12-OH-17,18-Epoxyeicosatetraenoic acid alleviates eosinophilic airway inflammation in murine lungs.

BACKGROUND: Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs. METHODS: Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies. RESULTS: Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4. CONCLUSION: These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma.

Marinesco bodies and substantia nigra neuron density in Parkinson's disease.

AIM: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal ageing and is high in Alzheimer's disease, dementia with Lewy bodies and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons. Whether MB have a role in this process is unknown. Our aim is to examine the association of MB with SN neuron density in Parkinson's disease (PD) in the Honolulu-Asia Aging Study. METHODS: Data on MB and neuron density were measured in SN transverse sections in 131 autopsied men aged 73-99 years at the time of death from 1992 to 2007. RESULTS: Marinesco body frequency was low in the presence vs. absence of PD (2.3% vs. 6.6%, P < 0.001). After PD onset, MB frequency declined as duration of PD increased (P = 0.006). Similar patterns were observed for SN neuron density. When MB frequency was low, neuron density was noticeably reduced in the SN ventrolateral quadrant, the region most vulnerable to PD neurodegeneration. Low MB frequency was unique to PD as its high frequency in non-PD cases was unrelated to parkinsonian signs and incidental Lewy bodies. Frequency was high in the presence of Alzheimer's disease and apolipoprotein ε4 alleles. CONCLUSIONS: While findings confirm that MB frequency is low in PD, declines in MB frequency continue with PD duration. The extent to which MB have a distinct relationship with PD warrants clarification. Further studies of MB could be important in understanding PD processes.

Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

Methodological review: measured and reported congruence between preferred and actual place of death.

Congruence between preferred and actual place of death is an important palliative care outcome reported in the literature. We examined methods of measuring and reporting congruence to highlight variations impairing cross-study comparisons. Medline, PsychInfo, CINAHL, and Web of Science were systematically searched for clinical research studies examining patient preference and congruence as an outcome. Data were extracted into a matrix, including purpose, reported congruence, and method for eliciting preference. Studies were graded for quality. Using tables of preferred versus actual places of death, an overall congruence (total met preferences out of total preferences) and a kappa statistic of agreement were determined for each study. Twelve studies were identified. Percentage of congruence was reported using four different definitions. Ten studies provided a table or partial table of preferred versus actual deaths for each place. Three studies provided kappa statistics. No study achieved better than moderate agreement when analysed using kappa statistics. A study which elicited ideal preference reported the lowest agreement, while longitudinal studies reporting final preferred place of death yielded the highest agreement (moderate agreement). Two other studies of select populations also yielded moderate agreement. There is marked variation in methods of eliciting and reporting congruence, even among studies focused on congruence as an outcome. Cross-study comparison would be enhanced by the use of similar questions to elicit preference, tables of preferred versus actual places of death, and kappa statistics of agreement.

Decolorization and semi-batch continuous treatment of molasses distillery wastewater by Aspergillus tubingensis DCT6.

Large quantities of deeply pigmented molasses distillery wastewater (MDW), are discharged during the production of bio-ethanol from molasses. Conventional biological wastewater treatment is not effective in removing the molasses pigments. In the present study, a MDW treatment system was developed with combination treatment involving biodecolorization and biotreatment by Aspergillus tubingensis DCT6, together with physical decolorization by ozonation after treatment by activated sludge. A. tubingensis DCT6, which was isolated from soil, decolorized 44% of the pigments in MDW without adding any nutrients. The combination treatment with A. tubingensis DCT6 and activated sludge method (fungi-activated sludge treatment) removed about 90% of organic compounds from MDW and appears to reduce the amount of space and water required for treatment. The fungi-activated sludge treatment reduced the time needed for decolorization by ozone by 83%. Replacing fresh seed sludge at regular intervals was useful to maintain the dominance and decolorization ability of A. tubingensis DCT6. The entire treatment obtained a decolorization ratio of 89-94% and removed more than 90% of each of DOC, DTN, and DTP.

First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti-interferon-gamma autoantibodies.

This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti-interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti-IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Person-centered Feeding Care: A Protocol to Re-introduce Oral Feeding for Nursing Home Patients with Tube Feeding.

