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Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40-49 years at baseline (2002-2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007-2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS=10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 personyears, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men. [ABSTRACT FROM AUTHOR]

BACKGROUND Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid–femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men. METHODS A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002–2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders. RESULTS Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA. CONCLUSIONS High levels of EPA observed in Koreans have an inverse association with aortic stiffness. [ABSTRACT FROM PUBLISHER]

Background: Mortality from coronary heart disease (CHD) in women in Japan is one of the lowest in developed countries. In an attempt to shed some light on possible reasons of lower CHD in women in Japan compared with the United States, we extensively reviewed and analyzed existing national data and recent literature. Methods: We searched recent epidemiological studies that reported incidence of acute myocardial infarction (AMI) and examined risk factors for CHD in women in Japan. Then, we compared trends in risk factors between women currently aged 50-69 years in Japan and the United States, using national statistics and other available resources. Results: Recent epidemiological studies have clearly shown that AMI incidence in women in Japan is lower than that reported from other countries, and that lipids, blood pressure (BP), diabetes, smoking, and early menopause are independent risk factors. Comparing trends in risk factors between women in Japan and the United States, current levels of serum total cholesterol are higher in women in Japan and levels have been similar at least since 1990. Levels of BP have been higher in in Japan for the past 3 decades. Prevalence of type 2 diabetes has been similar in Japanese and white women currently aged 60-69 for the past 2 decades. In contrast, rates of cigarette smoking, although low in women in both countries, have been lower in women in Japan. Conclusions: Differences in risk factors and their trends are unlikely to explain the difference in CHD rates in women in Japan and the United States. Determining the currently unknown factors responsible for low CHD mortality in women in Japan may lead to new strategy for CHD prevention. [ABSTRACT FROM AUTHOR]

Objective. Despite considerable study, the relevance of leptin and adiponectin for atherosclerosis development is still unsettled. We investigated relations of serum leptin and adiponectin to serum C-reactive protein (CRP), using the INTERLIPID dataset on Japanese emigrants living in Hawaii and Japanese in Japan. Design and Methods. Serumleptin, adiponectin, and CRP were measured by standardized methods in men and women of ages 40 to 59 years from two population samples, one Japanese-American in Hawaii (83 men, 89 women) and the other Japanese in central Japan (111 men, 104 women). Participants with CRP >10mg/L were excluded. Results. Sex-specific multiple linear regression analyses, with log-transformed leptin and adiponectin (log-leptin, log-adipo), site (Hawaii = 1, Japan = 0), SBP, HbA1c, smoking (cigarettes/day), and physical activity index score of the Framingham Offspring Study as covariates, showed that log-leptin directly related and log-adipo inversely related to log-CRP for both sexes (Ps < 0.05 to <0.01). Addition to the model of BMI and interaction terms (BMI × log-leptin, BMI × log-adipo, SITE × log-leptin, SITE × logadipo) resulted in disappearance of statistical significance except for direct relation of log-leptin to log-CRP in men (P = 0.006). Conclusions. Leptin directly related to CRP independent of BMI and other confounding factors in men but not in women. [ABSTRACT FROM AUTHOR]

While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>277.5 mg/d) were less likely than men in the lowest quartile (≤115.5 mg) to have any of the lesion types (adjusted-OR, 0.45; 95% CI, 0.23-0.89; p, trend = 0.04). Coffee and caffeine intake in midlife were not associated with cognitive impairment, dementia, or individual neuropathologic lesions, although higher caffeine intake was associated with a lower odds of having any of the lesion types at autopsy. [ABSTRACT FROM AUTHOR]

Introduction. Hypertension and cigarette smoking are dominant risk factors for cardiovascular disease in Japan while in westernized countries, broader effects encompass obesity, diabetes, and hypercholesterolemia. This paper examines whether different associations also appear important in the manifestation of activities of daily living (ADL) in older Japanese men in Hawaii and Japan. Methods. Measures of ADL (feeding, toileting, dressing, bathing, and walking around the house) were assessed from 1995 to 1999 in 1,893 men in Hawaii and 543 men in Japan. Concomitant risk factors were measured from 1990 to 1993. Results. In Hawaii, diabetes increased the odds of ≥1 ADL impairment nearly 1.5-fold (P = .020). A similar association was absent in Japan. In contrast, the odds of an ADL impairment in Japan was increased more than 5-fold in the presence of stroke (P < .001). The association in Hawaii was significantly weaker (P = .007). In both cohorts, past alcohol use was associated with a greater likelihood of ADL impairment. Conclusion. In this comparison of genetically similar samples, findings suggest that different strengths in risk factor associations with cardiovascular disease in Japan and westernized countries may also include different strengths in associations with impaired ADL. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the reliability and correlations with age of the balance components of the EPESE, NHANES, and the Good Balance Platform System (GBPS) in a normal population of adults. Design. Cross-sectional. Setting. UrbanMedical Center in the Pacific. Participants. A random sample of 203 healthy offspring of Honolulu Heart Program participants, ages 38-71. Measurements. Subjects were examined twice at visits one week apart using the balance components of the EPESE, NHANES, and the good balance system tests. Results. The EPESE and NHANES batteries of tests were not sufficiently challenging to allow successful discrimination among subjects in good health, even older subjects. The GBPS allowed objective quantitative measurements, but the test-retest correlations generally were not high. The GBPS variables correlated with age only when subjects stood on a foam pad; they also were correlated with anthropometric variables. Conclusion. Both EPESE and NHANES balance tests were too easy for healthy subjects. The GBPS had generally low reliability coefficients except for themost difficult testing condition (foam pad, eyes closed). Both height and body fat were associated with GBPS scores, necessitating adjusting for these variables if using balance as a predictor of future health. [ABSTRACT FROM AUTHOR]

