The association between obesity and dementia has been inconsistent, possibly due to changes in body composition often seen in old age. Leptin may be associated with better cognitive function. However, neuroprotection may be inhibited among obese subjects possibly due to leptin resistance. We sought to determine (i) if leptin is associated with risk of dementia or mild cognitive impairment (MCI) in a cohort of very old women, (ii) if this association is modified by obesity, and (iii) if leptin is a stronger risk factor compared with traditional anthropometric measures.
We studied 579 older women (mean age 82.6 years) from the ongoing prospective cohort Study of Osteoporotic Fractures, who were dementia-free at year-16 examination (our study baseline). Leptin (ng/mL) was measured using year-16 frozen serum, and anthropometric measures were collected during the same visit. Diagnosis of dementia/MCI was determined at year-20 examination.
There was evidence for a multiplicative interaction between log leptin and categorical body mass index (p = .03). Among women with body mass index <25kg/m2 (n = 190), 1SD difference in log leptin (0.91ng/mL) was associated with 32% lower odds of dementia/MCI (OR = .68; 95% CI = .46, .99), after adjustment. The association was not significant among women with body mass index ≥25kg/m2 (n = 377). Traditional anthropometric measures such as weight, height, and body mass index were not associated with dementia/MCI.
In this cohort of very old women, higher serum leptin was prospectively associated with lower odds of dementia/MCI in women with normal body mass index, but not in overweight or obese women. Leptin may be a better predictor of dementia/MCI than traditional anthropometric measures.
Dementia; Elderly; Leptin; Obesity
We examined whether acculturation and immigrant generation, a marker for assimilation, are associated with diabetes risk in an aging Mexican-origin population.
We analyzed data on 1789 adults aged 60 to 101 years from the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the basis of diabetic medication use, self-report of physician diagnosis, or a fasting glucose of 126 milligrams/deciliter or greater. Logistic regression modeled prevalent diabetes.
Adjusting for age and gender, we observed significant but divergent associations between immigrant generation, acculturation, and diabetes risk. Relative to first-generation adults, second-generation adults had an odds ratio (OR) of 1.8 (95% confidence interval [CI] = 1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of having diabetes. Greater US acculturation, however, was associated with a slightly decreased diabetes rate. In the full model adjusting for socioeconomic and lifestyle factors, the association between generation (but not acculturation) and diabetes remained significant.
Our study lends support to the previously contested notion that assimilation is associated with an increased diabetes risk in Mexican immigrants. Researchers should examine the presence of a causal link between assimilation and health more closely.
Chronic kidney disease (CKD) is diagnosed by serum creatinine, which is biased by muscle mass, age and race. We evaluated whether cystatin C, an alternative measure of kidney function, can detect high risk CKD among elderly Mexican-Americans.
Sacramento Area Study of Latinos (SALSA)
1,435 Mexican-Americans ages 60–101 with mean follow-up 6.8 years
We estimated glomerular filtration rate (eGFR, ml/min/1.73m2)by creatinine and cystatin C, and classified persons into four mutually exclusive categories: (1) CKD neither (eGFRcreat ≥60 and eGFRcys ≥60); (2) CKD creatinine only (eGFRcreat <60 but eGFRcys ≥60); (3) CKD cystatin only (eGFRcreat ≥60 but eGFRcys <60); and (4) CKD both (eGFRcreat <60 and eGFRcys <60). We studied the association of each CKD classification with all-cause death and cardiovascular (CVD) death using Cox regression.
At baseline, mean was age 71±7; 34% (N=481) were diabetic and 68% (N=980) hypertensive. Compared with persons with no CKD by either marker, persons with CKD both had the highest risks for death (HR 2.30, 1.78–2.98) and CVD death (HR 2.75, 1.96–3.86) after full adjustment. Persons with CKD by cystatin C only were also at increased risk for death, HR 1.91 (1.37–2.67) and for CVD death, HR 2.56 (1.64–3.99)) compared to no CKD. In contrast, persons with CKD by creatinine only were not at increased risk for CVD death (HR 1.39, 0.71–2.72), but remained at higher risk for all-cause death (HR 1.95, 1.27–2.98).