BACKGROUND: Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re-assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions. However, the literature contains little guidance on a systematic interdisciplinary team approach to the oral feeding reassessment of patients with TF, who are admitted to NHs. METHODS: This project had two parts that were conducted in one 170-bed intermediate/skilled, Medicare-certified NH in Honolulu, Hawai'i. Part 1 consisted of a retrospective observational study of characteristics of TF patients versus non-tube fed patients at NH admission (2003-2006) and longitudinal follow-up (through death or 6/30/2011) with usual care of the TF patients for outcomes of: feeding and swallowing reassessment, goals of care reassessment, feeding status (TF and/or per oral (PO) feedings), and hospice status. Part 2 involved the development of an interdisciplinary TF reassessment protocol through working group discussions and a pilot test of the protocol on a new set of patients admitted with TF from 2011-2014. RESULTS: Part 1: Of 238 admitted patients, 13.4% (32/238) had TF. Prior stroke and lack of DNR status was associated with increased likelihood of TF. Of the 32 patients with TF at NH admission, 15 could communicate and interact (mild, moderate or no cognitive impairment with prior stroke or pneumonia); while 17 were nonverbal and/or bedbound patients (advanced cognitive impairment or terminal disease). In the more cognitively intact group, 9/15 (60%) were never reassessed for tolerance of oral diets and 10/15 (66.7%) remained with TF without any oral feeding until death. Of the end-stage group, 13/17 (76.5%) did not have goals of care reassessed and remained with TF without oral feeding until death. Part 2: The protocol pilot project included all TF patients admitted to the facility in 2011-2014 (N=33). Of those who were more cognitively intact (n=22), 21/22 (95.5%) had swallowing reassessed, 11/22 (50%) resumed oral feedings but 11 (50%) failed reassessment and continued exclusive TF. Of those with end-stage disease (n=11), 100% had goals of care reassessed and 9 (81.8%) families elected individualized oral feeding (with or without TF). CONCLUSION: Using findings from our retrospective study of usual care, our NH's interdisciplinary team developed and pilot-tested a protocol that successfully reintroduced oral feedings to tube-fed NH patients who previously would not have resumed oral feeding.

The Associations of C-Reactive Protein with Serum Levels of Polyunsaturated Fatty Acids and Trans Fatty Acids Among Middle-Aged Men from Three Populations.

BACKGROUND: C-reactive protein (CRP) and many fatty acids (FAs) have been linked to cardiovascular disease. Associations of serum CRP with FAs in different populations have not been established. METHODS: Participants were 926 men aged 40-49 (2002-2006) from a population-based sample; 310 Whites from Pennsylvania, U.S., 313 Japanese from Shiga, Japan, and 303 Japanese Americans from Hawaii, U.S. Serum CRP (mg/L) was measured using immunosorbent assay while serum FAs (%) were measured using capillary-gas-liquid chromatography. RESULTS: Whites had CRP (mg/L) levels higher than Japanese with Japanese Americans in-between (age-adjusted geometric mean "GM" 0.96, 0.38, 0.66, respectively). Whites had also higher levels of total n-6 FAs (%) and trans fatty acids (TFAs) but lower levels of marine-derived n-3 FAs compared to Japanese (41.78 vs. 35.05, 1.04 vs. 0.58, and 3.85 vs. 9.29, respectively). Japanese Americans had FAs levels in-between the other two populations. Whites had significant inverse trends between CRP and tertiles of total n-6 FAs (GM 1.20, 0.91 and 0.80; p=0.002) and marine-derived n-3 FAs (GM 1.22, 1.00 and 0.72; p<0.001) but a significant positive trend with TFAs (GM 0.80, 0.95 and 1.15; p=0.007). Japanese had a significant inverse trend between CRP and only total n-6 FAs (GM 0.50, 0.35 and 0.31; p<0.001). Japanese Americans had CRP associations with n-3 FAs, n-6 FAs, and TFAs similar to but weaker than Whites. CONCLUSIONS: With the exception of consistent inverse association of CRP with total n-6 FAs, there are considerable variations across the three populations in the associations of CRP with different FAs.

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. MEASUREMENTS: For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. RESULTS: A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. CONCLUSION: Indicators of cerebral vascular pathology act differently on late life cognition.

The molten globule state of a chimera of human alpha-lactalbumin and equine lysozyme.

