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Context: The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.Objective: To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults.Design, Setting, and Participants: The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.Intervention: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing placebo (n = 1524).Main Outcome Measures: Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.Results: Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P > .05).Conclusion: Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.Trial Registration: clinicaltrials.gov Identifier: NCT00010803. [ABSTRACT FROM AUTHOR]

Objective: To compare rates of mild cognitive impairment (MCI) and rates of progression to dementia using different MCI diagnostic systems.Methods: MCI was investigated at baseline in 3063 community dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every 6 months to identify the presence of dementia. Overall MCI frequency was determined using (1) a Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests.Results: 40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic MCI = 16.6%). 15.7% were classified as MCI by both criteria and 47.4% as normal by both. Discordant diagnoses were observed in 24.5% who met NP normal/CDR MCI and in 12.4% who met NP MCI/CDR normal. Factors associated with CDR MCI among NP normal included lower education, lower NP scores, more instrumental activities of daily living impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow-up of 6.1 years than those meeting NP normal/CDR MCI.Conclusions: Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by the NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate shared and unique risk factors for maintaining physical and cognitive function into the ninth decade and beyond. DESIGN: Longitudinal cohort study. SETTING: Four U.S. communities. PARTICIPANTS: One thousand six hundred seventy-seven participants in the Cardiovascular Health Study All Stars Study, assessed in 2005/06. Median age was 85 (range 77-102), 66.5% were women, and 16.6% were black. MEASUREMENTS: Intact function was defined as no difficulty with any activities of daily living and a score of 80 or higher on the Modified Mini-Mental State Examination. Baseline characteristics assessed in 1992/93 included demographics, behavioral health factors, chronic disease history, subclinical disease markers, cardiovascular risk factors, and inflammatory markers. Multinomial logistic regression was used to compare risk for physical disability, cognitive impairment,and combined impairments with no functional impairment. RESULTS: Of the 1,677 participants evaluated in both domains, 891 (53%) were functionally intact. Continuous measures of function, including the Digit Symbol Substitution Test and gait speed, showed that all groups, including the most functional, had declined over time. The functional group had less decline but also tended to have higher starting values. Functional individuals had a higher baseline health profile than those with either or cognitive impairment or both impairments combined. Women and individuals with greater weight had higher rates of physical impairment but not cognitive impairment. Risk factors common to both types of impairment included cardiovascular disease and hypertension. CONCLUSION: Intact function was found in only approximately half of these older adults in the ninth decade and beyond. High baseline function and low vascular disease risk characterized functional aging. [ABSTRACT FROM AUTHOR]

Context: Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking.Objective: To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI).Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed every 6 months for incident dementia.Intervention: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or placebo (n = 1524).Main Outcome Measures: Incident dementia and AD determined by expert panel consensus.Results: Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G. biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G. biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G. biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39).Conclusions: In this study, G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials.gov Identifier: NCT00010803. [ABSTRACT FROM AUTHOR]

OBJECTIVE. To compare the characteristics of older women who did and did not have screening mammograms and Pap smears during the first two years both services were a Medicare Part B benefit. METHODS. A prospective study was conducted in five rural Pennsylvania counties of 2205 female community-dwelling Medicare Part B beneficiaries who volunteered to participate in a Medicare prevention demonstration project. The baseline health risk appraisal included information on demographics, insurance status, disease history, symptomatology, and functional and cognitive status. These variables were tested for their association with the use of mammography and Pap smear using Medicare utilization claims data from 1991 to 1992. RESULTS. Of 2175 women still alive after three years, 44.6% had had a mammogram and 14.6% had had a Pap smear in either 1991 or 1992. Multivariate logistic regression revealed that women were more likely to have a mammogram if they were younger, were more educated, had supplemental insurance, did not need assistance with activities of daily living, and did not have diabetes or arthritis. Younger, college educated, and non-widowed women were more likely to have Pap smears than women in other categories. CONCLUSIONS. With cost less of a barrier, more aggressive efforts to persuade older women to have mammograms and Pap smears must be developed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Data from randomized clinical trials in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease. In view of these findings, we examined mortality from coronary heart disease among patients with early stage breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy.Methods: Deaths occurring among women who were randomly assigned to 5 years of either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to determine the cause. Three categories of heart disease-related death were defined: 1) death from a definite fatal myocardial infarction, 2) death from definite fatal coronary heart disease/possible myocardial infarction, and 3) death from possible fatal coronary heart disease. Comparisons of the findings by treatment group were made on the basis of average annual hazard (i.e., death) rates and the corresponding relative hazard of death.Results: The average annual death rate from coronary heart disease was lower for patients who received tamoxifen than for patients who received placebo, but the difference was not statistically significant. There were eight definite heart-related deaths (i.e., definite fatal myocardial infarction or definite fatal coronary heart disease/possible myocardial infarction) among the patients who received tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were 12 definite heart-related deaths among the patients who received placebo, yielding an average annual rate of 0.94 per 1000. The corresponding relative hazard of death from definite fatal heart disease (tamoxifen versus placebo) was 0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group and 10 deaths in the placebo group were classified as possible cases of fatal coronary heart disease. When these cases and the definite cases were considered together, the average annual death rate for the patients who received tamoxifen was 1.48 per 1000, and the rate for the patients who received placebo was 1.73 per 1000. The corresponding relative hazard of death was 0.85 (95% confidence interval = 0.46-1.58).Conclusions: The findings from the B-14 trial are consistent with the findings from the Scottish and the Swedish trials, suggesting that tamoxifen treatment reduces coronary heart disease among patients with breast cancer. Continued follow-up of the patients in these trials and in ongoing prevention trials is needed to accumulate enough data so that reliable conclusions can be drawn about the benefits of tamoxifen in preventing heart disease. [ABSTRACT FROM AUTHOR]

