Calcium and vitamin D are thought to play important roles in neuronal functioning. Studies have found associations between low serum vitamin D levels and reduced cognitive functioning, as well as high serum calcium levels and reduced cognitive functioning.
To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women.
Post-hoc analysis of a randomized double-blinded placebo-controlled trial.
40 Women’s Health Initiative clinical centers across the U.S.
4143 women aged 65 years and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D trial and the Women’s Health Initiative Memory Study.
2034 women were randomized to 1000 mg of calcium carbonate combined with 400 IU of vitamin D3; 2109 women were randomized to placebo.
Primary: classifications of probable dementia or mild cognitive impairment via a 4-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests.
Mean age of participants was 71 years. During mean follow-up of 7.8 years, there were 39 cases of incident dementia among calcium plus vitamin D subjects compared to 37 cases among placebo subjects (hazard ratio=1.11, 95% CI: 0.71–1.74, p=0.64). Likewise, there were 98 cases of incident mild cognitive impairment among calcium plus vitamin D subjects compared to 108 cases among placebo subjects (hazard ratio=0.95, 95% CI: 0.72–1.25, p=0.72). There were no significant differences in incident dementia or mild cognitive impairment, or in global or domain-specific cognitive function between groups.
There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men and in other age and ethnic groups, and with other doses.
Vitamin D; Calcium; Dementia; Cognition; Mild Cognitive Impairment
Physical activity (PA) is complex and a difficult behavior to assess as there is no ideal assessment tool(s) that can capture all contexts of PA. Therefore, it is important to understand how different assessment tools rank individuals. We examined the extent to which self-report and direct assessment PA tools yielded the same ranking of PA levels.
PA levels were measured by the Modifiable Activity Questionnaire (MAQ) and pedometer at baseline among 855 white (W), African-American (AA), Japanese-American (JA), and Korean (K) men (mean age 45.3 years) in 3 geographic locations in the ERA JUMP study.
Korean men were more active than W, AA, and JA men, according to both the MAQ and pedometer (MAQ total PA [mean ± SD]: 41.6 ± 17.8, 20.9 ± 9.9, 20.0 ± 9.1, and 29.4 ± 10.3 metabolic equivalent [MET] hours/week, respectively; pedometer: 9584.4 ± 449.4, 8363.8 ± 368.6, 8930.3 ± 285.6, 8335.7 ± 368.6 steps/day, respectively). Higher levels of total PA in Korean men, as shown by MAQ, were due to higher occupational PA. Spearman correlations between PA levels reported on the MAQ and pedometer indicated positive associations ranging from rho = 0.29 to 0.42 for total activity, rho = 0.13 to 0.35 for leisure activity, and rho = 0.10 to 0.26 for occupational activity.
The 2 assessment methods correlated and were complementary rather than interchangeable. The MAQ revealed why Korean men were more active. In some subpopulations it may be necessary to assess PA domains other than leisure and to use more than 1 assessment tool to obtain a more representative picture of PA levels.
ethnic groups; exercise; pedometry; self-report; occupational activity
Polypharmacy; Long-term care; Nursing homes
FOXO3 is generally recognized as a “master” gene in aging since its association with longevity has been replicated in multiple organisms and human populations. A group of single nucleotide polymorphisms in linkage disequilibrium with a coding region has been associated with human longevity, but the actual functional variant is unidentified. Therefore, we sequenced the coding region in our long-lived Japanese American population in order to enhance resources for fine mapping this region. We demonstrate that of 38 published variants, 6 are misalignments with homologous nonallelic sequences from FOXO3B (ZNF286B), a pseudogene on a different chromosome; 2 are attributable to ZNF286B only, and the remaining 30 were unconfirmed, indicating that they are very rare and not likely involved in longevity. Furthermore, we identified a novel, unique, nonsynonymous coding variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic groups but appeared too rare for major longevity effects in our study populations.
Aging; FOXO3; Genetic; Human longevity
Although organochlorines have been reported more frequently in Parkinson’s disease (PD) brains than controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during mid-life, represent a population well suited to determine the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS.
Study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites.
