Study Of Japanese-American Men Research Articles

Novel Functional, Health, and Genetic Determinants of Cognitive Terminal Decline: Kuakini Honolulu Heart Program/Honolulu-Asia Aging Study.

To investigate interindividual differences in cognitive terminal decline and identify determinants including functional, health, and genetic risk and protective factors, data from the Honolulu Heart Program/Honolulu-Asia Aging Study, a prospective cohort study of Japanese American men, were analyzed. The sample was recruited in 1965-1968 (ages 45-68 years). Longitudinal performance of cognitive abilities and mortality status were assessed from Exam 4 (1991-1993) through June 2014. Latent class analysis revealed 2 groups: maintainers retained relatively high levels of cognitive functioning until death and decliners demonstrated significant cognitive waning several years prior to death. Maintainers were more likely to have greater education, diagnosed coronary heart disease, and presence of the apolipoprotein E (APOE) ε2 allele and FOXO3 G allele (SNP rs2802292). Decliners were more likely to be older and have prior stroke, Parkinson's disease, dementia, and greater depressive symptoms at Exam 4, and the APOE ε4 allele. Findings support terminal decline using distance to death as the basis for modeling change. Significant differences were observed between maintainers and decliners 15 years prior to death, a finding much earlier compared to the majority of previous investigations.

Abstract P274: Association Between Atrial Fibrillation and Central Sleep Apnea in Older Japanese-American Men

Introduction: Several studies have indicated that central sleep apnea (CSA) is associated with atrial fibrillation (AF) in older populations. However, there are few studies of this association in older Asian populations. Hypothesis: The hypothesis being tested is that there is an association between AF and CSA in older Japanese-American men. Methods: The Kuakini Honolulu-Asia Aging Study is a longitudinal cohort study of Japanese-American men living in Hawaii. We did a cross- sectional analysis using data from the 1999- 2000 7th exam cycle. Participants were 718 Japanese-American men between 79 and 97 years old, who had overnight polysomnography (PSG) conducted in their homes using criteria established by the large multicenter Sleep Heart Health Study. Obstructive Apnea-Hypopnea Index (OAHI) was the measure of the number of obstructive apneas and hypopneas with >4% oxygen desaturation. Additionally, the Central Apnea Index (CAI) was the measure of the number of central apneas. Obstructive sleep apnea (OSA) was categorized as none (OAHI <5), mild (OAHI 5-14), moderate (OAHI 15-29) and severe (OAHI 30 or more). CSA was defined by CAI of 5 or more. Cheyne-Stokes Breathing (CSB) was defined as a minimum consecutive 10-minute period of a crescendo-decrescendo respiratory pattern associated with CSA. A board-certified physician confirmed AF by single lead electrocardiography of PSG. Results: The mean age of participants was 83.2±0.2 years. The prevalence of AF was 5.5% (39 of 709). The prevalence proportions of severe OSA, CSA, and CSB were 20.5% (145 of 709), 6.3% (43 of 681) and 3.2%, (22 of 681) respectively. In multivariable-adjusted logistic regression models, CSA and CSB were significantly associated with AF prevalence [Odds Ratio (OR) 4.78; 95% Confidential interval (CI), 1.91-11.95] and [OR 5.48; 95% CI, 1.70-17.66], respectively. In contrast, OSA was not significantly associated with AF prevalence (severe OSA [OR 1.17; 95% CI, 0.44-3.11], moderate OSA [OR 0.72; 95% CI, 0.26-2.05], mild OSA [OR 0.97; 95% CI, 0.39-2.44]). Conclusion: There is an association of AF prevalence with CSA and CSB in older Japanese-American Men. In older Japanese men, screening for CSA and CSB might be important to prevent AF.

Associations of brain lesions at autopsy with polysomnography features before death.

To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia. The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO₂), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals. Sleep duration with SpO₂ <95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO₂ <95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO₂ <95% (adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO₂ during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration. The findings support a role for lower nocturnal oxygenation and SWS in the development of microinfarcts and brain atrophy, but not Alzheimer lesions or LBs.

Antihypertensive medication use and risk of cognitive impairment

To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men. The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men conducted in Honolulu, Hawaii. We examined 2,197 participants (mean age 77 years at cohort entry, 1991-1993, followed through September 2010) with hypertension and without dementia or cognitive impairment at baseline, who provided information on medication use. Cognitive function was assessed at 7 standardized examinations using the Cognitive Abilities Screening Instrument (CASI). Cognitive impairment was defined as a CASI score <74. A total of 854 men developed cognitive impairment (median follow-up, 5.8 years). β-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (incidence rate ratio [IRR] 0.69; 95% confidence interval [CI] 0.50-0.94), as compared with men not taking any antihypertensive medications, adjusting for multiple potential confounders. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment. Results were similar excluding those with cardiovascular disease or <1 year of follow-up, and additionally adjusting for pulse pressure, heart rate, baseline and midlife systolic blood pressure, and midlife antihypertensive treatment (IRR 0.65; 95% CI 0.45-0.94). The association between β-blocker use and cognitive impairment was stronger among men with diabetes, men aged >75 years, and those with pulse pressure ≥70 mm Hg. β-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men.

Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study.

Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of Japanese American men born 1900-1919. Brain magnetic resonance imaging (MRI) (1.5 T) was acquired on a stratified subsample (n = 477) that included four groups defined by cognitive status relative to the scan date: subjects without dementia (n = 347), subjects identified as demented 2-3 years before brain scanning (n = 30), at the time of scanning (n = 58), and 3-5 years after scanning (n = 42). Volumes of the striatum, including the accumbens, putamen, and caudate nucleus were automatically estimated from T1 MR images. Global cognitive function was measured with the cognitive ability screening instrument (CASI), at four examinations spanning an 8-year interval. Trajectories of cognitive decline were estimated for each quartile of striatal volume using mixed models, controlling for demographic variables, measures of cerebro-vascular damage, global brain atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after brain scanning was associated with smaller volumes of n. accumbens and putamen, but not with caudate nucleus volume. Subjects in the lowest quartile of n. accumbens volume, both in the total sample and in the subjects not diagnosed with dementia during the study, had a significantly (p < 0.0001) steeper decline in cognitive performance compared with those in the highest quartile. In conclusion, volumes of the n. accumbens and putamen are closely associated with the occurrence of dementia and n. accumbens volume predicts cognitive decline in older people. These associations were found independent of the magnitude of other pivotal markers of cognitive decline, i.e. cerebro-vascular damage and hippocampal volume. The present study suggests a role for the ventral striatum in the development of clinical dementia.

Midlife C-reactive protein and risk of cognitive decline: A 31-year follow-up

There is evidence for a relationship between raised inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), measured late in life, and an increased risk of cognitive decline and dementia. This study evaluates the association of midlife hs-CRP concentrations with late-life longitudinal trends in cognitive function. Data are from the Honolulu-Asia Aging Study (HAAS), a longitudinal community-based study of Japanese American men. hs-CRP levels were measured on average 25 years before cognitive testing began in 1991. Subjects were followed from up to three follow-up examinations (mean of 6.1 years). At each exam, cognitive function was measured with the Cognitive Abilities Screening Instrument (CASI). This analysis includes a sub-sample of 691 subjects dementia-free in 1991. With incident dementia cases included, those with the highest quartile of hs-CRP had significantly more cognitive decline than those in the lowest quartile, after adjustment for baseline CASI score, demographic and cardiovascular risk factors. When cases were removed, there was no difference in cognitive decline by CRP quartile. This relationship was not modified by the presence of apolipoprotein E ɛ4. These findings suggest that inflammatory mechanisms during midlife may reflect underlying processes contributing to dementia-related cognitive decline late in life.

Midlife Pulse Pressure and Incidence of Dementia

Previous studies have shown that midlife systolic blood pressure (SBP) predicts late-life cognitive decline and incident dementia. This study explores whether this association is attributable to the pulsatile, ie, pulse pressure (PP), or the nonpulsatile component of blood pressure (BP). Data are from the Honolulu-Asia Aging Study, a community-based study of Japanese American men. Midlife BP was measured in 1971 to 1974 and dementia assessment was conducted in late-life. The 2505 men who were dementia free in 1991 and had complete follow-up data were re-examined for incident dementia in 1994 to 1996 and 1997 to 1999. Their age ranged from 71 to 93 years. Survival analysis with age as the time scale was performed to estimate the risk (hazard ratio [HR] and 95% CI) for incident dementia associated with mid- and late-life tertiles of PP and mean arterial BP, as well as SBP and diastolic BP categories. Over a mean of 5.1 years of follow-up, 189 cases (7.5%) of incident Alzheimer disease or vascular dementia were identified. After adjustment for cerebrovascular risk factors, dementia was significantly associated with SBP (HR 1.77; 95% CI, 1.10 to 2.84, for SBP > or =140 mm Hg compared with SBP <120 mm Hg), but not with PP tertiles. Limiting the analysis to those never treated with antihypertensives, high levels of all 4 BP components were significantly associated with dementia. In models with 2 BP components, only SBP remained significant in both the total sample and the never-treated subgroup (HR 2.29; 95% CI, 1.23 to 4.25, for SBP > or =140 mm Hg in total sample), whereas PP was not significantly associated with the risk for dementia. Midlife PP is not independently associated with dementia incidence. Midlife SBP is the strongest BP component predicting incident dementia.