Background Intensive systolic blood pressure treatment (<120 mm Hg) in SPRINT (Systolic Blood Pressure Intervention Trial) improved survival compared with standard treatment (<140 mm Hg) over a median follow-up of 3.3 years. We projected life expectancy after observed follow-up in SPRINT using SPRINT-eligible participants in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study). Methods and Results We used propensity scores to weight SPRINT-eligible NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (<4 years) using a time-based flexible parametric survival model. In SPRINT-eligible NHLBI-PCS participants, we estimated posttrial survival (≥4 years) using an age-based flexible parametric survival model and applied the formula to SPRINT participants to predict posttrial survival. We projected overall life expectancy for each SPRINT participant and compared it to parametric regression (eg, Gompertz) projections based on SPRINT data alone. We included 8584 SPRINT and 10 593 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.2 (8.8) years, and 35.5% and 37.6% were women in SPRINT and NHLBI-PCS, respectively. Using the NHLBI-PCS-based method, projected mean life expectancy from randomization was 21.0 (7.4) years with intensive and 19.1 (7.2) years with standard treatment. Using the Gompertz regression, life expectancy was 11.2 (2.3) years with intensive and 10.5 (2.2) years with standard treatment. Conclusions Combining SPRINT and NHLBI-PCS observed data likely offers a more realistic estimate of life expectancy than parametrically extrapolating SPRINT data alone. These results offer insight into the potential long-term effectiveness of intensive SBP goals.

Introduction: Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects., Methods: We examined baseline plasma β-amyloid (Aβ) levels in relationship to incident dementia during a period of 8.5 years in 2840 subjects age >75 years; 2381 were cognitively normal (CN) and 450 mild cognitive impairment., Results: Increased plasma Aβ1-40 and Aβ1-42 levels were associated with gender (women), age, low education, creatinine levels, history of stroke, and hypertension. CN participants who developed dementia had lower levels of Aβ1-42 and Aβ1-42/Aβ1-40 ratio compared with those who did not. Aβ levels did not predict dementia in mild cognitive impairment participants., Discussion: There was an inverse association between Aβ1-42 and Aβ1-42/Aβ1-40 ratio to risk of dementia in CN participants. Cerebral and cardiovascular disease and renal function are important determinants of increased Aβ levels and must be considered in evaluations of relationship of plasma Aβ and subsequent risk of dementia., (Copyright © 2019. Published by Elsevier Inc.)

Background: Blood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified., Objective: The authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures., Methods: The authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke., Results: A total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk., Conclusions: Cumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: There is a consensus that social connectedness is integral for a long, healthy life. However, studies of social support and survival have primarily relied on baseline social support measures, potentially missing the effects of fluctuations of perceived support over time. This is especially important for older adults who experience increased changes in disability. This study examined whether among older adults time-varying perceived social support was associated with time to death (main effect model of support) and whether time-varying disability was a modifier (stress-buffering model of support). Gender and marital status were also examined as modifiers., Methods: Older adults in the Cardiovascular Health Study ( N = 5,201) completed self- report measures of demographics and psychological health and clinical risk factors for mortality at baseline (1989-1990). Perceived social support and disability were measured from baseline through Wave 11 (1998-1999). Cox regression of time to death with time-varying covariates was performed., Results: Time-varying as well as baseline-only perceived social support was associated with greater survival in the unadjusted models but not after adjustment. Gender, marital status, and time-varying disability were not significant modifiers., Conclusions: In contrast with the previously reported association between baseline individual differences in perceived social support and time to death, older adults' baseline-only and fluctuating perceptions of perceived support over time were not associated with time to death after adjustment for other clinical physical and psychological risk factors. Research is needed to identify other relationship factors that may be more informative as time-varying predictors of health and longevity in large longitudinal data sets. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo., Methods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed., Results: Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56)., Conclusions: Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).

Objectives: To understand which causes of death are higher in black than white community-dwelling older adults and determine whether differences in baseline risk factors explain racial differences in mortality., Design: Longitudinal cohort study (Health, Aging, and Body Composition Study)., Setting: Pittsburgh, Pennsylvania; and Memphis, Tennessee., Participants: Black and white men and women aged 70 to 79 during recruitment (N=3,075; 48% men, 42% black) followed for a median of 13 years., Measurements: A committee of physicians adjudicated cause of death, which was categorized as cardiovascular disease (CVD), stroke, cancer, dementia, pulmonary, infection, kidney, or other causes. Using competing risks regression, we examined whether known risk factors at baseline (demographic characteristics, smoking, body mass index, chronic diseases, physical function, cognition) could explain racial differences in cause-specific mortality risk., Results: During follow-up, 1,991 (65%) participants died. Black participants died at higher rates from cancer (hazard ratio (HR)=1.36, 95% confidence interval (CI)=1.14-1.63), kidney disease (HR=2.09, 95% CI=1.16-3.74), stroke (HR=1.31, 95% CI=0.98-1.76); and CVD (HR=1.16, 95% CI=0.98-1.37). Poorer physical and cognitive performance at baseline among black participants explained most of the racial difference in risks of dying from kidney disease, stroke, and CVD but not cancer. When examining types of cancer deaths, black participants died at higher rates from multiple myeloma, pancreatic cancer, and prostate cancer, which baseline risk factors did not explain either., Conclusion: Factors contributing to poorer physical and cognitive performance in similarly aged black men and women could be targets to reduce excess mortality from CVD, stroke, and kidney disease. More work is needed to identify factors contributing to cancer mortality disparities., (© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society.)