Background: Arthritis is the most common chronic disease in the elderly. Studies show that rheumatoid arthritis is a risk factor for cardiovascular morbidity and mortality, and osteoarthritis is associated with an unfavorable cardiovascular risk factor profile. Methods: A/the Honolulu Heart Program's fourth examination in 1991 to 1993, arthritis smuts was assessed among a cohort of 3741 Japanese-American males, ages 71 to 93 years. Arthritis was determined by self-report of physician diagnosis, and subjects were divided into two groups: current arthritis and no current arthritis. Eight years of follow-up data are available for incident coronary heart disease (CHD) in 2777 subjects free of CHD at baseline. Age-adjusted rates of incident CHD and means of cardiovascular risk factors were compared in each group, Cox proportional hazards models were used to calculate relative risks, adjusting for common cardiovascular risk factors, alcohol, and use of aspirin or NSAIDs, or both. Results: There were 279 cases of incident CHD in the cohort over 8 years: in those with arthritis, 11.7% developed incident CHD. compared to 9.8% in those without arthritis (p = 0.24). Age-adjusted rates of incident CHD in those with and without arthritis were 20.5 and 18.0 per 1000 person-years, respectively (p = 0.25), Arthritis was not significantly associated with CHD risk factors. Arthritis was not a significant independent predictor of incident CHD (relative risk. 1.06; 95% CI. 0.74 to 1.51). Conclusions: Arthritis, and most probably osteoarthritis, may not be associated with most CHD risk factors or 8-year incident CHD hi elderly Japanese-American males. [ABSTRACT FROM AUTHOR]

This cross-sectional study focused on pain assessment in a group of older Asian Americans with cancer. Thirty-six participants and their primary nurses were interviewed, and pain intensity was measured using 3 different scales: the Numeric pain intensity 0-10 scale, the Faces expression scale,1 and Visual analog scale (VAS).2 Overall, 56% of participants reported pain. Younger age (65-75 years old) was significantly associated with higher pain intensity (p < 0.05). High correlation was found between the participants' and their nurses' pain intensity ratings (r = 0.69, p < 0.0001). High correlation was also found among different pain intensity scales, with a Spearman correlation coefficient ranging from 0.89 to 0.96 (p < 0.0001), suggesting that they are reliable measures in this population. [ABSTRACT FROM AUTHOR]

The article offers information on Apolipoprotein E ε4 allele genotype and the effect of depressive symptoms on the risk of dementia in men. It is said that Apolipoprotein E ε4 (APOE ε4) allele is a genetic risk factor for Alzheimer's disease. The Honolulu-Asia Aging Study, a population-based cohort study of Japanese American men, is conducted. It is mentioned that since individuals with depressive symptoms and the APOE ε4 allele had an increased risk of dementia, it is suggested that one should be watchful for early signs of dementia in the older person with depression.

We redesigned our medical school's Problem-Based Learning (PBL) curriculum to include a substantial increase in required geriatrics content. Innovations included new PBL health care problems and standardized patients (SPs) throughout the first three years and a new required four-week, fourth-year rotation. We used data from the AAMC Medical School Graduation Questionnaire, the UCLA Geriatrics Knowledge Test and Attitudes Survey and a Geriatrics SP Examination to measure self-efficacy, geriatrics specific knowledge, attitudes and clinical skills before and after these curricular changes. Positive effects on students' self-efficacy, knowledge and skills were demonstrated. Scores on the attitude scale were high before and after implementation. The demonstration of improved educational outcomes will help to validate our curricular changes and guide their future development. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the relationship between low levels of human serum albumin (HSA) and the incidence of coronary heart disease (CHD) in a cohort of elderly Japanese-American men. Using data from the Honolulu Heart Program's fourth examination (1991-1993), HSA levels of 998 Japanese American men aged 71-93 years was compared with plasma levels of fibrinogen, total cholesterol HDL cholesterol, LDL cholesterol triglycerides, diastolic BP, BMI, and fasting blood glucose. HSA was significantly negatively associated with age and fibrinogen, and significantly positively associated with total cholesterol, HDL cholesterol LDL cholesterol triglycerides, diastolic BP, BMI and fasting blood glucose. After adjusting for age, tertiles of HSA were significantly positively associated with total cholesterol, HDL cholesterol and triglycerides, and significantly negatively associated with fibrinogen. Using multivariate stepwise regression, significant correlations were seen between HSA and fibrinogen, cholesterol age, HDL cholesterol and triglycerides, and a borderline correlation was seen with systolic blood pressure. However, the model R-square for all variables was only 0.10. In conclusion, HSA levels are significantly associated with several traditional cardiovascular risk factors, particularly serum lipid levels. [ABSTRACT FROM AUTHOR]