Cystatin C may be a useful alternative in addition to creatinine to detect high risk CKD in elderly Mexican Americans.
chronic kidney disease; Mexican-Americans; elderly; creatinine; cystatin C; cardiovascular disease
Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life.
We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60–100 years in 1998–1999.
Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families.
Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment.
Acculturation; Cognition; Epidemiology; Life course and developmental change
In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status.
Participants were 1,562 Latino adults aged 60–101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records.
There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06).
In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.
Blood pressure; Functional status; Latinos
The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elders are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster, but not slower, walking older adults.
Participants included 2,340 persons ≥65 years in the National Health and Nutrition Examination Survey, 1999–2000 and 2001–2002. Mortality data was linked to death certificates in the National Death Index. Walking speed was measured over a 20-foot walk and classified as faster (≥ 0.8 meters/second, n=1,307), slower (n=790), or incomplete (n=243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medications.
There were 589 deaths through December 31st, 2006. The association of BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (≥140 mmHg) had a greater adjusted risk of mortality compared to those without (Hazard Ratio (HR): 1.35, 95% confidence interval (CI): 1.03, 1.77). Among slower walkers, neither elevated systolic nor diastolic BP (≥90 mmHg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR: 0.38, 95% CI: 0.23, 0.62 (systolic) and HR: 0.10, 95% CI: 0.01, 0.81 (diastolic).
Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.
Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican-Americans have higher levels of obesity than Non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association.
We analyzed 1480 dementia-free older Mexican-Americans who were followed over ten years. Cognitive function was assessed every 12 to 15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT).
For females with small waist circumference (≤35inches), an interquartile range (IQR) difference in leptin was associated with 35% less 3MSE errors and 22% less decline in SEVLT score over 10 years. For males with small waist circumference (≤40inches), an IQR difference in leptin was associated with 44% less 3MSE errors and 30% less decline in SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with large waist circumference.
Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function.
Aging; cognition; obesity; leptin; longitudinal study; Mexican Americans
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.
RESEARCH DESIGN AND METHODS
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
The association between body adiposity at older ages and the development of cognitive impairment is unclear.
The association of body mass index (BMI) and waist circumference in late life with incidence of cognitive impairment was prospectively examined in a cohort study of 1,351 Latinos, aged 60–101 and residents of the Sacramento, CA, area at study baseline. The status of dementia and “cognitive impairment but not demented” (CIND) was determined at baseline and at each of five follow-up examinations by a multistage assessment protocol. Incident cases of dementia and CIND were combined (dementia/CIND) for more than 8 years of follow-up. BMI was categorized as less than 25.0, 25.0–29.9 (overweight), and 30 kg/m2 or greater (obese). Waist circumference was categorized into sex-specific tertiles.
Dementia/CIND was diagnosed in 110 (8.2%) participants. Compared with the lowest BMI category, overweight participants had a 48% decreased rate of dementia/CIND (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.30–0.91) and obese participants had a 61% decreased rate of dementia/CIND (HR = 0.39, 95% CI: 0.20–0.78). Rates of dementia/CIND for the middle and high tertile of waist circumference, compared with the low tertile, were 80% and 90% higher, respectively (adjusted HR = 1.8, 95% CI: 1.1–3.1, and adjusted HR = 1.9, 95% CI: 0.91–3.8).
Abdominal fat in late life appears to confer an increased risk for dementia/CIND, whereas overall obesity appears to be protective. This may reflect age-related changes in body composition and the association of visceral fat with metabolic dysregulation.
Adiposity; Dementia; Cognitive impairment; Body mass index; Waist circumference
Those with an apolipoprotein APOE4 allele (APOE4) have lower C-reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer’s disease (AD) is not established.
All cause dementia and cognitive impairment without dementia (CIND) was determined over five follow up visits from 1998–2006 in an ongoing cohort of older Latinos. The association between high sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer’s disease by APOE4 status was examined in semi-parametric survival models with covariate adjustments.
CRP was significantly lower among those with APOE4 than in those without. Among those with APOE4, CRP was associated with lower rates of combined dementia/CIND (HR: 0.60, 95% CL: 0.20–0.91, p=0.03) from a fully adjusted model. Among those with no APOE4, there was no effect of CRP on dementia/CIND rates (HR: 0.94, 95% CL:0.67–1.33).
