjavik Study, Whitehall II study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Honolulu-Asia Aging Study, Multi-Ethnic Study of Atherosclerosis, Sacramento Area Latino Study on Aging, and six Framingham Heart Study cohorts. Individual data were pooled and rigorously harmonized. Race/ethnicity was categorized as self-reported Hispanic, NH White, NH Black, and NH other/unknown. Crude incidence rates and ratios were calculated per 10,000 person-years with 95% confidence intervals. Results: The analytic sample consisted of 56,607 participants, who experienced 7,504 cases of LOD and 124 cases of EOD over a median follow-up of 19.13 (IQR 10.46 - 31.11) years. EOD and LOD incidence rates per 10,000 person-years were 1.95 (95% CI 1.62 - 2.32) and 123.35 (95% CI 120.49 - 126.26), respectively. Compared to women, men had 1.17 (95% CI 0.82 - 1.66) times the rate of EOD but 0.82 (95% CI 0.79 - 0.86) times the rate of LOD. Similarly, compared to NH Whites, Hispanics and participants of other or unknown race/ethnicity had higher rates of EOD but lower rates of LOD. NH Blacks had a higher rate of both EOD and LOD compared to NH Whites, but the association with EOD was more pronounced. Conclusion: In this multi-cohort study with individual participant data, EOD and LOD incidence rates were different across sex and race/ethnicity groups. Some of these differences may be due to longer life expectancy in women and some race/ethnicity groups.

Abstract 68: FOXO3 Longevity Genotype Attenuates the Impact of Hypertension on Microinfarct Risks

Background: The G allele of FOXO3 SNP rs2802292, which is associated with human resilience and longevity, has been shown to attenuate the impact of hypertension on the risk of intracerebral hemorrhage. We sought to determine whether the FOXO3 G -allele similarly attenuates the impact of hypertension on the risk of cerebral microinfarcts (CMI). Methods: From a prospective population-based cohort of American men of Japanese ancestry from the Kuakini Honolulu Heart Program (KHHP) and Kuakini Honolulu-Asia Aging Study (KHAAS) that had brain autopsy data, age-adjusted prevalence of any CMI on brain autopsy was assessed. Logistic regression models, adjusted for age at death, cardiovascular risk factors, FOXO3 and APOE- ε 4 genotypes, were utilized to determine the predictors of any CMI. Interaction of FOXO3 genotype and hypertension was analyzed. Results: Among 809 men with complete data, 511 (63.2%) participants had evidence of CMI. A full multivariable model demonstrated that body mass index (OR=1.07, 95% CI=1.01-1.14, P =0.012) was the only predictor of CMI, while hypertension was a borderline predictor (OR=1.44, 95% CI=1.00-2.08, P =0.052). However, a significant interaction between FOXO3 G -allele carriage and hypertension was observed ( P =0.020). In the stratified analyses, among the participants without the longevity-associated FOXO3 G -allele, hypertension was a strong predictor of CMI (OR=2.25, 95% CI=1.34-3.77, P =0.0021), while among those with the longevity-associated FOXO3 G -allele, hypertension was not a predictor of CMI (OR=0.88, 95% CI: 0.51-1.54, P =0.66). Conclusions: The longevity-associated FOXO3 G -allele mitigates the impact of hypertension on the risk of CMI.