Background: Bleeding is the major risk of aspirin treatment, especially in the elderly. A consensus definition for clinically significant bleeding (CSB) in aspirin primary prevention trials is lacking in the literature., Methods: This paper details the development, modification, application, and quality control of a definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a primary prevention trial of aspirin in 19,114 community-dwelling elderly men and women. In ASPREE a confirmed bleeding event needed to meet criteria both for substantiated bleeding and clinical significance. Substantiated bleeding was defined as: 1) observed bleeding, 2) a reasonable report of symptoms of bleeding, 3) medical, nursing or paramedical report, or 4) imaging evidence. Bleeding was defined as clinically significant if it: 1) required transfusion of red blood cells, 2) required admission to the hospital for >24 h, or prolonged a hospitalization, with bleeding as the principal reason, 3) required surgery to stop the bleeding, or 4) resulted in death. Bleeding sites were subclassified as upper gastrointestinal, lower gastrointestinal, intracranial (hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, extradural hematoma, or other), or other sites. Potential events were retrieved from medical records, self-report or notification from treating doctors. Two reviewers adjudicated each event using electronic adjudication software, and discordant cases were reviewed by a third reviewer. Adjudication rules evolved to become more strictly defined as the trial progressed and decision rules were added to assist with frequent scenarios such as post-operative bleeding., Conclusions: This paper provides a detailed methodologic description of the development of a standardized definition for clinically significant bleeding and provides a benchmark for development of a consensus definition for future aspirin primary prevention trials., Trial Registration: ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and on clinicaltrials.gov (NCT01038583).

Objectives: This study sought to determine whether Holter-based parameters of heart rate variability (HRV) are independently associated with incident heart failure among older adults in the CHS (Cardiovascular Health Study) as evidenced by an improvement in the predictive power of the Health Aging and Body Composition Heart Failure (Health ABC) score., Background: Abnormal HRV, a marker of autonomic dysfunction, has been associated with multiple adverse cardiovascular outcomes but not the development of congestive heart failure (CHF)., Methods: Asymptomatic CHS participants with interpretable 24-h baseline Holter recordings were included (n = 1,401). HRV measures and premature ventricular contraction (PVC) counts were compared between participants with (n = 260) and without (n = 1,141) incident CHF on follow-up. Significantly different parameters between groups were added to the components of the Health ABC score, a validated CHF prediction tool, using stepwise Cox regression., Results: The final model included components of the Health ABC score, In PVC counts (adjusted hazard ratio [aHR]: 1.12; 95% confidence interval [CI]: 1.07 to 1.19; p < 0.001) and the following HRV measures: abnormal heart rate turbulence onset (aHR: 1.52; 95% CI: 1.11 to 2.08; p = 0.009), short-term fractal scaling exponent (aHR: 0.27; 95% CI: 0.14 to 0.53; p < 0.001), in very low frequency power (aHR: 1.28; 95% CI: 1.02 to 1.60; p = 0.037), and coefficient of variance of N-N intervals (aHR: 0.94; 95% CI: 0.90 to 0.99; p = 0.009). The C-statistic for the final model was significantly improved over the Health ABC model alone (0.77 vs. 0.73; p = 0.0002)., Conclusions: Abnormal HRV parameters were significantly and independently associated with incident CHF in asymptomatic, older adults. When combined with increased PVCs, HRV improved the predictive power of the Health ABC score., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We aimed to investigate if trajectory components (baseline level, slope, and variability) of peripheral interleukin-6 (IL-6) over time were related to cognitive impairment and smaller hippocampal volume and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus and with cognitive impairment among 135 older adults (70-79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (odds ratio [OR] = 5.86, 95% confidence interval [CI]: 1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (β = -0.008, standard error = 0.004, p = 0.03). After adjustment for hippocampal volume, the OR of cognitive impairment decreased for each unit of IL-6 variability and CIs widened (OR = 4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Severe infections, often requiring ICU admission, have been associated with persistent cognitive dysfunction. Less severe infections are more common and whether they are associated with an increased risk of dementia is unclear. We determined the association of pneumonia hospitalization with risk of dementia in well-functioning older adults., Design: Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia., Setting: Five academic medical centers in the United States., Subjects: Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years., Interventions: None., Measurement and Main Results: We identified pneumonia hospitalizations using International Classification of Diseases, 9th Edition-Coding Manual codes and validated them in a subset. Less than 3% of pneumonia cases necessitated ICU admission, mechanical ventilation, or vasopressor support. Dementia was adjudicated based on neuropsychological evaluation, neurological examination, and MRI. Two hundred twenty-one participants (7.2%) incurred at least one hospitalization with pneumonia (mean time to pneumonia = 3.5 yr). Of these, dementia was developed in 38 (17%) after pneumonia, with half of these cases occurring 2 years after the pneumonia hospitalization. Hospitalization with pneumonia was associated with increased risk of time to dementia diagnosis (unadjusted hazard ratio = 2.3; CI, 1.6-3.2; p < 0.0001). The association remained significant when adjusted for age, sex, race, study site, education, and baseline mini-mental status examination (hazard ratio = 1.9; CI, 1.4-2.8; p < 0.0001). Results were unchanged when additionally adjusted for smoking, hypertension, diabetes, heart disease, and preinfection functional status. Results were similar using propensity analysis where participants with pneumonia were matched to those without pneumonia based on age, probability of developing pneumonia, and similar trajectories of cognitive and physical function prior to pneumonia (adjusted prevalence rates, 91.7 vs 65 cases per 1,000 person-years; adjusted prevalence rate ratio = 1.6; CI, 1.06-2.7; p = 0.03). Sensitivity analyses showed that the higher risk also occurred among those hospitalized with other infections., Conclusion: Hospitalization with pneumonia is associated with increased risk of dementia.