Purpose: Determine acceptance of and compliance with intranasal cobalamin (vitamin B12) replacement therapy. Methods: Veteran subjects were recruited from VA Outpatient facilities in Hawai'i. Information was obtained by interview and medical record review. Subjects received the standard dose of intranasal cobalamin of 500 micrograms intranasally, once a week. A follow-up questionnaire was administered at one and three months of therapy. Results: Thirty-four subjects were enrolled in the study. Ages ranged from 29 to 87 years of age, with a mean age of 68. 6. Ninety-seven percent were men, 59% were Caucasian, and 35% were Asian/Pacific Islanders. At the end of three months, 30 patients had completed the study. Ninety percent preferred the gel over injection. In the subset of subjects with a history of depression, only 60% preferred intranasal gel. Conclusion: Veteran patients tolerated intranasal cobalamin gel well. The majority of patients preferred intranasal over intramuscular injection of vitamin B12. [ABSTRACT FROM AUTHOR]

Ethnic diversity among older patients in Hawai'i is common; yet few data exist concerning the applicability of cognitive testing instruments in non-Caucasian populations. This project aimed to determine the specificity and sensitivity of the IQCODE for the detection of cognitive impairment in a Japanese-American population. Results confirm that the IQCODE is a valuable tool for primary care physicians to detect impairment in this population. [ABSTRACT FROM AUTHOR]

Objectives. This study prospectively describes the relationships between alcohol intake and subsequent cognitive performance among participants in the Honolulu Heart Program (HHP). Methods. Alcohol intake was assessed at Exam III of the HHP, and cognitive performance was measured approximately 18 years later with the Cognitive Abilities Screening Instrument (CASI). Complete information was available 1hr 3556 participants, aged 71 to 93 years al follow-up. Results. In multivariate analyses, the relationship between drinking and later cognitive performance appeared nonlinear, as nondrinkers and heavy drinkers (more than 60 ounces of alcohol per month) had the lowest CASI scores and the highest risks of poor and intermediate CAS1 outcomes. Compared with nondrinkers, the risk of a poor CASI score was lowered by 22% to 40% among men who consumed 1-60 ounces of alcohol per month. Conclusions. We report a positive association between moderate alcohol intake among middle-aged men and subsequent cognitive performance in later life. However, it is possible that the health risks associated with drinking outweigh any potential benefits for many elderly persons. (Am J Public Health. 2000;90: 1254-1259) [ABSTRACT FROM AUTHOR]

We report a case series of 11 patients with excessive sweepstakes participation on initial geriatric consultation in Honolulu. Ten of these patients had dementia, mostly Alzheimer's disease, with Folstein MiniMental Status Exam scores ranging from 17-29/30. Money lost ranged from $6,600 to $200,000-400,000. Physicians need to have a high index of suspicion and the public needs to be educated about simple preventive strategies. [ABSTRACT FROM AUTHOR]

A response by M.A. Espeland, L. Gu, and K.H. Masaki to a letter to the edtor about their article "Association Between Reported Alcohol Intake and Cognition Results from the Women's Health Initiative Memory Study" is presented.