KUAKINI HHP CENTER FOR TRANSLATIONAL RESEARCH ON AGING: LATEST FINDINGS FROM MODEL ORGANISMS TO HUMANS

Abstract Kuakini Medical Center (Kuakini) was funded by NIH in late 2019 to create an interdisciplinary Hawai’i-based, Center of Biomedical Research Excellence (COBRE), for translational research on aging. This Center is building upon Kuakini’s five-decades of prior NIH-funded research. These resources include clinical data from the 58-year ongoing Kuakini Honolulu Heart Program (HHP), Honolulu-Asia Aging Study, HHP Offspring Study and a large biorepository with over 500,000 biological samples. The Center’s overarching aim is to increase infrastructure for collaborative aging research in Hawaii. The first step is to grow the Center’s faculty by hiring and mentoring research project leaders (RPLs) from diverse disciplines to become independent, R01-funded, investigators on aging. Our first RPL has graduated after obtaining R01-funded status. His project utilizes novel CRISPR methods to i) improve the safety and efficacy of delivering potentially therapeutic genes (such as FOXO3) to the mouse genome, and ii) test whether temporal enhancement of FOXO3 expression improves healthy aging in this mouse model - both key steps for potential translation to human clinical therapies. This work will be highlighted in the Program Overview session followed by current RPL findings. These findings include novel findings on a potential relation between FOXO3 genotype and stroke dynamics in elderly Japanese-American males; venous congestion in the brain and its potential impact on cognitive function; new findings on the Okinawan longevity phenomenon, among other interesting findings related to healthy aging. Supported by NIGMS 5P20GM125526 and NIA R01AG027060.

FOXO3 LONGEVITY GENOTYPE AND CEREBROVASCULAR DISEASE

Abstract The influence of the FOXO3-longevity associated genotype on cerebrovascular disease (CVD) is little studied. There are reports of a protective effect against stroke mortality in some populations. But these findings have not been widely replicated, nor have potential mechanisms been identified. This presentation will present recent, novel insights on the relation of FOXO3 genotype to CVD. We studied a cohort of over 800 American men of Japanese ancestry from the Kuakini Honolulu Heart Program (KHHP) and Kuakini Honolulu-Asia Aging Study (KHAAS). This population-based dataset included brain autopsy data and age-adjusted prevalence of various types of CVD, including intracerebral hemorrhage (ICH) and cerebral microinfarcts (CMI). Logistic regression models, adjusted for age at death, cardiovascular risk factors, FOXO3 and APOE-ε4 genotypes, among other risk factors were utilized to determine the predictors of both outcomes. FOXO3 genotype did not directly modify risk for ICH or CMI. However, the FOXO3 longevity genotype had significant interaction (protective) effects against hypertension-associated ICH and CMI. These data suggest that the longevity-associated FOXO3 G-allele mitigates the impact of hypertension on the risk of ICH and CMI. Further research is needed in other populations.

FOXO3 longevity genotype attenuates the impact of hypertension on cerebral microinfarct risk.

The G -allele of FOXO3 SNP rs2802292 , which is associated with human resilience and longevity, has been shown to attenuate the impact of hypertension on the risk of intracerebral hemorrhage (ICH). We sought to determine whether the FOXO3 G -allele similarly attenuates the impact of hypertension on the risk of cerebral microinfarcts (CMI). From a prospective population-based cohort of American men of Japanese ancestry from the Kuakini Honolulu Heart Program (KHHP) and Kuakini Honolulu-Asia Aging Study (KHAAS) that had brain autopsy data, age-adjusted prevalence of any CMI on brain autopsy was assessed. Logistic regression models, adjusted for age at death, cardiovascular risk factors, FOXO3 and APOE-ε4 genotypes, were utilized to determine the predictors of any CMI. Interaction of FOXO3 genotype and hypertension was analyzed. Among 809 men with complete data, 511 (63.2%) participants had evidence of CMI. A full multivariable model demonstrated that BMI [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14, P = 0.015) was the only predictor of CMI, while hypertension was a borderline predictor (OR 1.44, 95% CI 1.00-2.08, P = 0.052). However, a significant interaction between FOXO3 G -allele carriage and hypertension was observed ( P = 0.020). In the stratified analyses, among the participants without the longevity-associated FOXO3 G -allele, hypertension was a strong predictor of CMI (OR 2.25, 95% CI 1.34-3.77, P = 0.002), while among those with the longevity-associated FOXO3 G -allele, hypertension was not a predictor of CMI (OR 0.88, 95% CI 0.51-1.54, P = 0.66). The longevity-associated FOXO3 G -allele mitigates the impact of hypertension on the risk of CMI.