With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found to be present in at least one brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. Prevalence of Lewy pathology was 75% (6/8) among brains with any 2 of the 3 compounds, 48.8% (79/162) among those with 1, and 32.7% (18/55) for those with neither (P=0.007 test for trend). While findings persisted after removing cases with PD and dementia with Lewy bodies, and when adjustments were made for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (p=0.013), results were insignificant when correcting for multiple testing.
While consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study.
Parkinson’s disease; epidemiology; Lewy body; organochlorines; pesticides
Nursing home residents are at high risk of vitamin D deficiency. There has been only one previous study about vitamin D status on admission to the nursing home, and limited data are available about associations with functional disability and chronic diseases.
Data were collected by retrospective chart review of electronic medical records and Minimum Data Set (MDS) for all veterans admitted to a VA nursing home in Honolulu, Hawai‘i, between January 2011 and June 2012. All veterans had a comprehensive geriatric assessment and measurement of serum 25-hydroxyvitamin D level within 7 days of admission. Females, hospice patients, vitamin D supplement users, and those transferred from other nursing homes were excluded, leaving a final analytic sample of 104 patients. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D level <20 ng/mL. Baseline data collected included age, ethnicity, BMI, functional disability (mobility, bathing, dressing, toileting, continence, and feeding) and prevalent chronic diseases to study cross-sectional associations of vitamin D deficiency using logistic regression.
Prevalence of vitamin D deficiency on admission to the nursing home was 49.0% (51/104) among male veterans not taking supplements. The mean age was 70.6 years (range 35–95), with ethnicity as follows: 51 (49.0%) White, 34 (32.7%) Asian, and 6 (5.8%) Black. In multiple logistic regression models adjusted for age, ethnicity and BMI, vitamin D deficiency was significantly associated with number of ADL disabilities (OR = 1.36 for each increase in ADL disability, 95%CI = 1.03–1.78, P = .03) and prevalent diabetes (OR = 2.99, 95%CI = 1.12–7.99, P = .03). When all six ADL disabilities were entered separately into the multivariate logistic regression model instead of total number of ADL disabilities, only the disability in feeding (OR = 4.74, 95%CI = 0.97–23.23, P = .05) and prevalent diabetes (OR = 2.92, 95%CI = 1.03–8.24, P = .04) remained significant. There were no significant associations between vitamin D deficiency and prevalent hypertension, hypercholesterolemia, coronary artery disease, stroke, cancer, depression or dementia.
Almost half the male patients entering a nursing home in Hawai‘i had vitamin D deficiency. A high number of ADL disabilities, disability in feeding, and prevalent diabetes were independently associated with vitamin D deficiency. Future studies should focus on targeting these patients for screening and intervention with supplementation to possibly prevent adverse health outcomes of vitamin D deficiency.
Unnecessary percutaneous endoscopic gastrostomy (PEG) tube feeding in nursing homes (NH) is a growing concern and an important area of research. Hawaii has one of the highest rates of PEG tube feeding in NH patients in the US, yet has lower rates than many NHs in Asian countries. We examined prevalence and factors associated with PEG tube feeding in NH patients in Hawaii.
We conducted an observational cohort study of all patients admitted between 2003 and 2006 to an urban 180-bed hospital-affiliated NH in Honolulu, Hawaii. Data were collected from time of admission until discharge or death through 6/30/2011, from electronic and paper medical records and Minimum Data Set (MDS). Data included demographic characteristics, baseline medical conditions, functional status, cognitive status and code status. We created a Charlson Comorbidity Index (CCI) score based on baseline medical conditions on admission, and a disability score (ADL score) and Cognitive Performance Score (CPS) using baseline MDS data. Multivariable logistic regression was used to analyze factors associated with PEG tube feeding.
Of 238 NH patients aged 45–104 years (mean 83 years), 35 (14.7%) had PEG tube feeding. Of the NH cohort, 130 (54.6%) were female, 218 (92.3%) were Asian, 123 (51.9%) had a prior stroke and 163 (72%) had dementia based on CPS score. Among the 35 PEG tube fed patients, 23 (66%) had PEG placement prior to NH admission, 12 (34%) had PEG placement after NH admission, and 26 (74%) patients had PEG tube feeding until death or the end of follow-up (61 days to 8.4 years, mean 2.4 years). Prior stroke was associated with increased likelihood of PEG tube feeding (aOR = 2.52, 95%CI = 1.03–6.17, P = .04); with borderline increased likelihood for high comorbidity index (aOR = 2.21, 95%CI = 0.89–5.52, P = .09) and high ADL disability score (aOR = 2.03, 95%CI = 0.87–4.73, P = .10). DNR status was inversely associated with PEG tube feeding (aOR = 0.31, 95%CI = 0.11–0.85, P = .02). Age, dementia, Medicaid status, previous speech or physical therapy, and weight loss were not significantly associated with PEG tube feeding.