The mechanistic target of rapamycin (mTOR) pathway is pivotal for cell growth and has been implicated in aging, cardiovascular disease, obesity, diabetes and cancer. mTOR signaling is involved in cardiac leptin-mediated cardiac hypertrophy and fibrosis associated with obesity. mTOR is a key component of two multiprotein complexes, mTOR complex 1 and mTOR complex 2. The former is pro-growth and contains a unique protein, raptor. The present study tested for the first time whether genetic variation across the raptor gene (RPTOR) is associated with overweight/obesity, essential hypertension (EHT) and isolated systolic hypertension (ISH). We genotyped 61 common (allele frequency ≥ 0.1) tagging single nucleotide polymorphisms (SNPs) that captured most of the genetic variation across RPTOR in 374 subjects of normal lifespan and 439 subjects with a lifespan exceeding 95 years. Subjects were drawn from the Honolulu Heart Program, a homogeneous population of American men of Japanese ancestry, well characterized for phenotypes relevant to conditions of aging. Hypertension status was ascertained when subjects were 45-68 years old. Statistical evaluation was performed by contingency table analysis, logistic regression and recursive partitioning (RP), which is regarded as amongst the most powerful methods for statistical analysis of large complex sets of genetic information. After analysis of RPTOR genotypes by each statistical approach we found no significant association between genetic variation in RPTOR and either EHT or ISH. For EHT, RP revealed that even the most predictive SNPs (rs4969322 and rs4890052) provided little contribution to correctly assigning individuals to EHT or NT (P=0.22 by Z test). In the case of ISH, RP revealed that only one SNP (rs2589118) made a noticeable contribution, and that this was no better than the contribution from the weakest laboratory/examination variable (overweight/obesity). In contrast, for overweight/obesity, the RP model revealed that RPTOR SNPs significantly enhanced the predictive capacity of the model (P=0.008 by one-tailed Z test). In conclusion, genetic variation across RPTOR is associated with overweight/obesity, but not EHT or ISH in the populations of normal lifespan and of long-lived subjects studied. [ABSTRACT FROM AUTHOR]

A response by the authors to a letter to the editor about their article "Midlife Dietary Intake of Antioxidants and Risk of Late-Life Incident Dementia: The Honolulu-Asia Aging Study" is presented.

Abstract: Congruence between preferred and actual place of death may be an essential component in terminal care. Most patients prefer a home death, but many patients do not die in their preferred location. Specialized (physician, hospice, and palliative) home care visits may increase home deaths, but factors associated with congruence have not been systematically reviewed. This study sought to review the extent of congruence reported in the literature and examine factors that may influence congruence. In July 2009, a comprehensive literature search was performed using MEDLINE, PsychInfo, CINAHL, and Web of Science. Reference lists, related articles, and the past five years of six palliative care journals were also searched. Overall congruence rates (percentage of met preferences for all locations of death) were calculated for each study using reported data to allow cross-study comparison. Eighteen articles described 30%–91% congruence. Eight specialized home care studies reported 59%–91% congruence. A physician-led home care program reported 91% congruence. Of the 10 studies without specialized home care for all patients, seven reported 56%–71% congruence and most reported unique care programs. Of the remaining three studies without specialized home care for all patients, two reported 43%–46% congruence among hospital inpatients, and one elicited patient preference “if everything were possible,” with 30% congruence. Physician support, hospice enrollment, and family support improved congruence in multiple studies. Research in this important area must consider potential sources of bias, the method of eliciting patient preference, and the absence of a single ideal place of death. [Copyright &y& Elsevier]

Magnesium (Mg) deficiency is believed to have adverse cardiovascular consequences that are broad and complex, although an association between dietary Mg intake and the risk of coronary heart disease (CHD) has not been clearly identified. The purpose of this study is to examine the relation between dietary Mg intake and future risk of CHD. Reported findings are based on dietary Mg intake in 7,172 men in the Honolulu Heart Program. Intake of Mg was recorded at baseline examinations that took place from 1965 to 1968 when the men were aged 45 to 68 years. In 30 years of follow-up, 1,431 incident cases of CHD were identified. Within 15 years after dietary assessment, the age-adjusted incidence decreased significantly from 7.3 to 4.0 per 1,000 person-years in the lowest (50.3 to 186 mg/day) versus highest (340 to 1,183 mg/day) quintiles of Mg intake (p <0.001). When adjustments were made for age and other nutrients (singly or combined), there was a 1.7- to 2.1-fold excess in the risk of CHD in the lowest versus highest quintiles (p <0.001). The excess risk ranged from 1.5- to 1.8-fold after further adjustment for other cardiovascular risk factors (p <0.05). Associations between dietary Mg and coronary events occurring after 15 years of follow-up were modest. We conclude that the intake of dietary Mg is associated with a reduced risk of CHD. Whether increases in dietary Mg intake can alter the future risk of disease warrants further study. [Copyright &y& Elsevier]

Examines the relations between cognitive test scores in later life and prior myocardial infarction, coronary artery bypass graft surgery (CABG) and stroke. Assessment of cognitive function using the Cognitive Abilities Screening Instrument; Lack of association between poor test performance and history of CABG.