Objective: To determine whether a high prevalence (55%) of Aβ deposition in a cohort of individuals remaining dementia-free into their 9th and 10th decades is associated with cognitive decline prior to imaging., Methods: A total of 194 participants (mean age 85.5 years, range 82-95) who completed the Ginkgo Evaluation of Memory Study (GEMS) and remained dementia-free subsequently completed Pittsburgh compound B-PET imaging. We examined cross-sectional associations between Aβ status and performance on a broad neuropsychological test battery completed at GEMS entry 7-9 years prior to neuroimaging. We also longitudinally examined cognition over annual evaluations using linear mixed models., Results: At GEMS screening (2000-2002), participants who were Aβ-positive in 2009 had lower performance on the Stroop test (p < 0.01) and Raven's Progressive Matrices (p = 0.05), with trend level difference for Block Design (p = 0.07). Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail-Making Test parts A and B, indicating greater performance decline prior to neuroimaging for Aβ-positive relative to Aβ-negative participants (ps < 0.05)., Conclusions: Highly prevalent Aβ deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency, and psychomotor speed beginning 7-9 years prior to neuroimaging. Mean differences in nonmemory domains, primarily executive functions, between Aβ-status groups may be detectable 7-9 years before neuroimaging.

Background: Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined., Methods: We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176)., Results: Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p = .55), as compared with smaller changes for both., Conclusion: Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

Exceptional aging has been defined as maintenance of physical and cognitive function beyond the median lifespan despite a history of diseases and/or concurrent subclinical conditions. Since immunity is vital to individual fitness, we examined immunologic fingerprint(s) of highly functional elders. Therefore, survivors of the Cardiovascular Health Study in Pittsburgh, Pennsylvania, USA were recruited (n = 140; mean age = 86 years) and underwent performance testing. Blood samples were collected and examined blindly for humoral factors and T cell phenotypes. Based on results of physical and cognitive performance testing, elders were classified as "impaired" or "unimpaired", accuracy of group assignment was verified by discriminant function analysis. The two groups showed distinct immune profiles as determined by factor analysis. The dominant immune signature of impaired elders consisted of interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor-α, and T cells expressing inhibitory natural killer-related receptors (NKR) CD158a, CD158e, and NKG2A. In contrast, the dominant signature of unimpaired elders consisted of IL-5, IL-12p70, and IL-13 with co-expression of IFN-γ, IL-4, and IL-17, and T cells expressing stimulatory NKRs CD56, CD16, and NKG2D. In logistic regression models, unimpaired phenotype was predicted independently by IL-5 and by CD4(+)CD28(null)CD56(+)CD57(+) T cells. All elders had high antibody titers to common viruses including cytomegalovirus. In cellular bioassays, T cell receptor (TCR)-independent ligation of either CD56 or NKG2D elicited activation of T cells. Collectively, these data demonstrate the importance of immunological parameters in distinguishing between health phenotypes of older adults. NKR(+) T cells and cytokine upregulation indicate a unique physiologic environment in old age. Correlation of particular NKR(+) T cell subsets and IL-5 with unimpaired performance, and NKR-driven TCR-independent activation of T cells suggest novel immunopathway(s) that could be exploited to improve immunity in old age.

Objectives: To describe retention according to age and visit type (clinic, home, telephone) and to determine characteristics associated with visit types for a longitudinal epidemiological study in older adults., Design: Longitudinal cohort study., Setting: Four U.S. clinical sites., Participants: Five thousand eight hundred eighty-eight Cardiovascular Health Study (CHS) participants aged 65 to 100 at 1989/90 or 1992/93 enrollment (58.6% female; 15.7% black). CHS participants were contacted every 6 months, with annual assessments through 1999 and in 2005/06 for the All Stars Study visit of the CHS cohort (aged 77-102; 66.5% female; 16.6% black)., Measurements: All annual contacts through 1999 (n=43,772) and for the 2005/06 visit (n=1,942)., Results: CHS had 43,772 total participant contacts from 1989 to 1999: 34,582 clinic visits (79.0%), 2,238 refusals (5.1%), 4,401 telephone visits (10.1%), 1,811 home visits (4.1%), and 740 other types (1.7%). In 2005/06, the All Stars participants of the CHS cohort had 36.6% clinic, 22.3% home, and 41.1% telephone visits. Compared with participants aged 65 to 69, odds ratios of not attending a CHS clinic visit were 1.82 (95% confidence interval (CI)=1.54-2.13), 2.94 (95% CI=2.45-3.57), 4.55 (95% CI=3.70-5.56), and 9.09 (95% CI=7.69-11.11) for those aged 70 to 74, 75 to 79, 80 to 84, and 85 and older, respectively, in sex-adjusted regression. In multivariable regression, participants with a 2005/06 clinic visit were younger, more likely to be male and in good health, and had had better cognitive and physical function 7 years earlier than participants with other visit types. Participants with home, telephone, and missing visits were similar on characteristics measured 7 years earlier., Conclusion: Offering home, telephone, and proxy visits are essential to optimizing follow-up of aging cohorts. Home visits increased in-person retention from 36.5% to 58.8% and diversified the cohort with respect to age, health, and physical functioning.