In this predominantly Asian-American NH cohort with high prevalence of PEG tube feeding, prior stroke was strongly associated with PEG tube feeding, while dementia was not. Further study is needed to examine ways to identify and reduce unnecessary tube feeding in this population.
Hospital readmissions within 30 days are increasingly targeted as a quality parameter. Frail nursing home patients are at high risk for hospitalization. The purpose of this study was to examine baseline prevalent chronic diseases associated with hospital readmission within 30 days.
We collected data on demographics and prevalent diseases for all patients admitted to one hospital-affiliated nursing home between January 2003 and December 2006, with follow-up data on pneumonia episodes and hospitalizations through June 2011. Multivariable logistic regression models identified baseline prevalent chronic diseases associated with hospital readmission within 30 days of nursing home admission.
Of 238 patients (mean age 83.4, range 45-103) admitted to the nursing home, 156 (65.5%) originally came from hospitals, 54.6% were female, 92.4% were Asian, 43.6% were on Medicaid, and 76.5% were first admitted for intermediate care and 23.5% for skilled nursing care. Although recent pneumonia was the factor most strongly associated with hospital readmission (OR = 14.5, P <.0001), in the model without pneumonia, chronic diseases associated with 30-day hospital readmission included pulmonary disease (OR = 2.2, 95%CI = 1.1–4.3, P = .019) and congestive heart failure (OR = 1.8, 95%CI = 1.0–3.4, P = .055). There were no significant associations between hospital readmission and myocardial infarction, stroke, cancer, diabetes, and dementia.
Among nursing home patients, although recent pneumonia was the strongest risk factor for 30-day hospital readmission, those with baseline chronic pulmonary disease and congestive heart failure were at especially high risk for hospital readmission within 30 days of nursing home admission. These patients may benefit from care focused on preventing hospital readmissions.
Background and Purpose
Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease, especially stroke. We examined the relationship between dietary vitamin D intake and 34-year incident stroke.
The Honolulu Heart Program is a prospective population-based cohort study of 8,006 Japanese-American men in Hawaii who were 45-68 years old at the baseline examination in 1965-68. Dietary vitamin D intake was calculated using the Nutritionist IV v3 software from a 24-hour dietary recall. Subjects with prevalent stroke were excluded, leaving 7,385 men followed through 1999 for incident stroke. Subjects were divided into quartiles of dietary vitamin D for analyses.
During 34 years of follow-up, 960 subjects developed stroke. Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared to the highest (all stroke: 6.38 vs. 5.14 per 1,000 person-years follow-up, p=0.030; thromboembolic stroke: 4.36 vs. 3.30, p=0.033). Using Cox regression, adjusting for age, total kilocalories, BMI, hypertension, diabetes mellitus, pack-years smoking, physical activity index, serum cholesterol, and alcohol intake, those in the lowest quartile had a significantly increased risk of incident stroke (all stroke HR=1.22, 95% CI=1.01-1.47, p=0.038; thromboembolic stroke HR=1.27, 95% CI=1.01-1.59, p=0.044), with the highest as reference. We found no significant associations between dietary vitamin D and hemorrhagic stroke.
Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men. Additional research is needed on vitamin D supplementation to prevent stroke.
dietary vitamin D intake; incident stroke; Japanese-American men; longitudinal cohort study
We recently reported that Japanese had higher liver fat at a lower level of BMI compared with non-Hispanic whites (NHW).
We hypothesize that ethnic difference in fat storage capacity contributes to this ethnic difference in liver fat.
To examine this, we assessed liver fat among 244 Japanese-American aged 40-49, using regional computed-tomography images, along with metabolic variables.