Background : Previous studies have reported an association between total and differential white blood cell (WBC) counts and incident coronary heart disease (CHD), but data from elderly populations are scarce. The purpose of this study was to examine the association between total and differential WBC counts and incident CHD in an elderly Japanese-American population. Methods : Total and differential WBC counts were examined at a baseline examination from 1991 to 1993 in the Honolulu Heart Program. Subjects were Japanese-American men aged 71–93 years free of CHD at baseline ( N = 2879), who were divided into quartiles of total and differential WBC counts for analysis, and were followed for incident CHD for 8 years. Results : During the follow up period, 279 men developed CHD. Hazard ratio for incident CHD for each quartile of total and differential WBC counts were obtained by Cox regression using the lowest quartile as the reference group. After full adjustment including age, cardiovascular risk factors, chronic diseases and medication use, the hazard ratios in the highest quartiles of total WBC, granulocyte and neutrophil counts were 1.75 (95% confidence interval [CI], 1.18–2.62; P = 0.006), 1.66 (95%CI, 1.11–2.48; P = 0.01), and 1.57 (95%CI, 1.06–2.34; P = 0.03), respectively. No significant associations were found between lymphocyte or monocyte counts and incident CHD. Conclusions : Higher total WBC, granulocyte and neutrophil counts were associated with higher risk of incident CHD in a population of elderly Japanese-American men. Further studies are needed to establish cut-points and treatment options with anti-inflammatory medications. [ABSTRACT FROM AUTHOR]

Island people have long been associated with longevity. In the second century BC, the Chinese emperor Ch'in Shih Huang-ti sent a legion of ships and several thousand men in search of fabled islands of longevity in the seas to the south of China. They never returned with news of discovery Two millennia later, island people are again of interest to longevity researchers. Iceland, Sardinia, Okinawa, and Hawaii are among several islands or island chains that lay claim to long- lived people. In particular, the Japanese island prefecture (state) of Okinawa and the American island state of Hawaii offer some interesting similarities and contrasts in the study of human aging and longevity. Health span and life span appear longer than most of the populations of Japan and the United States, respectively. Both populations have undergone recent generational changes in health and associated risk factors (such as obesity), which are diminishing previous health span and life span advantages. However, there is still persistence of this healthy aging and longevity phenomenon in older generations. The environmental and genetic epidemiology of this healthy aging phenomenon has been explored in two collaborative studies—the Okinawa Centenarian Study (OCS) and the Honolulu Heart Program (HHP). This chapter indicates how healthy human aging and longevity are influenced by both genetic and environmental factors and how particular factors may influence odds of living to oldest old ages in good health. [ABSTRACT FROM AUTHOR]

Objective: 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)., 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-ε4 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 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)., Conclusion: The longevity-associated FOXO3 G -allele mitigates the impact of hypertension on the risk of CMI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Longevity is written into the genes. While many so-called "longevity genes" have been identified, the reason why particular genetic variants are associated with longer lifespan has proven to be elusive. The aim of the present study was to test the hypothesis that the strongest of 3 adjacent longevity-associated single nucleotide polymorphisms - rs3794396 - of the vascular endothelial growth factor receptor 1 gene, FLT1 , may confer greater lifespan by protecting against mortality risk from one or more adverse medical conditions of aging - namely, hypertension, coronary heart disease (CHD), stroke, and diabetes. In a prospective population-based longitudinal study we followed 3,471 American men of Japanese ancestry living on Oahu, Hawaii, from 1965 until death or to the end of December 2019 by which time 99% had died. Cox proportional hazards models were used to assess the association of FLT1 genotype with longevity for 4 genetic models and the medical conditions. We found that, in major allele recessive and heterozygote disadvantage models, genotype GG ameliorated the risk of mortality posed by hypertension, but not that posed by having CHD, stroke or diabetes. Normotensive subjects lived longest and there was no significant effect of FLT1 genotype on their lifespan. In conclusion, the longevity-associated genotype of FLT1 may confer increased lifespan by protecting against mortality risk posed by hypertension. We suggest that FLT1 expression in individuals with longevity genotype boosts vascular endothelial resilience mechanisms to counteract hypertension-related stress in vital organs and tissues.

The single nucleotide polymorphism (SNP) rs4130113 of the growth hormone receptor gene ( GHR ) is associated with longevity. Here we explored whether longevity-associated genotypes protect against mortality in all individuals, or only in individuals with aging-related diseases. Rs4130113 genotypes were tested for association with mortality in 3,557 elderly American men of Japanese ancestry. At baseline (1991-1993), 1,000 had diabetes, 730 had coronary heart disease (CHD), 1,901 had hypertension, 485 had cancer, and 919 lacked these diseases. The men were followed from baseline until Dec 31, 2019 or death (mean 10.8 ± 6.5 SD years, range 0.01-28.8 years; 99.0% deceased by that date). In a heterozygote disadvantage model, longevity-associated genotypes were associated with significantly lower mortality risk in individuals having hypertension (covariate-adjusted hazard ratio [HR] 0.83 [95% CI: 0.76-0.93, p = 4.3 x10 -4 ]. But in individuals with diabetes, CHD, and cancer there was no genotypic difference in lifespan. As expected, normotensive men outlived men with hypertension ( p = 0.036). There was no effect, however, of genotypic difference on lifespan in normotensive men ( p = 0.11). We found that SNP rs4130113 potentially influenced the binding of transcription factors E2A, MYF, NRSF, TAL1, and TCF12 so as to alter GHR expression. We propose that in individuals with hypertension, longevity-associated genetic variation in GHR enhances cell resilience mechanisms to help protect against cellular stress caused by hypertension. As a result, hypertension-affected men who possess the longevity-associated genetic variant of GHR live as long as normotensive men.