IS CEREBRAL AMYLOID ANGIOPATHY A PRECIPITATING EVENT IN THE ETIOLOGY OF ALZHEIMER’S DISEASE

Abstract Amyloid plaque and cerebral amyloid angiopathy (CAA) are early neuropathologic changes observed in the setting of clinical Alzheimer’s disease (AD), typically preceding biomarker evidence of intraneuronal tau neurofibrillary tangle (NFT) development and associated cognitive decline. Here we apply structural equation models to explore the potential causal associations between amyloid-beta lesions (i.e. plaques and CAA) and NFTs as they affect cognitive performance in the elderly.Brain autopsy data used in this study are from the Honolulu Asia Aging Study (HAAS) of Japanese American men from the state of Hawaii (n=600), and the Nuns Study (NS) of Roman Catholic Sisters largely from the upper midwestern United States (n=378). Cognitive performance within three years of death was assessed by multi-domain dementia rating scales.We found that neocortical neuritic plaque and CAA effects on cognitive performance were mediated by neocortical NFTs for both the HAAS (p < 0.002) and NS (p < 0.043). There were no direct effects of neuritic plaque and CAA after controlling for the mediating effect of NFTs (p > 0.54).These data are consistent with the hypothesis that the association between neuritic plaque and CAA on cognition is mediated by NFT load. This may inform our understanding of the etiology of NFT lesion pathology in aging and AD. The disruption of arterial smooth muscle function by CAA has predictable effects on glymphatic processes and on the regulation of capillary blood flow. These effects are plausibly relevant to the AD neurodegenerative process, and these pathways deserves continued attention by the AD research community.

KUAKINI HHP CENTER FOR TRANSLATIONAL RESEARCH ON AGING: LATEST FINDINGS FROM MICE TO HUMANS

Abstract Kuakini Medical Center (Kuakini) was funded by NIH in late 2019 to create an interdisciplinary Hawai’i-based, Center of Biomedical Research Excellence (COBRE), for translational research on aging. This Center is building upon Kuakini’s five-decades of prior NIH-funded research. These resources include clinical data from the 57-year ongoing Kuakini Honolulu Heart Program (HHP), Honolulu-Asia Aging Study, HHP Offspring Study and a large biorepository. The Center’s overarching aim is to increase infrastructure for collaborative aging research in Hawaii. The first step is to grow the Center’s faculty by hiring and mentoring research project leaders (RPLs) from diverse disciplines to become independent, R01-funded, investigators on aging. Our first RPL has graduated after obtaining R01-funded status. His project utilizes novel CRISPR methods to i) improve the safety and efficacy of delivering potentially therapeutic genes (such as FOXO3) to the mouse genome, and ii) test whether temporal enhancement of FOXO3 expression improves healthy aging in this mouse model - both key steps for potential translation to human clinical therapies. This work will be highlighted in the Program Overview session followed by current RPL findings. The first of these current RPL talks presents data on a potential relation between the FOXO3 gene and vascular dementia in elderly Japanese-American males. The second talk reports on how strong social networks mitigate risk for dementia in elderly Japanese-American males. The third talk will report a relation between FOXO3-associated resilience to hypertension and lower intracerebral hemorrhagic stroke risk in elderly Japanese-American males. Supported by NIGMS 5P20GM125526 and NIA R01AG027060.

LATE-LIFE SOCIAL NETWORKS AND INCIDENT ALZHEIMER'S DISEASE: THE KUAKINI HONOLULU-ASIA AGING STUDY

Abstract 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.

Weak Social Networks in Late Life Predict Incident Alzheimer's Disease: The Kuakini Honolulu-Asia Aging Study.