Despite the similar BMI between Japanese-Americans and NHW men, Japanese-Americans had more liver fat (liver to spleen attenuation ratio: 1.03 ± 0.22 for Japanese-Americans, and 1.07 ± 0.15 for NHW men; p<0.05) and tended to have a greater disposition for fatty liver with an increase in BMI than NHW, indicating a clear difference between the two groups. In addition, liver fat is less in Japanese-Americans compared with Japanese men (1.03 ± 0.22 vs. 1.01 ± 0.16; p<0.05), despite of a much higher BMI. These ethnic differences support the hypothesis that higher fat storage capacity indeed seems to be associated with less liver fat. In all the groups, liver fat content strongly correlated with triglycerides, homeostasis model assessment-insulin resistance, and C-reactive protein (CRP). Nevertheless, these metabolic variables were worse in Japanese-Americans, despite of less liver fat, compared with Japanese. Moreover, CRP levels were least among Japanese with highest liver fat, and highest among NHW men with least liver fat, despite of a strong positive association between CRP and fatty liver within each population.
Fat content in the liver is intermediate for Japanese-Americans compared with Japanese and NHW men, which supports the hypothesis of less fat storage capacity among Japanese, closely linked to ethnic difference in predisposition to fatty liver.
Ethnicity; Fatty liver; Genetic; Environmental; CRP
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 (≥411.0 mg/d) were less likely than men in the lowest quartile (≤137.0 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.
Caffeine; coffee; cohort studies; dementia
In the 1990’s Iceland and Japan were known as countries with high fish consumption whereas coronary heart disease (CHD) mortality in Iceland was high and that in Japan was low among developed countries. We described recent data fish consumption and CHD mortality from publicly available data. We also measured CHD risk factors and serum levels of marine-derived n-3 and other fatty acids from population-based samples of 1,324 men in Iceland, Japan, South Korea, and the US. CHD mortality in men in Iceland was almost 3 times as high as that in Japan and South Korea. Generally a profile of CHD risk factors in Icelanders compared to Japanese was more favorable. Serum marine-derived n-3 fatty acids in Iceland were significantly lower than in Japan and South Korea but significantly higher than in the US.
n-3 fatty acids; eicosapentaenoic acid; docosaehexaenoic acid; coronary heart disease; descriptive epidemiologic study
Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men.
We examined the association in 906 men aged 40–49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography.
Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1–100 (n=411), 101–300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group.
The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40’s.
aortic stiffness; aortic calcification; international multi-ethnic study
Explanations for the low prevalence of atherosclerosis in Japan versus United States are often confounded with genetic variation. To help remove such confounding, coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was compared between Japanese men in Japan and Japanese men in Hawaii. Findings are based on risk factor and CAC measurements that were made from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40 to 50 years and without cardiovascular disease. After age-adjustment, there was a 3-fold excess in the odds of prevalent CAC scores ≥10 in Hawaii versus Japan (relative odds [RO] = 3.2; 95% confidence interval [CI] = 2.1,4.9). While men in Hawaii had a generally poorer risk factor profile, men in Japan were 4-times more likely to smoke cigarettes (49.5 vs. 12.7%, p<0.001). In spite of marked risk factor differences between the samples, none of the risk factors provided an explanation for the low amounts of CAC in Japan. After risk factor adjustment, the RO of CAC scores ≥10 in Hawaii versus Japan was 4.0 (95% CI = 2.2,7.4). Further studies are needed to identify factors that offer protection against atherosclerosis in Japanese men in Japan.
Atherosclerosis; cohort studies; coronary disease; Japan; men; risk factors
Brain iron promotes neurodegeneration in Parkinson’s disease (PD). While hemoglobin (Hb) is the most abundant source of peripheral iron in humans, its relationship with PD is uncertain. This report examines the association between Hb in late-life and PD incidence.
From 1991-1993, Hb was measured in 3,507 men in the Honolulu-Asia Aging Study. Men were aged 71-93 years and without PD. Participants were followed until 2001 for incident PD.
Hb levels declined markedly with age. For men aged 71-75 years, 14.8% had levels <14 g/dL versus 53.6% in those aged 86 and older (p<0.001). During follow-up, 47 men developed PD (19.8/10,000 person-years). After age-adjustment, PD incidence rose significantly from 10.3 to 34.9/10,000 person-years as Hb increased from <14 to ≥16 g/dL (p=0.024, relative hazard 3.2, 95% CI 1.2-8.9). Associations persisted after accounting for early mortality and adjustments for concomitant risk factors.