Lower CRP in those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in those with APOE4 may be a marker of better immune function, leading to lower rate of dementia and AD.
Apolipoprotein E; c-reactive protein; cognitive impairment; dementia incidence; Latino aging
There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making.
Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved.
Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.
The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.
Comparative effectiveness research; Effectiveness guidance document; Acupuncture
In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = −0.033; P < 0.05) and rates of decline (β = −0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.
aging; cognition; education; Mexican Americans; residence characteristics
To examine the associations between life-course education and late-life cognitive function along with the modifying role of migration history.
The combined sample includes 1,789 participants from the Sacramento Area Latino Study on Aging and 5,253 participants from the Mexican Health and Aging Study. Aged 60+ at baseline, participants were classified as Mexican residents, Mexicans-return migrants, Mexicans-immigrants to the US, and Mexicans-US-born. Cognitive function was measured using standardized z-scores of a short-term verbal recall test. Multivariate linear regression analysis was conducted.
Participants’ z-scores were higher among those whose mother had more than elementary education (β=0.28, p<0.05). Participant’s education mediated this association. For 5-year difference in education, the cognitive z-score increased by 0.3 points for a US-born. Results were similar with father’s education.
Adult educational attainment mediates the effect of childhood socioeconomic status on late-life cognition. Migration plays a role in shaping cognitive aging.
cognition; health; education; life course; old age; Mexican Americans
There have been few investigations of the link between changes in life-course socioeconomic position (SEP) and cognitive decline or incidence of dementia. The authors examined the impact of changes in life-course SEP on incidence of dementia and cognitive impairment but not dementia (CIND) over a decade of follow-up. Participants of Mexican origin (n = 1,789) were members of the Sacramento Area Latino Study on Aging cohort. Incidence of dementia/CIND was ascertained by using standard diagnostic criteria. SEP indicators at 3 life stages (childhood, adulthood, and midlife) were used to derive a measure of cumulative SEP (range, 0 to 8) and SEP mobility. Nearly 24% of the sample maintained a low SEP throughout life. Hazard ratios and 95% confidence intervals were computed from Cox proportional hazards regression models. In fully adjusted models, participants with a continuously high SEP had lower hazard ratios for dementia/CIND compared with those with a continuously low SEP at all 3 life stages (hazard ratio = 0.49, 95% confidence interval: 0.24, 0.98; P = 0.04). In age-adjusted models, participants experienced a 16% greater hazard of dementia/CIND with every 1-unit increase in cumulative SEP disadvantage across the life course (hazard ratio = 1.16, 95% confidence interval: 1.01, 1.33; P = 0.04). Early exposures to social disadvantage may increase the risk of late-life dementia.
aged; dementia; longitudinal studies; Mexican Americans; social class; socioeconomic factors
Population studies strive to determine the prevalence of Alzheimer dementia but prevalence estimates vary widely. The challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer’s disease (AD) are reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD are considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies as may occur should a plasma biomarker be developed. Biomarkers for AD also could facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in “mixed dementia”.
To evaluate safety of intravenous tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams.
This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations.
Two hundred seventy-three consecutive stroke patients were treated by 95 emergency physicians using guidelines and local neurology resources. One-year mortality was 27.8%. Unadjusted Cox model relative risk of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. Rate of significant ICH by computed tomography criteria was 6.6% (OR 1.03, 95% CI = 0.56 to 1.90 compared to NINDS tPA treatment group). The proportion of symptomatic ICH by two other pre-specified sets of clinical criteria was 4.8% and 7.0%. Rate of any ICH within 36 hours of treatment was 9.9% (relative risk [RR] 0.94, 95% CI = 0.58 to 1.51 compared to NINDS tPA group). Occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS < 2. Guideline deviations occurred in the ED in 26% of patients and in 25% of patients following admission.
In these EDs there was no evidence of increased risk with respect to mortality, ICH, systemic hemorrhage, or worsened functional outcome when tPA was administered without dedicated thrombolytic stroke teams. Additional effort is needed to improve guideline compliance.
Stroke; tissue plasminogen activator; safety; emergency department; ICH
The objective of this study was to examine whether cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and C-reactive protein (CRP) are associated with functional impairment in older Latinos.