We assessed 10-year longitudinal associations between late-life social networks and incidence of all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) in Japanese-American men. We prospectively analyzed, from baseline (1991-1993) through 1999-2000, 2636 initially nondemented Kuakini Honolulu-Asia Aging Study participants who remained dementia-free during the first 3 years of follow-up. Global cognition was evaluated by the Cognitive Abilities Screening Instrument (CASI); depressive symptoms by the 11-item Center for Epidemiologic Studies Depression (CES-D) Scale; and social networks by the Lubben Social Network Scale (LSNS). Median split of LSNS scores defined weak/strong social network groups. A panel of neurologists and geriatricians diagnosed and classified dementia; AD and VaD diagnoses comprised cases in which AD or VaD, respectively, were considered the primary cause of dementia. Median (range) baseline age was 77 (71-93) years. Participants with weak (LSNS score ≤29) versus strong (>29) social networks had higher age-adjusted incidence (in person-years) of ACD (12.6 vs. 8.7; p = .014) and AD (6.7 vs. 4.0; p = .007) but not VaD (2.4 vs. 1.4; p = .15). Kaplan-Meier curves showed a lower likelihood of survival free of ACD (log-rank p < .0001) and AD (p = .0006) for men with weak networks. In Cox proportional hazards models adjusting for age, education, APOE ɛ4, prevalent stroke, depressive symptoms, and CASI score (all at baseline), weak networks predicted increased incidence of ACD (hazard ratio [HR] = 1.52, p = .009) and AD (HR = 1.67, p = .014) but not VaD (p > .2). Weak social networks may heighten the risk of dementia and AD, underscoring the need to promote social connectedness in older adults.

Mid- and later-life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility-Reykjavik Study.

Dementia prediction models are necessary to inform the development of dementia risk reduction strategies. Here, we examine the utility of neuropathological-based risk scores to predict clinical dementia. Models were developed for predicting Alzheimer's disease (AD) and non-AD neuropathologies using the Honolulu Asia Aging neuropathological sub-study (HAAS; n = 852). Model accuracy for predicting clinical dementia, over 30 years, was tested in the non-autopsied HAAS sample (n = 2960) and the Age, Gene/Environment Susceptibility-Reykjavik Study (n = 4614). Different models were identified for predicting neurodegenerative and vascular neuropathology (c-statistic range: 0.62 to 0.72). These typically included age, APOE, and a blood pressure-related measure. The neurofibrillary tangle and micro-vascular lesion models showed good accuracy for predicting clinical vascular dementia. There may be shared risk factors across dementia-related lesions, suggesting common pathways. Strategies targeting these models may reduce risk or postpone clinical symptoms of dementia as well as reduce neuropathological burden associated with AD and vascular lesions.

A 13-Year Time-Lagged Description of General Cognitive and Functional Abilities in Older Men: A Cross-Lagged Panel Model.

Objectives: The purpose of this study was to evaluate a cross-lagged panel model of general cognition and functional abilities over 13years. The goal was to determine whether general cognitive abilities predict or precede functional decline versus functional abilities predicting cognitive decline. Methods: The sample included 3508 men (71-93years of age at baseline) of the Kuakini Honolulu-Asia Aging Study who were tested repeatedly using a global cognitive test and an assessment of functional capacity. Education and age served as covariates. Cross-lagged models were tested, assessing stationarity of stability and cross-lags. Results: The overall model fit the data well. Cognitive scores had better stability than functional abilities and predicted functional abilities more strongly than functional abilities predicted cognitive scores over time. The strength of all cross-lags increased over time. Discussion: These longitudinal data show that cognitive scores predicted functional decline in a population-based study of older men.

Midlife alcohol consumption and later life cognitive impairment: Light drinking is not protective and APOE genotype does not change this relationship.