While Hb declines with advancing age, evidence suggests that Hb that remains high in elderly men is associated with an increased risk of PD.
Hemoglobin; iron; Parkinson’s disease; epidemiology
Sociocultural factors have been implicated in affecting prevalence, incidence, and diagnosis of depression but previous studies have included heterogeneous ethnic populations. We studied the influence of cultural assimilation on the prevalence and presentation of depressive symptoms in elderly Japanese-American men.
This analysis was based on 3,139 Japanese-American men aged 71–93 years who were participants in the Honolulu-Asia Aging Study between 1991 and 1993. We created a Cultural Assimilation Scale (CAS) using 8 questions assessing the degree of Japanese identity and lifestyle compared to a Western one. Subjects were divided into tertiles of CAS score for analysis. Prevalence of depressive symptoms was measured using an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire (CESD-11), and presence of depressive symptoms was defined as score ≥ 9.
Prevalent depressive symptoms did not reach a statistically significant association with CAS tertiles (Western 10.8%, Mixed 9.6%, Japanese 8.5%). However after adjusting for demographic, functional and disease factors, the most culturally Japanese group had significantly lower odds for prevalent depressive symptoms, compared to the most Western group. Among the subset of subjects with a high CESD-11 score, there were no significant differences in both mean psychological scores and mean somatic scores between the three Cultural Assimilation Scale groups.
Prevalent depressive symptoms were significantly lower among elderly Japanese-American men who were most culturally Japanese, compared to more Westernized men. Improving knowledge and understanding about the pathogenesis of depression will have important public health implications.
Beta-amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer’s disease (AD) and possibly vascular dementia (VaD). We investigated the joint association of mid-life BP and Aβ peptide levels with the risk for late-life AD and VaD. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965 – 2000). Mid-life BP was measured starting in 1971 participants mean age 58 years, Aβ was measured in specimens collected1980/82, and assessment of dementia and autopsy collection started in 1991/93. The outcome measures were prevalent (present in 1991/3) and incident AD (n= 53, including 38 with no contributing cardiovascular disease), and VaD (n=24). Cerebral amyloid angiopathy (CAA), β-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in post-mortem tissue. The risk for AD significantly increased with lower levels of plasma Aβ (Aβ1-40 hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.4 – 3.1; Aβ1-42 HR 1.6, 95% CI 1.1 – 2.3). Evidence of interaction between diastolic BP and plasma Aβ (1-40 pinteraction <0.05; 1-42 pinteraction <0.07) levels, indicated the Aβ-related risk for AD was higher when BP was higher. Low plasma Aβ was associated with the presence of CAA (ptrend<0.05), but not the other neuropathologies. Aβ plasma levels start decreasing at least 15 years before AD is diagnosed, and the association of Aβ to AD is modulated by mid-life diastolic BP. Elevated BP may compromise vascular integrity leading to CAA and impaired Aβ clearance from the brain.
Amyloid; blood pressure; brain; aging; dementia
Sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disorder of unknown etiology that causes rapidly progressive dementia. This disease is uniformly fatal and most patients die within 12 months. Clinical findings include myoclonus, visual disturbances, and cerebellar and pyramidal/extrapyramidal signs in addition to rapidly progressive cognitive and functional impairment. These findings are all non-specific and it is often difficult and challenging to diagnose premortem because of low awareness and clinical suspicion.
We present a 66-year-old woman with a 5-month history of rapidly progressive dementia. After a series of extensive diagnostic examinations and continuous follow-up, she was diagnosed with probable sporadic Creutzfeldt-Jakob disease based on Centers for Disease Control and Prevention (CDC) criteria, with key findings of rapidly progressive dementia, blurry vision, extrapyramidal signs (cogwheel rigidity), and abnormal hyperintensity signals on diffusion-weighted MRI. Her symptoms progressively worsened and she died 7 months after the onset. The postmortem brain autopsy demonstrated the presence of abnormal protease-resistant prion protein by Western Blot analysis.
A literature review was performed on differential diagnoses that present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease. These include Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, meningoencephalitis, corticobasal degeneration, progressive supranuclear palsy, CADASIL, and paraneoplastic encephalomyelitis.
sporadic Creutzfeldt-Jakob disease; prion disease; rapidly progressing dementia
The objective of this study was to identify risk factors ascertained at baseline that were associated with prevalence and incidence of fractures at advanced age among Japanese-American men.