A cross-sectional analysis of a cohort study conducted with a community dwelling elderly population. The sample was a subset (N = 1507/1789) of participants in the Sacramento Area Latino Study on Aging (SALSA) ages 60–101 with available serum samples and functional impairment measures. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. Several measures were used to assess functional impairment, including activities of daily living (ADL), instrumental activities of daily living (IADL), and walking pace.
CMV and CRP showed statistically significant graded associations with ADL functional impairment, even after controlling for age and gender. The relationship between CMV and ADL was slightly attenuated, and the confidence interval contained the null value when adjusted for total number of health conditions, body mass index, and household income. Only high levels of CRP were significantly related to ADL and IADL impairment even after adjusting for all other covariates.
Inflammation is clearly linked to physical functioning among aging Latinos. This study also suggests a role for CMV infection in relation to ADL impairment. Further research examining the influence of infection, immune response, and inflammation on longitudinal trajectories of physical functioning is warranted.
Cytomegalovirus (CMV); CRP; Latinos; Physical function; Community
Lower socioeconomic position (SEP) is related to higher prevalence of Type 2 diabetes, yet little is known about the relationship of SEP with incident diabetes.
The association between SEP, measured by self-reported education, income, and occupation, and Type 2 diabetes incidence was examined in a community sample of 6147 diabetes-free adults from Alameda County, CA. Cox proportional hazards models estimated the effect of baseline (1965) and time-dependent (value changes over time) measures of SEP on incident diabetes over a 34-year study period (1965–99). Demographic confounders (age, gender, race, and marital status) and potential components of the causal pathway (physical inactivity, smoking, alcohol consumption, body composition, hypertension, depression, and health care access) were included as fixed or time-dependent covariates.
Education, income, and occupation were associated with increased diabetes risk in unadjusted models. In baseline models adjusted for demographics, respondents with <12 years of education had 50% excess risk compared with those with more education [hazard ratio (HR) = 1.5, 95% confidence interval (95% CI) 1.11–2.04], but income and occupation were no longer significantly associated with increased risk. Further adjustment minimized the significance of all associations. Time-dependent effects were consistently elevated for low education and male blue-collar occupation, but non-significant after full adjustment (HR = 1.1, 95% CI 0.79–1.47 and HR = 1.3, 95% CI 0.91–1.89, respectively).
Socioeconomic disadvantage, especially with low educational attainment, is a significant predictor of incident Type 2 diabetes, although associations were largely eliminated after covariate adjustment. Obesity and overweight appear to mediate these associations.
Socioeconomic factors; Type 2 diabetes mellitus; incidence
To determine baseline proportion of emergency physicians with favorable attitudes and beliefs toward IV tPA use in a cohort of randomly selected Michigan hospitals.
278 emergency physicians from 24 hospitals were surveyed. A confidential, self-administered, pilot-tested survey assessing demographics, practice environment, attitudes and beliefs regarding tPA use in stroke was used. Main outcome measures assessed belief in legal standard of care, likelihood of use in ideal setting, comfort in use without a specialist consultation and belief that science on tPA use is convincing. OR with robust 95% CI (adjusted for clustering) were calculated to quantify the association between responses and physician- and hospital-level characteristics.
199 surveys completed (gross response rate 71.6%). 99% [95% CI: 97.8 to 100] indicated use of tPA in eligible patients represented either acceptable or ideal patient care. 27% [95% CI: 21.7 to 32.3] indicated use of tPA represented a legal standard of care. 83% [95% CI: 78.5 to 87.5] indicated they were “likely” or “very likely” to use tPA given an ideal setting. When asked about using tPA without a consultation, 65% [95% CI: 59.3 to 70.7], indicated they were uncomfortable. 49% [95% CI: 43.0 to 55.0] indicated the science regarding use of tPA in stroke is convincing, with 30% remaining neutral. Characteristics associated with favorable attitudes included: non-emergency medicine board certification; older age and a smaller hospital practice environment.
In this cohort, emergency physician attitudes and beliefs toward IV tPA use in stroke are considerably more favorable than previously reported.