The molten globule state of equine lysozyme is more stable than that of alpha-lactalbumin and is stabilized by non-specific hydrophobic interactions and native-like hydrophobic interactions. We constructed a chimeric protein which is produced by replacing the flexible loop (residues 105-110) in human alpha-lactalbumin with the helix D (residues 109-114) in equine lysozyme to investigate the possible role of the helix D for the high stability and native-like packing interaction in the molten globule state of equine lysozyme. The stability of the molten globule state formed by the chimeric protein to guanidine hydrochloride-induced unfolding is the same as that of equine lysozyme and is substantially greater than that of human alpha-lactalbumin, although only six residues come from equine lysozyme. Our results also suggest that the non-native interaction in the molten globule state of alpha-lactalbumin changes to the native-like packing interaction due to helix substitution. The solvent-accessibility of the Trp residues in the molten globule state of the chimeric protein is similar to that in the molten globule state of equine lysozyme in which packing interaction around the Trp residues in the native state is partially preserved. Therefore, the helix D in equine lysozyme is one of the contributing factors to the high stability and native-like packing interaction in the molten globule state of equine lysozyme. Our results indicate that the native-like packing interaction can stabilize the rudimentary intermediate which is stabilized by the non-specific hydrophobic interactions.

Local and long-range interactions in the molten globule state: A study of chimeric proteins of bovine and human alpha-lactalbumin.

The molten globule state of alpha-lactalbumin has ordered secondary structure in the alpha-domain, which comprises residues 1 to 34 and 86 to 123. In order to investigate which part of a polypeptide is important for stabilizing the molten globule state of alpha-lactalbumin, we have produced and studied three chimeric proteins of bovine and human alpha-lactalbumin. The stability of the molten globule state formed by domain-exchanged alpha-lactalbumin, in which the amino acid sequence in the alpha-domain comes from human alpha-lactalbumin and that in the beta-domain comes from bovine alpha-lactalbumin, is the same as that of human alpha-lactalbumin and is substantially greater than that of bovine alpha-lactalbumin. Therefore, our results show that the stability of the molten globule state of alpha-lactalbumin is determined by the alpha-domain and the beta-domain is not important for stabilizing the molten globule state. The substitution of residues 1 to 34 of bovine alpha-lactalbumin with those of human alpha-lactalbumin substantially increases the stability of the molten globule state, while the substitution of residues 86 to 123 of bovine alpha-lactalbumin with those of human alpha-lactalbumin decreases the stability of the molten globule state. Therefore, residues 1 to 34 in human alpha-lactalbumin is more important for the stability of the human alpha-lactalbumin molten globule state than residues 86 to 123. The stabilization of the molten globule state due to substitution of both residues 1 to 34 and 86 to 123 is not identical with the sum of the two individual substitutions, demonstrating the non-additivity of the stabilization of the molten globule state. This result indicates that there is a long-range interaction between residues 1 to 34 and 86 to 123 in the molten globule state of human alpha-lactalbumin. The differences in the stabilities of the molten globule states are well correlated with the averaged helical propensity values in the alpha-domain when the long-range interactions are negligible, suggesting that the local interaction is the dominant term for determining the stability of the molten globule state. Our results also indicate that the apparent cooperativity is closely linked to the stability of the molten globule state, even if the molten globule state is weakly cooperative.

Crystallization and preliminary X-ray diffraction study of ferrocytochrome c2 from Rhodopseudomonas viridis.

Crystals of ferrocytochrome c2 from a non-sulphur purple photosynthetic bacterium, Rhodopseudomonas viridis, have been grown from ammonium sulphate solution at pH 8.5 by the sitting-drop vapour-diffusion procedure. The crystals belong to the trigonal system, space group P3(1)21 (or its enantiomorph P3(2)21) with unit-cell dimensions of a = b = 75.8 A and c = 40.1 A, and diffract to at least 2.0 A resolution. Assuming that an asymmetric unit contains one protein molecule (approx. 12,300 Mr), the solvent content of the crystal is approximately 54.5% (v/v).

The detection of dementia in the primary care setting.