IntroductionMuch debate exists about the role of light to moderate alcohol intake and subsequent cognitive function. The apolipoprotein E genotype may modify the relationship.MethodsUsing data from the Honolulu-Asia Aging Study, a longitudinal population-based cohort (n = 2,416), Cox proportional hazards regression analyses were performed to measure midlife alcohol intake (average age = 52 years) and later life cognitive function (average age = 87 years) and to explore the role of apolipoprotein E genotype.ResultsNo protective effect of light drinking (>1 drink/month– 1 drink/day) or moderate drinking (>1–2 drinks/day) was observed in the cohort in adjusted models (HR = 1.013, CI:0.88–1.16; HR = 1.104, CI:0.91–1.34, respectively). Heavy drinking (>2–4 drinks/day) and very heavy drinking (>4 drinks/day) increased the risk for incident moderate cognitive impairment (HR = 1.355, CI:1.09–1.68; HR = 1.462, CI:1.04–2.05, respectively). When examining the relationship by apolipoprotein E ε4 carrier status, a similar dose-response pattern was observed in both groups with higher hazard ratios for those carrying at least one copy of the apolipoprotein E ℇ4 allele. As alcohol level increased, the age at incident moderate cognitive impairment decreased, especially among those with at least one apolipoprotein E ℇ4 allele.DiscussionWe did not observe a significant protective effect for light to moderate drinking in midlife and subsequent cognitive impairment in this cohort. Heavy drinking increased the risk for moderate cognitive impairment and decreased the age at incidence, as did carrying at least one allele of the apolipoprotein E ℇ4 gene.

Predicting Parkinson's Disease and Its Pathology via Simple Clinical Variables.

Background:Parkinson’s disease (PD) is a chronic, disabling neurodegenerative disorder.Objective:To predict a future diagnosis of PD using questionnaires and simple non-invasive clinical tests.Methods:Participants in the prospective Kuakini Honolulu-Asia Aging Study (HAAS) were evaluated biannually between 1995–2017 by PD experts using standard diagnostic criteria. Autopsies were sought on all deaths. We input simple clinical and risk factor variables into an ensemble-tree based machine learning algorithm and derived models to predict the probability of developing PD. We also investigated relationships of predictive models and neuropathologic features such as nigral neuron density.Results:The study sample included 292 subjects, 25 of whom developed PD within 3 years and 41 by 5 years. 116 (46%) of 251 subjects not diagnosed with PD underwent autopsy. Light Gradient Boosting Machine modeling of 12 predictors correctly classified a high proportion of individuals who developed PD within 3 years (area under the curve (AUC) 0.82, 95%CI 0.76–0.89) or 5 years (AUC 0.77, 95%CI 0.71–0.84). A large proportion of controls who were misclassified as PD had Lewy pathology at autopsy, including 79%of those who died within 3 years. PD probability estimates correlated inversely with nigral neuron density and were strongest in autopsies conducted within 3 years of index date (r = –0.57, p < 0.01).Conclusion:Machine learning can identify persons likely to develop PD during the prodromal period using questionnaires and simple non-invasive tests. Correlation with neuropathology suggests that true model accuracy may be considerably higher than estimates based solely on clinical diagnosis.

Methods used in 'ALDH2*2 association with longevity and reduced risk of cognitive decline in Japanese-American men'

ALDH2*2 is a loss of function mutation common in East Asian populations associated with facial flushing on exposure to alcohol and increased risk of certain cancers. Conversely, absence of the ALDH2*2 mutation is associated with increased risk of hypertension and cerebral microbleeds, and two recent studies report a higher frequency of ALDH2*2 alleles in nonagenarians compared to population control samples. We used survival analysis to investigate the association between ALDH2*2 and risk of cognitive impairment and death after controlling for midlife alcohol consumption and other covariates. Participants are 621 Japanese-American men (72 to 92) enrolled in the Honolulu Asia Aging Study (HAAS) and assessed for cognitive impairment for up to 20 years. Impairment was defined as crossing below a threshold score of 74 on the Cognitive Assessment Screening Instrument (CASI). Age at death was determined by Hawaii state death certificate. Ounces of ethyl alcohol consumed per month was assessed by structured interview (number, frequency, and type of beverage) conducted 25 years prior to baseline cognitive assessment. Persons heterozygous for the ALDH2*2 variant have reduced risk of cognitive impairment and reduced risk of death, compared to homozygote non-carriers. Covarying by alcohol exposure had no effect on observed associations. This study replicates previous findings associating ALDH2*2 with longevity, and provides evidence the protective effect extends to cognition. This poster details the statistical analysis carried out to obtain these results.