Stroke; Emergency medicine; Attitude; Belief; Thrombolytic Therapy
This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60–101 years) in California followed in 1998–2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.
cardiovascular diseases; cytomegalovirus; immune system; infection; inflammation
The Pro12Ala polymorphism in the PPAR-γ gene has been associated with reduced incidence of type 2 diabetes. Although diabetes has been implicated as a risk factor for dementia, the association of Pro12Ala with cognitive impairment is unclear. Dementia and cognitive impairment without dementia (CIND) were determined during six annual follow-up evaluations in a cohort of 929 older Latinos. Among those with diabetes at baseline, there was an increased rate of dementia/CIND for Ala carriers compared to non-carriers (adjusted hazard ratio (HR) = 2.5, 95% confidence interval (CI): 1.3–4.9) but not among non-diabetic participants (adjusted HR=0.94; 95% CI: 0.49–1.8). Among males, there was also an increased rate for Ala carriers (adjusted HR= 2.7, 95% CI: 1.4–5.2) but not among female carriers (adjusted HR = 0.88; 95% CI: 0.47–1.6). The rate of dementia/CIND was highest in diabetic male Ala carriers (adjusted HR= 4.2; 95% CI: 1.5–11) compared to non-diabetic male carriers (adjusted HR=2.9; 95% CI: 1.1–7.4), diabetic female carriers (HR=1.6; 95% CI: 0.66–4.1), and non-diabetic female carriers (HR=0.52; 95% CI: 0.21–1.3). These data suggest that although the Ala variant is associated with a reduced risk of type 2 diabetes, it may increase the risk of cognitive impairment in individuals once diabetes has developed. Male Ala carriers may also have a greater risk of dementia/CIND.
Pro12Ala genotype; cognitive impairment; dementia
Use of alteplase improves outcome in some patients with stroke. Several types of barrier frequently prevent its use. We assessed whether a standardised, barrier-assessment, multicomponent intervention could increase alteplase use in community hospitals in Michigan, USA.
In a cluster-randomised controlled trial, we selected adult, non-specialty, acute-care community hospitals in the Lower Peninsula of Michigan, USA. Eligible hospitals discharged at least 100 patients who had had a stroke per year, had less than 100 000 visits to the emergency department per year, and were not academic comprehensive stroke centres. Using a computer-generated randomisation sequence, we selected 12 matched pairs of eligible hospitals. Within pairs, the hospitals were allocated to intervention or control groups with restricted randomisation in January, 2007. Between January, 2007, and December, 2007, intervention hospitals implemented a multicomponent intervention that included qualitative and quantitative assessment of barriers to alteplase use and ways to address the findings, and provided additional support. The primary outcome was change in alteplase use in patients with stroke in emergency departments between the pre-intervention period (January, 2005, to December, 2006) and the post-intervention period (January, 2008, to January, 2010). Physicians in participating hospitals and the coordinating centre could not be masked to group assignment, but were masked to progress made in paired control hospitals. External medical reviewers who were masked to group assignment assessed outcomes. We did intention-to-treat (ITT) and target-population (without one pair that was excluded after randomisation) analyses. This trial is registered at ClinicalTrials.gov, number NCT00349479.
All 24 hospitals completed the study. Overall, 745 of 40 823 patients with stroke received intravenous alteplase treatment. In the ITT analysis, the proportion of patients with stroke who were admitted and treated with alteplase increased between the pre-intervention and post-intervention periods in intervention hospitals (89 [1·25%] of 7119 patients to 235 [2·79%] of 8419) to a greater extent than in control hospitals (99 [1·25%] of 7946 to 194 [2·10%] of 9222), but the difference between groups was not significant (relative risk [RR] 1·37, 95% CI 0·96–1·93; p=0·08). In the target-population analysis, the increase in alteplase use in intervention hospitals (59 [1·00%] of 5882 to 191 [2·62%] of 7288) was significantly greater than in control hospitals (65 [1·09%] of 5957 to 120 [1·72%] of 6989; RR 1·68, 95% CI 1·09–2·57; p=0·02), but was still clinically modest.
The intervention did not significantly increase alteplase use in patients with ischaemic stroke. The increase in use of alteplase in the target population was significant, but smaller than the effect to which the study was powered. Additional strategies to increase acute stroke treatment are needed.