Background: Cardiovascular disease (CVD) was a preplanned secondary outcome of the Ginkgo Evaluation of Memory Study. The trial previously reported that Ginkgo biloba had no effect on the primary outcome, incident dementia., Methods and Results: The double-blind trial randomly assigned 3069 participants over 75 years of age to 120 mg of G biloba EGb 761 twice daily or placebo. Mean follow-up was 6.1 years. The identification and classification of CVD was based on methods used in the Cardiovascular Health Study. Differences in time to event between G biloba and placebo were evaluated using Cox proportional hazards regression adjusted for age and sex. There were 355 deaths in the study, 87 due to coronary heart disease with no differences between G biloba and placebo. There were no differences in incident myocardial infarction (n=164), angina pectoris (n=207), or stroke (151) between G biloba and placebo. There were 24 hemorrhagic strokes, 16 on G biloba and 8 on placebo (not significant). There were only 35 peripheral vascular disease events, 12 (0.8%) on G biloba and 23 (1.5%) on placebo (P=0.04, exact test). Most of the peripheral vascular disease cases had either vascular surgery or amputation., Conclusions: There was no evidence that G biloba reduced total or CVD mortality or CVD events. There were more peripheral vascular disease events in the placebo arm. G biloba cannot be recommended for preventing CVD. Further clinical trials of peripheral vascular disease outcomes might be indicated., Clinical Trial Registration: clinicaltrials.gov Identifier: NCT00010803.

Objectives: To identify, characterize and compare the frequency of mild cognitive impairment (MCI) subtypes at baseline in a large, late-life cohort (n = 3063) recruited into a dementia prevention trial., Method: A retrospective, data-algorithmic approach was used to classify participants as cognitively normal or MCI with corresponding subtype (e.g. amnestic vs. non-amnestic, single domain vs. multiple domain) based on a comprehensive battery of neuropsychological test scores, with and without Clinical Dementia Rating (CDR) global score included in the algorithm., Results: Overall, 15.7% of cases (n = 480) were classified as MCI. Amnestic MCI was characterized as unilateral memory impairment (i.e. only verbal or only visual memory impaired) or bilateral memory impairment (i.e. both verbal and visual memory impaired). All forms of amnestic MCI were almost twice as frequent as non-amnestic MCI (10.0% vs. 5.7%). Removing the CDR = 0.5 ('questionable dementia') criterion resulted in a near doubling of the overall MCI frequency to 28.1%., Conclusion: Combining CDR and cognitive test data to classify participants as MCI resulted in overall MCI and amnestic MCI frequencies consistent with other large community-based studies, most of which relied on the 'gold standard' of individual case review and diagnostic consensus. The present data-driven approach may prove to be an effective alternative for use in future large-scale dementia prevention trials.

Objectives: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS)., Design: Observational., Setting: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh)., Participants: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004., Measurements: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only., Results: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% confidence interval (CI)=0.89-0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95% CI=0.58-0.64; stroke, kappa=0.59, 95% CI=0.54-0.64; chronic obstructive pulmonary disease, kappa=0.58, 95% CI=0.51-0.65; dementia, kappa=0.40, 95% CI=0.34-0.45; and pneumonia, kappa=0.35, 95% CI=0.29-0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5%) to dementia as the underlying cause., Conclusion: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

Background: Bariatric surgery has emerged as the most effective treatment for class III obesity (body mass index, >or=40). The number of operations continues to increase. We measured case fatality and death rates by time since operation, sex, age, specific causes of death, and mortality rates., Design and Setting: Data on all bariatric operations performed on Pennsylvania residents between January 1, 1995, and December 31, 2004, were obtained from the Pennsylvania Health Care Cost and Containment Council. Matching mortality data were obtained from the Division of Vital Records, Pennsylvania State Department of Health., Outcome Measures: Age- and sex-specific death rates after bariatric surgery., Results: There were 440 deaths after 16 683 operations (2.6%). Age-specific death rates were much higher in men than in women and increased with age. Age- and sex-specific death rates after bariatric surgery were substantially higher than comparable rates for the age- and sex-matched Pennsylvania population. The 1-year case fatality rate was approximately 1% and nearly 6% at 5 years. Less than 1% of deaths occurred within the first 30 days. Fatality increased substantially with age (especially among those > 65 years), with little evidence of change over time. Coronary heart disease was the leading cause of death overall, being cited as the cause of death in 76 patients (19.2%). Therapeutic complications accounted for 38 of 150 natural deaths within the first 30 days, including pulmonary embolism in 31 (20.7%), coronary heart disease in 26 (17.3%), and sepsis in 17 (11.3%)., Conclusions: There was a substantial excess of deaths owing to suicide and coronary heart disease. Careful monitoring of bariatric surgical procedures and more intense follow-up could likely reduce the long-term case fatality rate in this patient population.