A 32-Year Prospective Study of Change in Body Weight and Incident Dementia

The course of weight loss associated with dementia is unclear, particularly prior to and around the onset of the clinical syndrome. To compare the natural history of weight change from mid to late life in men with and without dementia in late life. The Honolulu-Asia Aging Study, a 32-year, prospective, population-based study of Japanese American men who had been weighed on 6 occasions between 1965 and 1999 and who had been screened for dementia 3 times between 1991 and 1999. Of 1890 men (aged 77-98 years), 112 with incident dementia were compared with 1778 without dementia at the sixth examination (1997-1999). Weight change up to and including the sixth examination was treated as the dependent variable and estimated using a repeated measures analysis. Groups with and without dementia did not differ with respect to baseline weight or change in weight from mid to late life (first 26 years' follow-up). In the late-life examinations (final 6 years), mean age- and education-adjusted weight loss was -0.22 kg/y (95% confidence intervals, -0.26 to -0.18) in participants without dementia. Men with incident dementia at the same examination had an additional yearly weight loss of -0.36 kg (95% confidence interval, -0.53 to -0.19). This was not changed substantially with adjustment for risk factors for vascular disease or functional impairment and was significant for both Alzheimer disease and vascular dementia subtypes. Dementia-associated weight loss begins before the onset of the clinical syndrome and accelerates by the time of diagnosis. The potential impact on prognosis should be considered in the case of elderly persons at risk for dementia.

Is cholesterol a risk factor for stroke?: Yes.

A THEROSCLEROSIS is the most common cause of coronary artery disease (CAD), peripheral vascular disease, and stroke worldwide. Atherogenesis is a multifactorial process involving cholesterol internalization, vascular smooth muscle cell proliferation, inflammation, “foam cell” formation, and connective tissue production. Experimental and epidemiological studies of CAD, peripheral vascular disease, and stroke have identified powerful risk factors that directly affect these multifactorial processes and include hypertension, diabetes, smoking, and aging. The relevance of cholesterol, however, has only been definitively associated with CAD and peripheral vascular disease, and has a seemingly tentative and controversial role with strokes. For example, in the Framingham Study no correlation was found between cholesterol and vascular disease of the brain. The Honolulu Heart Study of Japanese American men showed no significant association with cerebral infarction but an inverse relationship with intracerebral hemorrhage. However, in the large Multiple Risk Factor Intervention Trial of more than 350 000 men, death from nonhemorrhagic strokes correlated with elevated cholesterol, suggesting but not proving an association with atherothrombotic brain infarction (ABI). The Eastern Stroke and Coronary Heart Disease Collaborative Research Group study of 69 767 participants revealed a trend toward a reduction in the risk of nonhemorrhagic stroke with decreasing cholesterol concentrations. How can this apparent paradox be explained and resolved when it is recognized that the arterial tree throughout the body is continuous, and the expectation is that risk factors for atherosclerosis for one area, such as the coronary circulation, might be the same as another, such as the cerebral circulation? A possible explanation may be that the cerebral vasculature has inherent biological processes that differ from other vascular beds with respect to endothelial cell function and does not experience the same degree of mechanical trauma exerted on the heart or other peripheral vessels that augment shear and stress forces that provoke and aggravate atherogenesis. In addition, previous studies have technical limitations in their analyses of cholesterol fractionation and of stroke subtypes, particularly distinguishing strokes due to atherosclerosis from other causes. However, while these inaccuracies may help to clarify the presumed paradox, the multifactorial process of atherogenesis cannot be reduced to these factors alone. For example, genetic, racial, environmental, and other as yet to be proven factors, such as hyperhomocysteinemia, are recognized to play a role. Nonetheless, laboratory evidence supports the major role of cholesterol trafficking in the molecular biology of atherothrombotic brain infarction (ABI). For example, patients with ABI have demonstrated abnormal dynamic synthesis and turnover for highdensity lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C) compared with healthy individuals and longitudinal follow-up results of subjects with carotid stenoses show plasma LDL-C levels to strongly predict stenosis progression. Despite these mounting evidences implicating an association of cholesterol in ABIs, they have eluded appreciation. A methodological problem with stroke diagnosis is the fact that “stroke” is not a diagnosis of a single pathological entity but rather a generic term for a variety of cerebrovascular disorders. These include subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction. And the last may be due to ABI, or a variety of other arterial diseases, emboli from heart or aorta, and prothrombotic states. Only definitive cases of ABI should be correlated with cholesterol levels, but, unfortunately, other stroke subtypes have often been included in analyses of cholesterol in “strokes.” Thus, the inclusion of patients with cardioembolic stroke due to atrial fibrillation or lacunar stroke due to hypertension or diabetes dilutes the stroke group with stroke due to atherosclerosis. Of course, the only reliable way to differentiate these stroke subtypes is by precise neuroimaging and/or autopsy information, which were less commonly performed or available when most studies had been done during the 1960s and 1970s. Unfortunately, death certificate information, without autopsy study, is often used, yet both are particularly unreliable, especially between counFrom the Departments of Neurology, University of Texas–Houston Medical School, Houston (Drs Demchuk and Yatsu), Medical College of Georgia and Veterans Affairs Medical Center, Augusta, Ga (Dr Hess), and Yale University School of Medicine, and Veterans Affairs Medical Center, New Haven, Conn (Dr Brass). CONTROVERSIES IN NEUROLOGY