BACKGROUND: Recognition and medical record documentation of dementia in the primary care setting are thought to be poor. To our knowledge, previous studies have not examined these issues in private practice office settings within the United States. OBJECTIVE: To determine the rate of unrecognized and undocumented dementia in a primary care internal medicine private practice. METHODS: This was a cross-sectional study of 297 ambulatory persons aged 65 years and older attending an internal medicine private group practice within an Asian American community of Honolulu, Hawaii. Of the subjects, 95% had been with their current primary care physician for at least 1 year. Each subject's primary care physician noted the presence or absence of dementia by questionnaire at the time of an office visit. An investigating physician (V.G.V.) subsequently assessed cognitive function using the Cognitive Abilities Screening Instrument, and confirmed the presence of dementia and its severity, if present, using Benson and Cummings' criteria and the Clinical Dementia Rating Scale, respectively. A trained research assistant completed telephone interviews to proxy informants for collateral information concerning cognition, behavior, and occupational or social function. Subjects' outpatient medical records were reviewed for documentation of problems with cognition. RESULTS: Twenty-six cases of dementia were identified. Of these 26, 17 (65%) (95% confidence interval, 44.3-82.8) were not documented in outpatient medical records; of 18 patients, 12 (67%) (95% confidence interval, 40.9-86.7) were not thought to have dementia by their physicians at the time of the office visit. Recognition and documentation rates increased with advancing stage of disease. CONCLUSION: Dementia is often unrecognized and undocumented in private practice settings. Arch Intern Med. 2000;160:2964-2968

Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. The SHEP Cooperative Research Group.

BACKGROUND: There are scant data on the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) on cardiovascular events and death in older patients with hypertension. OBJECTIVE: To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke. PATIENTS: Participants were 3975 men and women (mean age, 71 years) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial, a randomized, double-blind, placebo-controlled clinical trial of lowdose antihypertensive therapy, with follow-up for 5 years. MAIN OUTCOME MEASURES: Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses. RESULTS: There was no statistically significant relation of death or stroke with BMI in the placebo group (P = .47), and there was a U- or J-shaped relation in the treatment group. The J-shaped relation of death with BMI in the treated group (P = .03) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6; the curve was quite flat for women across a wide range of BMIs. For stroke, men and women did not differ, and the BMI nadir for both sexes combined was 29, with risk increasing steeply at BMIs below 24. Those in active treatment, however, had lower death and stroke rates compared with those taking placebo. CONCLUSIONS: Among older patients with hypertension, a wide range of BMIs was associated with a similar risk of death and stroke; a low BMI was associated with increased risk. Lean, older patients with hypertension in treatment should be monitored carefully for additional risk factors.

The Statistical Modeling of Aging and Risk of Transition Project: Data Collection and Harmonization Across 11 Longitudinal Cohort Studies of Aging, Cognition, and Dementia.

Longitudinal cognitive trajectories and other factors associated with mixed neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular disease) remain incompletely understood, despite being the rule and not the exception in older populations. The Statistical Modeling of Aging and Risk of Transition study (SMART) is a consortium of 11 different high-quality longitudinal studies of aging and cognition (N=11,541 participants) established for the purpose of characterizing risk and protective factors associated with subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While brain donation was not required for participation in all SMART cohorts, most achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies comprising SMART have large numbers of participants who were followed from intact cognition and transitioned to cognitive impairment and dementia, as well as participants who remained cognitively intact until death. These data provide an exciting opportunity to apply sophisticated statistical methods, like Markov processes, that require large, well-characterized samples. Thus, SMART will serve as an important resource for the field of mixed dementia epidemiology and neuropathology.

Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study.

BACKGROUND AND PURPOSE: The aim of this study was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. METHODS: The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high SBP/no epsilon4; high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test. RESULTS: After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI >/=82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors. CONCLUSIONS: The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.

Association of body mass index with blood pressure in elderly Japanese American men. The Honolulu Heart Program.

Few data are available on the association between body mass index (BMI) and blood pressure in elderly individuals, particularly among minority groups. We studied the cross-sectional association of BMI with systolic and diastolic pressures in 1378 Japanese American men 60 to 82 years of age who were participants in the population-based Third Lipoprotein Examination of the Honolulu Heart Program conducted between 1980 and 1982. When the subjects were divided into 5-year age groups, mean BMI decreased linearly with increasing age. Mean systolic pressure rose from 134.8 mm Hg in the first quintile of BMI to 138 in the second and 141.8 in the third quintiles, with levels of 139.2 and 142 in the fourth and fifth quintiles, respectively (test for trend, P = .083). Mean diastolic pressure rose from 78.1 mm Hg in the lowest quintile of BMI to 83.9 in the highest (test for trend, P = .008). We performed multiple regression analysis, controlling for factors known to influence blood pressure values, including age, physical activity index, alcohol intake, current smoking status, and diabetes mellitus. The association between BMI and both systolic and diastolic pressures remained highly statistically significant in these analyses. These results show that obesity and high blood pressure continue to be highly correlated even in old age and suggest that it may be possible to modify rates of hypertension by changes in body weight.