The epidemic of late life dementia, prominence of use of alternative medications and supplements, and initiation of efforts to determine how to prevent dementia have led to efforts to conduct studies aimed at prevention of dementia. The GEM (Ginkgo Evaluation of Memory) study was initially designed as a 5-year, randomized double-blind, placebo-controlled trial of Ginkgo biloba, administered in a dose of 120 mg twice per day as EGb761, in the prevention of dementia (and especially Alzheimer's disease) in normal elderly or those with mild cognitive impairment. The study anticipates 8.5 years of participant follow-up. Initial power calculations based on estimates of incidence rates of dementia in the target population (age 75+) led to a 3000-person study, which was successfully recruited at four clinical sites around the United States from September 2000 to June 2002. Primary outcome is incidence of all-cause dementia; secondary outcomes include rate of cognitive and functional decline, the incidence of cardiovascular and cerebrovascular events, and mortality. Following screening to exclude participants with incident dementia at baseline, an extensive neuropsychological assessment was performed and participants were randomly assigned to treatment groups. All participants are required to have a proxy who agreed to provide an independent assessment of the functional and cognitive abilities of the participant. Assessments are repeated every 6 months. Significant decline at any visit, defined by specific changes in cognitive screening scores, leads to a repeat detailed neuropsychological battery, neurological and medical evaluation and MRI scan of the brain. The final diagnosis of dementia is achieved by a consensus panel of experts. Side effects and adverse events are tracked by computer at the central data coordinating center and unblinded data are reviewed by an independent safety monitoring board. Studies such as these are necessary for this and a variety of other potential protective agents to evaluate their effectiveness in preventing or slowing the emergence of dementia in the elderly population.

Objectives: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries., Methods: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study., Results: The questionnaires were completed by 4889 (91.1%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor's lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors., Conclusions: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.

Objectives: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort., Design: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia., Setting: Four U.S. communities., Participants: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years., Measurements: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD., Results: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%)., Conclusion: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.

Background: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals., Objective: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors., Methods: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality., Results: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46)., Conclusions: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

OBJECTIVE: Analyze clinical, accepted biochemical, physiologic, and socioeconomic risk factors and correlate them with hospital utilization in an elderly population. DESIGN: Prospective, observational study in a defined, randomly recruited population. PARTICIPANTS: 5201 Medicare participants enrolled in the Cardiovascular Health Study (CHS). METHODS: Medicare recipients were randomly assigned to participate in an observational study. Baseline data were compared to hospital admissions and days of hospitalization over four years. DATA ANALYSIS: Data were grouped by type of risk factor and analyzed by Tobit analysis and logistic regression. RESULTS: Baseline variables associated with hospital use (p is less than 0.0001) were history of CHF, stroke, angina, hypertension, ln (timed walk), ln (blocks walked/week), age, gender, and clinic site. Factors not entering the model (p is greater than 0.05) were income, education, smoking, diabetes, weight, dietary fat, marital status, depression, and measures of mental function. CONCLUSIONS: In the elderly, existing health status is the major determinant of hospitalization and overwhelms many classic "risk factors" for morbidity.

Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Objective: This article evaluates a demonstration program that extended coverage for disease prevention/health promotion services to Medicare beneficiaries., Study Setting/data Sources: Community-dwelling Medicare beneficiaries who lived in five rural counties in northwest Pennsylvania were recruited between May and December 1989. The demonstration lasted 18 months and beneficiaries were followed for an additional 18 months. Data for the evaluation came from an initial health risk assessment, Medicare administrative records, follow-up surveys, and redeemed vouchers for the waivered services. The waivered services included health screenings, influenza immunization, nutritional counseling, smoking and alcohol cessation, and depression/dementia evaluations., Study Design: Medicare beneficiaries were randomized to one of two experimental groups and a control group. One experimental group received the newly waived services from hospitals that received a capitated fee; the other received services from providers who were paid fee-for-service. Eligibility for most waivered services was based on risk. Chi-square tests of association were used to determine if use of health promotion services and use of medical care services varied across groups. Logistic regressions were used to assess the factors associated with participation. Product-limit survival analysis was used to assess whether mortality rates varied across groups., Principal Findings: Participation rates in the new programs varied by program and by experimental group, and ranged from 16.8 percent for smoking cessation programs to 58 percent for influenza immunization. The demonstration led to an increase in influenza immunization rates relative to the control group. There were no differences in the use of medical care services or health outcomes between the experimental and control groups., Conclusions: Older rural Americans will modestly increase their use of disease prevention/ health promotion services if they are covered by Medicare. Use will be higher among those with more education. Further research is needed to assess long-term benefits of such programs.

Deaths among 35- to 44-year-old black and white men and women residing in Allegheny County, Pennsylvania, were investigated. All coroner-certified nontraumatic deaths and practitioner-certified deaths coded as heart, cerbrovascular, or arterial disease, diabetes mellitus, and sudden or ill-defined causes were studied. Using autopsy, coroner, hospital, physician, and/or informant information about medical history, characteristics, and circumstances of death, physicians validated the deaths as due to coronary heart disease (CHD) or another cause. In 1984 to 1989, 616 deaths were investigated, 384 of which were sudden (within 24 hours of onset). Overall CHD mortality was 35.4/100,000/y for white males, 8.4/100,000/y for white females, 61.3/100,000/y for black males, and 19.5/100,000/y for black females. Although rates varied widely, characteristics, circumstances, and disease history were similar across race-sex groups. CHD mortality was 73% higher in black than white males. Approximately 80% of CHD deaths were sudden.

Objective: To investigate the prevalence and characteristics of nocturnal enuresis in community-dwelling older adults and to identify potential predisposing variables., Design: Interview survey., Setting: Five rural counties in northwestern Pennsylvania., Participants: Subjects were 3884 community-dwelling older adults aged 65 to 79 years who volunteered for a health promotion demonstration., Measurements: The dependent variable was self-reported accidental loss of urine during sleep. Independent variables included demographic variables, self-reported disease history and symptomatology, and standardized screening instruments for depression (CES-D), dementia (MMSE), and functional status (ADLs)., Main Results: Prevalence of nocturnal enuresis was 2.1%, and was significantly higher among women (2.9%) compared with men (1.0%; P < .0001). Compared with subjects with daytime incontinence only, those with nocturnal enuresis reported greater severity and impact of incontinence on several parameters. Enuretics were more likely to have received treatment; treatment outcome, however, was significantly less successful. In univariate analyses, enuresis was significantly associated with symptoms of congestive heart failure (CHF), impairment in activities of daily living, depression, and use of sleep medications at least once per week. In stepwise logistic regression modeling, two symptoms of congestive heart failure and regular use of sleep medication entered the model., Conclusions: Nocturnal enuresis appears to be uncommon among older adults, but it may be associated with poorer therapeutic outcomes compared with the more common forms of daytime incontinence. The findings are consistent with the hypothesis that daytime fluid accumulation followed at night by mobilization of excess fluid is a contributor to enuresis in older adults.