Kuakini HHP Center for Translational Research on Aging: Aims and Preliminary Findings

Kuakini Medical Center (Kuakini) is creating an interdisciplinary Hawai’i-based Center for translational research on aging. This Center will build upon Kuakini’s five-decades of NIH-funded research, its 420,000-specimen biorepository, and existing strengths in aging research, notably, the 56-year ongoing Kuakini Honolulu Heart Program cohort study (Kuakini HHP), Kuakini Honolulu-Asia Aging Study (Kuakini HAAS), and Kuakini HHP Offspring Study. The overall goal is to find practical means to enhance healthy human lifespan (healthspan). Four research project leaders (RPLs) have been selected from various disciplines for mentorship in translational aging research. The first RPL presentation will introduce a novel mouse model, enabling controlled expression of the pro-longevity gene FoxO3, and assess the impact on lifespan and healthspan phenotypes in mice. These phenotypes will be compared to similar phenotypes in humans with/without the FOXO3 longevity genotype. The second RPL presentation will assess the relation between leukocyte telomere attrition rates (from banked blood collected at three time points over 20-plus years) in older Kuakini HHP men with/without the FOXO3 longevity genotype. The third RPL presentation will assess whether FOXO3 genotype, peripheral leukocyte telomere dynamics (attrition rate, telomerase activity) and inflammatory cytokines mediate the human brain integrity and function with age. This project will utilize structural and functional MRI data from male and female Kuakini HHP Offspring Study participants. The fourth RPL presentation will assess whether APOE e2, e4, and FOXO3 longevity-associated alleles impact 34-year incidence of intracerebral hemorrhage. We will summarize the findings, address the healthspan implications and provide future directions. Supported by NIH 5P20GM125526.

The Origins of the Protein Spread in Parkinson's Disease.

The Origins of the Protein Spread in Parkinson's Disease.

Cross-ethnic comparison of the association between central sleep apnea and atrial fibrillation/flutter: The Kuakini Honolulu-Asia Aging Study and the Osteoporotic Fractures in Men (Mr.OS) study.

IntroductionFew studies indicated the impact of ethnicity on an association between central sleep apnea (CSA) and atrial fibrillation/flutter (AF) in older populations. We assessed possible ethnic differences in the association among elderly Japanese-American and White-American men.MethodsWe performed a cross-sectional analysis using two population studies of Japanese-American and White-American men. The Kuakini Honolulu-Asia Aging Study is a longitudinal cohort study of Japanese-American men living in Hawaii. Sleep data were collected between 1999 and 2000. The Osteoporotic Fractures in Men (Mr.OS) Sleep Study was conducted between 2003 and 2005 on the continental U.S. The majority of Mr.OS participants were White-American. We selected 79–90 year old males, who had overnight polysomnography from both studies. Total participants were 690 Japanese-American and 871 White-American men. The central apnea index (CAI) was the measure of the number of central apneas. CSA was defined by CAI>=5. Cheyne-Stokes breathing (CSB) was defined as a minimum consecutive 5–10 min period of a crescendo-decrescendo respiratory pattern associated with CSA.ResultsThe prevalence of AF was 5.7% in Japanese-American men and 9.0% in White-American men. The prevalence of CSA and CSB in White-Americans were higher than in Japanese-Americans (11.5% vs 6.5% and 5.7% vs 3.3%, respectively). In multivariable-adjusted logistic regression models, CSA was associated with higher odds of AF, and the association was stronger in Japanese-Americans [Odds Ratio (OR) = 4.77, 95% confidence interval (CI): 1.95–11.67] than in White-Americans (OR = 2.09, 95 %CI: 1.09–4.01). CSB showed similar trends as CSA.ConclusionsAfter adjustment, CSA and CSB were significantly associated with AF in both Japanese-American and White-American men.