Genetic variants of the kinase signaling gene MAP3K5 are associated with longevity. Here we explore whether the longevity-association involves protection against mortality in all individuals, or only in individuals with aging-related diseases. We tested the strongest longevity associated single nucleotide polymorphism (SNP), rs2076260, for association with mortality in 3,516 elderly American men of Japanese ancestry. At baseline (1991-1993), 2,461 had either diabetes (n=990), coronary heart disease (CHD; n=724), or hypertension (n=1,877), and 1,055 lacked any of these cardiometabolic diseases (CMDs). The men were followed from baseline until Dec 31, 2019. Longevity-associated genotype CC in a major allele homozygote model, and CC + TT in a heterozygote disadvantage model were associated with longer lifespan in individuals having a CMD (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12-1.35, p= 2.5x10 -5 ] in major allele homozygote model, and 1.22 [95% CI: 1.11-1.33, p= 1.10x10 -5 ] in heterozygote disadvantage model). For diabetes, hypertension and CHD, HR p -values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. As expected, men without a CMD outlived men with a CMD ( p =1.9x10 -6 ). There was, however, no difference in lifespan by genotype in men without a CMD ( p =0.21 and 0.86, respectively, in each genetic model). In conclusion, we propose that in individuals with a cardiometabolic disease, longevity-associated genetic variation in MAP3K5 enhances resilience mechanisms in cells and tissues to help protect against cardiometabolic stress caused by CMDs. As a result, men with CMD having longevity genotype live as long as all men without a CMD.

FOXO3 is a prominent longevity gene. To date, no-one has examined whether longevity-associated FOXO3 genetic variants protect against mortality in all individuals, or only in those with aging-related diseases. We therefore tested longevity-associated FOXO3 single nucleotide polymorphisms in a haplotype block for association with mortality in 3,584 elderly American men of Japanese ancestry, 2,512 with and 1,072 without a cardiometabolic disease (CMD). At baseline (1991-1993), 1,010 CMD subjects had diabetes, 1,919 had hypertension, and 738 had coronary heart disease (CHD). Follow-up until Dec 31, 2019 found that in CMD-affected individuals, longevity-associated alleles of FOXO3 were associated with significantly longer lifespan: haplotype hazard ratio 0.81 (95% CI 0.72-0.91; diabetes 0.77, hypertension 0.82, CHD 0.83). Overall, men with a CMD had higher mortality than men without a CMD ( P =6x10 -7 ). However, those men with a CMD who had the FOXO3 longevity genotype had similar survival as men without a CMD. In men without a CMD there was no association of longevity-associated alleles of FOXO3 with lifespan. Our study provides novel insights into the basis for the long-established role of FOXO3 as a longevity gene. We suggest that the FOXO3 longevity genotype increases lifespan only in at-risk individuals by protection against cardiometabolic stress.

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries., Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys., Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries., Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: To determine the relation between height, FOXO3 genotype and age of death in humans., Methods: Observational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. A Cox regression model with age as the time scale, stratified by year of birth, was used to estimate the effect of baseline height on mortality during follow-up. An analysis of height and longevity-associated variants of the key regulatory gene in the insulin/IGF-1 signaling (IIS) pathway, FOXO3, was performed in a HHP-HAAS subpopulation. A study of fasting insulin level and height was conducted in another HHP-HAAS subpopulation., Results: A positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003-1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002-1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10-0.42; P = 0.001)., Conclusion: Height in mid-life is positively associated with mortality, with shorter stature predicting longer lifespan. Height was, moreover, associated with fasting insulin level and the longevity genotype of FOXO3, consistent with a mechanistic role for the IIS pathway.

Background: Both indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups. This study aims to examine the associations of indices of obesity in Japanese Americans (JA), African Americans (AA) and Koreans with lipoprotein subfractions., Methods: A population-based sample of 230 JA, 91 AA, and 291 Korean men aged 40-49 was examined for indices of obesity, i.e., visceral and subcutaneous adipose tissue (VAT and SAT, respectively), waist circumference (WC), and body-mass index (BMI), and for lipoprotein subfractions by nuclear-magnetic-resonance spectroscopy. Multiple regression analyses were performed in each of the three ethnic groups to examine the associations of each index of obesity with lipoprotein., Results: VAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all three ethnicities (p < 0.01). SAT, WC, and BMI had significant positive associations with total and small LDL in only JA and Koreans, while these indices had significant inverse associations with large HDL in all ethnic groups (p < 0.01). Compared to SAT, VAT had larger R 2 values in the associations with total and small LDL and large HDL in all three ethnic groups., Conclusions: VAT is significantly associated with total and small LDL and large HDL in all three ethnic groups. The associations of SAT, WC, and BMI with lipoprotein subfractions are weaker compared to VAT in all three ethnic groups.