The present study used data from Honolulu Heart Program (HHP) and Honolulu-Asia Aging Study (HAAS). The HHP was a prospective study with primary focus on risk factors for cardiovascular diseases and stroke. A cohort of 8,006 men of Japanese ancestry aged 45–68 residing on Oahu was recruited in 1965, and followed through 1999. The HAAS started in 1991 in conjunction with the HHP with a focus on age-related health conditions. Self-reported cumulative prevalence of hip, spine and forearm fractures was ascertained in 1991–1993 among 3,845 men aged 71–93. Incidence was obtained during the follow-up period (1994–1999) among 2,737 men aged 74–98. Poisson regression models were used to determine multi-variable adjusted prevalence and incidence ratios for fracture.
Baseline age was directly and inversely associated with cumulative incident spine and prevalent forearm fracture, respectively. Education was inversely and directly associated with prevalent spine and forearm fracture, respectively. Body mass index (BMI) was independently and directly, and upper arm girth was inversely associated with incident hip fracture. Height and diabetic medication were directly associated with prevalent spine fracture. Physical activity and pack-years of smoking were independently and directly associated with incident and prevalent hip fracture, respectively.
These results indicated that multiple baseline demographic lifestyle and anthropometric characteristics predict fracture risk at advanced age. In addition, associations varied by fracture location.
fracture; incidence ratio; men; prevalence ratio; risk factors
Cigarette smoking is a risk factor of coronary heart disease (CHD). Vascular calcification such as coronary artery calcium (CAC) and aortic calcium (AC) is associated with CHD. We hypothesized that cigarette smoking is associated with coronary artery and aortic calcifications in Japanese and Koreans with high smoking prevalence.
Random samples from populations of 313 Japanese and 302 Korean men aged 40 to 49 were examined for calcification of the coronary artery and aorta using electron beam computed tomography. Coronary artery calcium (CAC) and aortic calcium (AC) were quantified using the Agatston score. We examined the associations of cigarette smoking with CAC and AC after adjusting for conventional risk factors and alcohol consumption. Current and past smokers were combined and categorized into two groups using median pack-years as a cutoff point in each of Japanese and Koreans. The never smoker group was used as a reference for the multiple logistic regression analyses.
The odds ratios of CAC (score ≥10) for smokers with higher pack-years were 2.9 in Japanese (P<0.05) and 1.3 in Koreans (non-significant) compared to never smokers. The odds ratios of AC (score ≥100) for smokers with higher pack-years were 10.4 in Japanese (P<0.05) and 3.6 in Koreans (P<0.05).
Cigarette smoking with higher pack-years is significantly associated with CAC and AC in Japanese men, while cigarette smoking with higher pack-years is significantly associated with AC but not significantly with CAC in Korean men.
atherosclerosis; cigarette smoking; coronary calcium; aortic calcium; Japanese; Koreans
To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia.
Case-control study nested in a prospective cohort.
The Honolulu-Asia Aging Study on Oahu, Hawaii.
3468 Japanese American men (mean age 52, 1965–1968) examined for dementia after 25 years.
Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index <25.0 kg/m2, physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruit, vegetables, cereals, and monounsaturated-to-saturated fat). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for developing overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD), adjusting for potential confounders.
Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with increased risk of overall dementia (OR, 1.87; 95% CI, 1.26–2.77; BMI >25.0 vs. <22.6 kg/m2). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of cohort) had the lowest OR for overall dementia (OR, 0.36; 95% CI, 0.15–0.84), as compared to other men. There were no significant associations between the combined low-risk characteristics and the risk of AD alone.