Trends in coronary heart disease mortality and sudden death were studied in 35- to 44-year-old white male residents of Allegheny County, Pennsylvania. Deaths coded as any cardiac or vascular disease, diabetes, unexplained sudden death, and other rubrics were eligible for investigation, and the cause of death was validated by physicians examining multiple data sources about the deaths. During 1970-1990, 1,424 white male deaths were investigated, with 903 validated as coronary heart disease. In that time span, white male coronary heart disease mortality fell from 93.4 to 36.7 per 100,000 population per year, a 60% decline. Little proportionate change was seen in characteristics of the deaths, which were predominantly sudden and out-of-hospital. Diabetes mellitus history increased proportionately over time, largely because diabetics' mortality rates, unlike those of all other subgroups, did not fall. These observations support the contention that the decline in coronary heart disease mortality relates to risk factor modification more than to improvements in the treatment of coronary heart disease. Differences in death certification practices must be considered when interpreting and comparing vital statistics data.

While previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.

The Health Care Financing Administration (HCFA) funded a series of demonstration programs to learn about the implications of extending coverage for disease prevention/health promotion services to Medicare beneficiaries. This article examines the use of such services by a rural population under this demonstration program. Individuals enrolled in the demonstration were eligible for specific risk reduction interventions. They were enrolled in one of two groups: (1) a hospital-based group in which hospitals were paid a capitated fee for providing all services and (2) a physician-based group in which physicians were paid fee-for-service for providing each service. Chi-square tests of association as well as logistic regression models were used to assess whether eligibility for services, and use of services by those eligible, varied by group and by sociodemographic characteristics. Forty-one percent were eligible for a nutrition program, 11% for smoking cessation, 2% for alcohol counseling, and 7% for dementia/depression evaluations. Participation in the programs varied across the programs and within programs by gender, education, and group assignment. Older rural Americans will use some disease prevention/health promotion services if they are covered by Medicare. Use will be higher among those with more education. Rural beneficiaries are more likely to use preventive services if encouraged to do so by their doctors rather than by hospital-based programs.

Some epidemiologic studies have compared the characteristics of individuals who participate, refuse, and are unreachable in population studies, but results have been inconsistent. The Rural Health Promotion Project attempted to recruit all Medicare Part B noninstitutionalized individuals age 65-79 years in a rural community for a trial of preventive health services. Of 962 potential subjects, 360 (37.4%) participated, 253 (26.3%) refused, 176 (18.3%) were ineligible, and 152 (15.8%) were never reached by phone or mail. Approximately 3 years later, we reinterviewed the participants, refusals, and as many of the unreachables as possible. The 3-year mortality was similar for both refusals and participants (approximately 9%) but was much higher for ineligibles (29.0%) and unreachables (23.7%). Participants were more likely to have disease history, to have behavioral risk factors for disease, and to use health screening services. Refusals were the healthiest and possibly chose not to participate because they did not have risk factors targeted by the program. The unreachables had the highest prevalence of disability and health care inpatient reimbursement and may have been ineligible for the demonstration had they volunteered. We conclude that failure to reach potential participants for health promotion services may be a warning of "high risk."

Background: Influenza is responsible for significant morbidity, mortality, and medical costs, but immunization rates in the elderly remain low., Methods: As part of a demonstration project in rural Pennsylvania, 1,989 community-dwelling Medicare beneficiaries, 65-79 years old, completed a health risk appraisal including questions about flu shots. Participants were randomized to two experimental (hospital or physician) or control groups. Experimental groups were offered free flu shots for the 1990-91 flu season. Follow-up interviews to determine vaccination rates were completed about 1 year later., Results: Baseline immunization rates were almost identical for the hospital-based (41.2%), physician-based (41.3%), and control group not offered free immunizations (40.6%). Follow-up rates for the groups offered immunizations rose significantly to 63.6 and 69.1% for hospital and physician groups, respectively, while the control group also increased significantly to 54.1%. Individuals who were more educated, were older, and had greater chronic diseases history (myocardial infarction, hypertension, and pulmonary disease) were more likely to be immunized. Male and married elderly were more likely to be immunized as a result of the demonstration., Conclusions: Increasing community education and providing immunizations free through Medicare will increase immunization rates among elderly. The elderly are more likely to receive flu shots provided through physicians' offices than through hospital-based clinics.