Objective. Despite considerable study, the relevance of leptin and adiponectin for atherosclerosis development is still unsettled. We investigated relations of serum leptin and adiponectin to serum C-reactive protein (CRP), using the INTERLIPID dataset on Japanese emigrants living in Hawaii and Japanese in Japan. Design and Methods. Serum leptin, adiponectin, and CRP were measured by standardized methods in men and women of ages 40 to 59 years from two population samples, one Japanese-American in Hawaii (83 men, 89 women) and the other Japanese in central Japan (111 men, 104 women). Participants with CRP >10 mg/L were excluded. Results. Sex-specific multiple linear regression analyses, with log-transformed leptin and adiponectin (log-leptin, log-adipo), site (Hawaii = 1, Japan = 0), SBP, HbA1c, smoking (cigarettes/day), and physical activity index score of the Framingham Offspring Study as covariates, showed that log-leptin directly related and log-adipo inversely related to log-CRP for both sexes (Ps < 0.05 to <0.01). Addition to the model of BMI and interaction terms (BMI × log-leptin, BMI × log-adipo, SITE × log-leptin, SITE × log-adipo) resulted in disappearance of statistical significance except for direct relation of log-leptin to log-CRP in men (P = 0.006). Conclusions. Leptin directly related to CRP independent of BMI and other confounding factors in men but not in women.

This article provides a comprehensive review of the outcomes of polypharmacy in nursing homes. Our review had some limitations. First, we only included studies beginning in 1990, and significant earlier studies are not included. Only English language articles were included. We only researched studies from MEDLINE, and may have missed studies based on our search terms and search tools. There are many definitions of polypharmacy in the literature, including number of medications or inappropriate medications. In this review, we defined polypharmacy as a high number of medications, but not inappropriate medications. It was not surprising that polypharmacy was consistently associated with an increased number of potentially inappropriate drugs. The majority of studies were viewed showed that polypharmacy was associated with increased ADEs, increased DDIs, and increased hospitalizations. We were surprised that polypharmacy was not consistently linked with falls, fractures, and mortality. For the mortality studies, it has been postulated that perhaps some patients receiving 10 or more medications may have been moribund or receiving end-of-life or hospice care. It is possible that the number of medications is not as important as the number of potentially in appropriate drugs. There need to be more studies on these outcomes, using different definitions of polypharmacy. Polypharmacy was associated with increased costs. The drug-related morbidity and mortality, including those resulting from inappropriate medications and increased staff time, led to increased costs. Use of consultant pharmacists has been shown to decrease polypharmacy costs.

The prevalence of polypharmacy is very high in the nursing home setting. In this comprehensive review, we describe the many demographic, functional status, chronic disease, and healthcare financing factors associated with polypharmacy in nursing home patients. Recognition of the factors associated with polypharmacy is the first step for practitioners. A quality improvement intervention study previously conducted by the authors of this paper demonstrated that polypharmacy can be reduced in the nursing setting as a result of systematic review of medications by physicians.

Background: High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP)., Methods: Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD442G and Int 14A)., Results: HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p =.002) but not related to non-CVD (p =.147) or total (p =.547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Int 14A variant. These men also had higher HDL-C levels (p =.047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p =.005)., Conclusions: Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging.

Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations.

Context: The apolipoprotein E epsilon4 (APOE epsilon4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined., Objective: To examine the independent and combined effects of depression and APOE epsilon4 on the risk of dementia and its subtypes., Design: The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men., Settings and Participants: Depressive symptoms and presence of the APOE epsilon4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow-up based on neurologic assessment at 2 repeated examinations (April 1994-April 1996 and October 1997-February 1999)., Main Outcome Measures: Overall dementia, Alzheimer disease, and vascular dementia., Results: The interaction of depression and APOE epsilon4 was statistically significant in the analytical models. Compared with men with neither APOE epsilon4 nor depression, the risk of dementia in nondepressed men with APOE epsilon4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6-1.8); however, depressed men without APOE epsilon4 had a 1.6-fold greater risk (95% CI, 0.8-3.0), whereas depressed men with APOE epsilon4 had a 7.1-fold greater risk (95% CI, 3.0-16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease., Conclusions: The APOE epsilon4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE epsilon4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE epsilon4 allele. Because this cohort includes only men, further investigation in women is required.