396 Ethnicity modifies the association between central sleep apnea and atrial fibrillation in older men: Kuakini HAAS and Mr.OS

Abstract Introduction Several studies indicated there is an association between central sleep apnea (CSA) and atrial fibrillation (AF) in older populations. However, few studies assessed the impact of ethnicity on the association. We assessed the hypothesis that ethnicity modifies the association between CSA and AF in older men. Methods We did a cross-sectional analysis using two population studies of Japanese-American (JA) and White-American (WA) men. The Kuakini Honolulu-Asia Aging Study (HAAS) is a longitudinal cohort study of JA men living in Hawaii. Sleep data were collected between 1999–2000. The Osteoporotic Fractures in Men (Mr.OS) Sleep Study was conducted between 2003–2005 on the continental U.S. The majority of Mr.OS participants were WA. We selected 79–90 year old males, who had overnight polysomnography from both studies. Total participants were 690 JA and 871 WA men. Obstructive apnea-hypopnea index (OAHI) was the measure of the number of obstructive apneas and hypopneas with &amp;gt;4% oxygen desaturation. Additionally, the central apnea index (CAI) was the measure of the number of central apneas. Obstructive sleep apnea (OSA) was categorized as none (OAHI &amp;lt;5), mild (OAHI 5–14), moderate (OAHI 15–29), and severe (OAHI&amp;gt;=30). CSA was defined by CAI&amp;gt;=5. Cheyne-Stokes breathing (CSB) was defined as a minimum consecutive 5–10 minute period of a crescendo-decrescendo respiratory pattern associated with CSA. A board-certified physician confirmed AF by single lead electrocardiography of polysomnography. Results The prevalence of AF was 5.7% in JA and 9.1% in WA. The prevalence of CSA and CSB in WA were higher than in JA (11.5% vs 6.5% and 5.7% vs 3.3%, respectively). Conversely, the prevalence of severe OSA in JA (20.7%) was higher than in WA (11.8%). In multivariable-adjusted logistic regression models, CSA was associated with higher odds of AF, and the association was stronger in JA [Odds Ratio (OR)=4.77, 95% confidence interval (CI): 1.95–11.64] than in WA (OR=2.05, 95% CI: 1.07–3.94). CSB showed similar trends as CSA. In contrast, the severity of OSA was not significantly associated with AF in either ethnicity. Conclusion Ethnicity modifies the association between CSA and AF. In older JA and WA men, screening for CSA might be important to prevent AF. Support (if any):

Factors Associated with Lower Cognitive Performance Scores Among Older Japanese Men in Hawaii and Japan.

Few studies have compared factors related to cognitive function among people with similar genetic backgrounds but different lifestyles. We aimed to identify factors related to lower cognitive scores among older Japanese men in two genetically similar cohorts exposed to different lifestyle factors. This cross-sectional study of community-dwelling Japanese men aged 71-81 years included 2,628 men enrolled in the Kuakini Honolulu-Asia Aging Study based in Hawaii and 349 men in the Shiga Epidemiological Study of Subclinical Atherosclerosis based in Japan. We compared participant performance through Cognitive Abilities Screening Instrument (CASI) assessment in Hawaii (1991-1993) and Japan (2009-2014). Factors related to low cognitive scores (history of cardiovascular disease, cardiometabolic factors, and lifestyle factors) were identified with questionnaires and measurements. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) of a low (< 82) CASI score based on different factors. CASI scores were lower in Hawaii than in Japan [21.2%(n = 556) versus 12.3%(n = 43), p < 0.001], though this was not significant when adjusted for age and educational attainment (Hawaii 20.3%versus Japan 17.9%, p = 0.328). History of stroke (OR = 1.65, 95%confidence interval = 1.19-2.29) was positively associated with low cognitive scores in Hawaii. Body mass index ≥25 kg/m2 tended to be associated with low cognitive scores in Japan; there was a significant interaction between the cohorts. Cognitive scores differences between cohorts were mostly explained by differences in educational attainment. Conversely, cardiovascular diseases and cardiometabolic factors differentially impacted cognitive scores among genetically similar older men exposed to different lifestyle factors.