Having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life among Japanese American men.
dementia; lifestyle; risk
Co-heritability of hypertension and insulin resistance (IR) within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome (MetS). Thus we determined whether the T323C polymorphism (rs5333) of endothelin type A (ETA) receptor, a predominant receptor evoking potent vasoconstrictive action of endothelin-1, contributes to susceptibility to IR-associated hypertension in 1694 subjects of Chinese and Japanese origins. Blood pressures (BPs) and biochemistries were measured. Fasting insulin level, insulin-resistance homeostasis model assessment (HOMAIR) score, and area under curve of insulin concentration (AUCINS) were selected for assessing insulin sensitivity. Genotypes were obtained by methods of polymerase chain reaction-restriction fragment length polymorphism. Foremost findings were that minor allele frequency of the T323C polymorphism was noticeable lower in our overall Asian subjects compared to multi-national population reported in gene database; moreover both the genotypic and allelic frequencies of the polymorphism were significantly different between the two ethnic groups we studied. The genotype distributions at TT/TC/CC were 65, 31, 4% in Chinese and 51, 41, 8% in Japanese, respectively (p < 0.0001). Additionally, carriers of the C homozygote revealed characteristics of IR, namely significantly higher levels of fasting insulin, HOMAIR score, and AUCINS at 29.3, 35.3, and 39.3%, respectively, when compared to their counterparts with TT/TC genotypes in Chinese. Meanwhile, the CC genotype was associated with a higher level of high density lipoprotein cholesterol in Japanese. No association of the polymorphism with BP was observed. This study demonstrated for the first time that T323C polymorphism of ETA receptor gene was associated with an adverse insulin response in Chinese and a favorite atherogenic index in Japanese.
ETA receptor; T323C polymorphism; metabolic syndrome; hypertension
We examined several risk factors as possible independent predictors of aortic stiffness progression among a population based sample of US men.
Methods and Results
A total of 240 men aged 40–49 from the Allegheny County site of the ERA JUMP Study, who were free of CVD at baseline were evaluated. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) at baseline and after 4.6±0.21(mean±SD) years of follow-up. Progression of cfPWV was evaluated as relative annual change in cfPWV (% change/year). Using linear regression, both baseline potential risk factors and their annual changes were evaluated as possible risk factors for cfPWV progression. Baseline age, follow-up time, race, heart rate, and medications use were forced in all models. During follow-up, relative to baseline level, cfPWV increased 0.3%±5.3% per year. In final models the independent predictors of degree of cfPWV progression were lower levels of adiponectin (β(SE): −1.8(0.8), P=0.03), higher levels of systolic blood pressure (SBP) (β(SE): 0.07(0.03), P=0.02), greater annual change in SBP (β(SE): 0.3(0.2), P=0.04), and alcohol consumption ≥ 2 times/week (β(SE): 1.6(0.7), P=0.02).
Lower levels of adiponectin, higher levels and annual changes of SBP, and alcohol consumption ≥2 times/week are associated with greater progression in aortic stiffness among relatively healthy middle-aged US men.
arteriosclerosis; hypertension; risk factors; pulse wave velocity; stiffness
The frequency of neurocognitive impairment (NCI) in human immunodeficiency virus (HIV)-infected individuals remains high despite the availability of potent antiretroviral therapy (ART). The concurrence of depression among HIV-infected patients with NCI is common, especially among older individuals. Depression has been implicated as a risk factor for impaired neuropsychological performance (NP). This study explored the relationship between depressive symptoms and NP testing in HIV-infected individuals.
A cross-sectional analysis was performed within the Hawaii Aging with HIV Cohort, a large prospective study of cognition of older (50 or more years old) compared to younger (20 to 39 years old) HIV-infected individuals.
Two hundred and eighty-five HIV infected participants (157 older and 128 younger) were administered a battery of NP tests to measure performance in major cognitive domains. Depressive symptoms were measured using the Beck Depression Inventory (BDI). The rates of depressive symptoms and neuropsychological impairment were similar in older and younger groups. Multivariate analyses revealed depressive symptoms were associated with NP test impairment in the younger group. In the older group, depressive symptoms were not associated with NP.
This study suggests that depressive symptoms are associated with NP test impairment in younger HIV-infected individuals, but not in older individuals.
Depression; HIV; Neurocognitive Function; Aging
Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain.
In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, US, 302 Japanese in Kusatsu, Japan, and 229 Japanese Americans in Honolulu, Hawaii, US), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic, and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association.
White, Japanese, and Japanese American men had mean marine n-3 FAs levels of 3.47%, 8.78%, and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, p=0.049), after adjusting for age, body-mass index, and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese American men did not show a significant association.
We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.
fibrinogen; marine n-3 fatty acids; epidemiology; Japanese