Background: Although evidence is accumulating for a protective effect of late life physical activity on the risk of dementia, the findings are inconsistent, especially in men. We examined the association of late life physical activity and the modifying effect of physical function with future risk of dementia in a well-characterized cohort of elderly men participating in the Honolulu-Asia Aging Study (HAAS)., Methods: Physical activity by self-report and performance-based physical function was assessed in 2263 men aged 71-92 years without dementia at the baseline examination of the HAAS in 1991-1993. Follow-up for incident dementia occurred at repeat examinations conducted in 1994-1996 and 1997-1999. Analyses were based on Cox proportional hazards models with adjustment for potential confounders, including age, baseline cognitive function, education, and apolipoprotein E genotype., Results: There were 173 incident cases of dementia with a mean follow-up of 6.1 years. Although the incidence of dementia tended to decline with increasing physical activity and function, there was a significant interaction between the latter two factors on dementia risk (p =.022). For men with low physical function, high levels of physical activity were associated with half the risk of dementia versus men who were the least active (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.28-0.89), with a moderate level of physical activity also providing a protective effect (HR, 0.57; 95% CI, 0.32-0.99). Risk of dementia and Alzheimer's disease declined significantly with increasing physical activity. Findings persisted after age and risk factor adjustment. Similar associations were absent in men with moderate and high physical function., Conclusions: In elderly men with poor physical function, increasing general physical activity may potentially confer a protective effect or delay the onset for dementia.

Background: Measurement of the ankle-to-brachial index (ABI) is a noninvasive test to assess peripheral arterial disease. A low ABI is a strong correlate of cardiovascular disease and subsequent mortality. Evidence indicates the existence of vascular components in the pathogenesis of dementia. Here, we examine the association of ABI with dementia and subtypes., Methods and Results: Data are from the Honolulu-Asia Aging Study (HAAS), a prospective community-based study of 3734 Japanese American men 71 to 93 years of age at baseline in 1991 to 1993. The analysis included 2588 men who were free of dementia at the first assessment, had an ABI measure, and were examined up to 2 more times for dementia between 1994 and 1999. The sample included 240 incident cases of dementia (144 of Alzheimer's disease, 46 of vascular dementia, and 50 of dementia of other causes). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from Cox proportional-hazards models with age as the time scale after adjustment for education, year of birth, high blood pressure, body mass index, diabetes mellitus, cholesterol concentration, smoking status, alcohol consumption, and apolipoprotein E epsilon4 allele. A low ABI was associated with an increased risk of dementia and vascular dementia (HR, 1.66; 95% CI, 1.16 to 2.37; and HR, 2.25; 95% CI, 1.07 to 4.73, respectively). ABI was weakly associated with Alzheimer's disease (HR, 1.57; 95% CI, 0.98 to 2.53), particularly in the apolipoprotein E epsilon4 carriers (HR, 1.43; 95% CI, 1.02 to 1.96)., Conclusions: These results suggest that ABI, a measure of atherosclerosis, is associated with the incidence of total dementia, vascular dementia, and Alzheimer's disease in carriers of the apolipoprotein E epsilon4 allele.

The objective of this study is to investigate the relationship between lowlevels of human serum albumin (HSA) and the incidence of coronary heart disease (CHD) in a cohort of elderly Japanese-American men. Using data from the Honolulu Heart Program's fourth examination (1991-1993), HSA levels of 998 Japanese American men aged 71-93 years was compared with plasma levels of fibrinogen, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, diastolic BP, BMI, and fasting blood glucose. HSA was significantly negatively associated with age and fibrinogen, and significantly positively associated with total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, diastolic BP, BMI and fasting blood glucose. After adjusting for age, tertiles of HSA were significantly positively associated with total cholesterol, HDL cholesterol and triglycerides, and significantly negatively associated with fibrinogen. Using multivariate stepwise regression, significant correlations were seen between HSA and fibrinogen, cholesterol, age, HDL cholesterol and triglycerides, and a borderline correlation was seen with systolic blood pressure. However, the model R-square for all variables was only 0.10. In conclusion, HSA levels are significantly associated with several traditional cardiovascular risk factors, particularly serum lipid levels.

Objective: The objective of this study was to examine the relation of physical performance measures with depressive symptoms in older men., Method: A cross-sectional, multivariate comparison of several measures of upper- and lower-extremity performance and their relation with depressive symptoms was performed in 2,856 older Japanese American men, aged 71-93 years, who participated in the fourth examination of the Honolulu Heart Program. Depressive symptoms were measured using an 11-item version of Center for Epidemiologic Studies Depression (CES-D) Scale. A score of at least 9 (from a maximum score of 33) is considered clinically significant. Timed functional performance tests, including walking and repeated chair stands, were used to assess lower-extremity performance; handgrip strength was used as an indicator of upper-extremity performance., Results: Two hundred eighty-three participants (9.9%) had a score of 9 or greater on the 11-question CES-D Scale and were considered to be at high risk for depression. Time to walk 10 feet and time to complete five chair stands were significantly longer in those with depressive symptoms, whereas handgrip strength was significantly lower. Only the association of gait speed (time to walk 10 feet) and depressive symptoms remained significant when all physical performance measures were simultaneously included in a multivariate analysis., Conclusion: These results demonstrate physical performance measures, particularly gait speed, may be important potential correlates of depression in community-dwelling older men.