Objective: To examine treatment seeking for urinary incontinence among older adults and to identify characteristics associated with treatment-seeking behavior., Design: Survey., Setting: Five rural counties in northwestern Pennsylvania., Participants: 1104 community-dwelling ambulatory older adults aged 65 to 79 years with self-reported urinary incontinence. Participants were a subgroup of a large sample (n = 3884) who volunteered for a study of health promotion services. Those who reported urinary incontinence within the past year, during an in-person health risk appraisal, were included in this analysis., Measurements: Reporting incontinence to the participant's physician was the main dependent measure., Main Results: 37.6% of the participants had told their physician about loss of urine. Reporting incontinence to a physician was strongly associated with severity of incontinence as indicated by eight measures (P < 0.001). Treatment seeking was also related to type of incontinence (P < 0.001), physical disability (P < 0.01), and the pattern of health care utilization (P < 0.01). In multiple logistic regression analyses, younger age, physical disability, and frequency of physical and rectal examinations had significant predictive value independent of severity. Not associated with treatment seeking were gender, marital status, income, employment status, educational level, and distance from health care provider., Conclusions: The majority of older adults with urinary incontinence do not report the condition to their doctor. Severity of incontinence, physical disability, and a pattern of regular health care utilization appear to be the strongest predictors of treatment-seeking behavior.

Few studies have evaluated the efficacy of cholesterol-lowering interventions in a community setting and have included a control or comparison group. As part of a preventive health demonstration project in rural Pennsylvania, Medicare beneficiaries underwent cholesterol screening to identify high-risk individuals with serum cholesterol levels > or = 240 mg/dL. These high-risk individuals were randomized to a cholesterol-lowering intervention through either local hospitals or physicians' offices or to a control group. Baseline and follow-up serum cholesterol levels collected two to three years later were compared according to service location (hospital versus physician's office), intervention attendance, degree of participation, baseline heart disease history, and cholesterol-lowering medication use at follow-up. Serum cholesterol levels decreased between 5.7% and 6.6% in the hospital-based and physician-based groups, as well as in a control group not offered the intervention. Participation rates did not differ between treatment groups, nor did participation affect serum cholesterol levels. Attendance level and heart disease history were not associated with a greater decrease in serum cholesterol levels. Individuals reporting cholesterol-lowering drug use at follow-up had significantly higher baseline serum cholesterol levels and a significantly greater decrease in total serum cholesterol (P < .0001) than those not on medication. Both nonpharmacological (diet) and pharmacological (drug) interventions will reduce serum cholesterol levels and heart attack risk. The study results suggest that, at least for older individuals, the impact of nonpharmacological interventions on the community is minimal. We conclude that only very aggressive treatment will significantly loser serum cholesterol levels in older individuals at risk for heart attack.

Background: Low serum cholesterol has been associated with morbidity and mortality in the elderly. This study compared the health, functional status, and two-year mortality rates of community-dwelling rural elderly with serum cholesterol < 150 mg/dl to age- and sex-matched controls with serum cholesterol 200-240 mg/dl., Methods: Self-reported disease history, disability, health habits, and cognitive function data were collected at a health risk appraisal interview. A single blood sample was also collected and analyzed for total serum cholesterol at a central lab., Results: Of the 3,874 participants, 109 (2.8%) had total cholesterol levels < 150 mg/dl. Seventy-five percent of the low cholesterol group were male compared to 44% in the main study population. The low cholesterol group had significantly greater smoking history, current cigarettes smoked, diabetes history, angina and COPD symptoms, and assistance needed for heavy and light work. Men in the low cholesterol group had significantly lower blood pressure. After two years, 14 (12.8%) of the low cholesterol group had died vs 16 (7.3%) in the control group. There was no relationship to specific causes of death and cholesterol level., Conclusion: A very low cholesterol level in older individuals should be evaluated carefully to determine whether it is due to genetic or life-style factors such as diet or, more likely, is a marker of disease.

Background: Although interest in health promotion for the elderly is increasing, the issues of recruitment into such programs and self-selection have not been well explored. While clinical studies require high participation levels and expensive recruitment, community efforts are satisfied with recruiting small numbers of volunteers from poorly defined populations. These small samples may not be representative of the populations at risk., Methods: As part of the Rural Health Promotion Project, a Medicare demonstration, community-based recruitment methods were evaluated and participant characteristics were compared. A total of 3,884 individuals ages 65-79 were recruited in northwestern Pennsylvania, using four sequential recruitment strategies, varying in aggressiveness. The methods were: (A) mail only, (B) mail with phone recruitment follow-up, (C) mail with phone recruitment and scheduling, and (D) mail with aggressive phone recruitment and scheduling., Results: Recruitment yields were Method A, 13.5%; B, 21.1%; and C, 31.6%. The most aggressive Method (D) yielded 37.0% participation. More aggressive methods (C and D) recruited more educated individuals. No other demographic or health status differences were noted., Conclusion: These data show that large numbers of the elderly can be recruited into a health promotion program using aggressive methods and professional interviewers.

Trends in coronary heart disease (CHD) mortality were examined among 35-44-year-old white men during 1970-1986. Death certificates were obtained for 1,216 cases. All were coroner-certified natural deaths and noncoroner-certified deaths due to vascular diseases and diabetes mellitus. Autopsy data, coroner's reports, hospital records, physician's reports, and informants were used to validate diagnoses. The reviewers rejected 73 of 805 CHD certifications, but they validated 54 cases not certified as CHD on the death certificate as CHD. The CHD mortality rate fell from 90.6/100,000/year in 1970-1972 to 40.3/100,000/year in 1985-1986. Approximately two thirds of the decline was related to a decline in sudden deaths including 41.6% due to incident sudden CHD death. The proportion of diabetics among validated CHD deaths rose dramatically from 6.5% in 1970-1972 to 23.0% in 1985-1986. The CHD mortality rate among diabetics apparently did not decline during the 17 years of the study. We conclude that primary prevention has contributed substantially to the CHD decline in the 35-44-year age group. Better diagnoses and treatment, especially of angina pectoris and of patients after a myocardial infarction, may also have been important. Control of CHD in diabetics must take high priority in further prevention strategies.