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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.

Background Intensive systolic blood pressure treatment ( 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 ( 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.

Background Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied. Methods We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF. Results A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF. Conclusions Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.

Introduction: Intensive systolic blood pressure (SBP) treatment ( Methods: We projected life expectancy after SPRINT using six US cohort studies in the National Heart, Lung, and Blood Institute Pooled Cohorts Study (NHLBI-PCS). We included SPRINT-eligible NHLBI-PCS participants as those aged >=50 years with SBP 130-180 mm Hg and increased cardiovascular disease (CVD) risk without diabetes or history of stroke. We used propensity scores to weight NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (=4 years) using an age-based FPSM and applied the formula to SPRINT participants to predict post-trial survival. We combined in- and post-trial survival to project overall life expectancy for each SPRINT participant and compared it to commonly used Gompertz methods. Results: We included 8,584 SPRINT and 10,610 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.7 (8.8) years, 35.5% and 38.3% were female in SPRINT and NHLBI-PCS, respectively. Predicted in-trial survival was similar to that observed in SPRINT with both FPSM and Gompertz models (Figure). Assuming constant treatment effects, projected mean life expectancy using the NHLBI-PCS method was 21.1 (7.4) years with intensive and 19.3 (7.2) years with standard treatment; compared to 11.2 (2.3) and 10.5 (2.2) years, respectively, using the Gompertz method. Conclusions: Combining SPRINT and NHLBI-PCS observed data may offer a more realistic estimate of life expectancy than by parametrically extrapolating SPRINT data.

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.)

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). Keywords: Aspirin, Primary prevention, Methods, Hemorrhage, Bleeding

OBJECTIVE: We assessed mobility disability trajectories before death in a large sample of very old adults using two analytic approaches to determine how well they correspond. DESIGN: Decedent sample from the Health, Aging and Body Composition Study (Health ABC). Data were collected between 1997 and 2015. SETTING: A population-based sample of 3075 participants, randomly selected from well-functioning White Medicare beneficiaries and all African American community residents meeting age criteria (70–79 years) in Pittsburgh, PA, and Memphis, TN. PARTICIPANTS: Of the 1991 participants who died by the end of the study, 1410 were interviewed for three years prior to death, including an interview six months before dying. EXPOSURES: Participants were interviewed in person or by phone at least every six months throughout the study. MEASUREMENTS: We analyzed self-reported mobility collected prospectively at six month intervals during the last three years of life. We derived trajectories in two ways: first by averaging decline within decedent groups pre-specified by clinical conditions and, second, by estimating trajectory models using maximum-likelihood semiparametric modeling. RESULTS: Classification by clinical conditions (sudden death, terminal, organ failure and frailty) accounted for 98% of decedents and produced groups with different characteristics. Five disability trajectories were identified: late decline, progressive disability, moderate disability, early decline, and persistent disability. Disability trajectory and clinical condition grouping both confirmed previous research but were only marginally related. CONCLUSIONS: Derived disability trajectories and grouping by clinical conditions both provide useful information about different facets of the end-of-life experience. The lack of fit between them suggests a need for greater attention to heterogeneity in disability in the period before death.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

Background Heart rate variability ( HRV ) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24‐hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score ( CHS ‐ SCORE ), previously developed at the baseline examination. Methods and Results N=884 stroke‐free CHS participants (age 75.3±4.6), with 24‐hour Holters adequate for HRV analysis at the 1994–1995 examination, had 68 strokes over ≤8 year follow‐up (median 7.3 [interquartile range 7.1–7.6] years). The value of adding HRV to the CHS ‐ SCORE was assessed with stepwise Cox regression analysis. The CHS ‐ SCORE predicted incident stroke ( HR =1.06 per unit increment, P =0.005). Two HRV parameters, decreased coefficient of variance of NN intervals ( CV %, P =0.031) and decreased power law slope ( SLOPE , P =0.033) also entered the model, but these did not significantly improve the c‐statistic ( P =0.47). In a secondary analysis, dichotomization of CV % ( LOWCV % ≤12.8%) was found to maximally stratify higher‐risk participants after adjustment for CHS ‐ SCORE . Similarly, dichotomizing SLOPE ( LOWSLOPE HRV categories were combined (eg, HIGHCV % with HIGHSLOPE ), the c‐statistic for the model with the CHS ‐ SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS ‐ SCORE alone ( P =0.02). Conclusions In this sample of older adults, 2 HRV parameters, CV % and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8‐year follow‐up. These findings will require validation in separate, larger cohorts.

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.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.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.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.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.

Background: Our recent research suggests that a fluctuating trajectory, previously thought to be the experience of those dying with heart failure or chronic lung disease, may not accurately characterize the end of life for these patients. Objective: We sought to further examine health and function to investigate whether other measures or a different time frame captures the purported exacerbation/recovery trajectory associated with these diseases. Design: Function and health data were collected prospectively at six-month intervals for 17 years during the Heath, Aging and Body Composition Study. Subjects and Measures: We analyzed self-reported mobility, health status, and health care utilization for 1410 decedents, defining high fluctuations as transitions in two or more adjacent assessment pairs during the last three years of life. Results: Among decedents, only 207 (14.7%) reported two or more changes in mobility during the last three years of life; and 586 (41.6%) reported more than two transitions in self-reported health during the period. This fluctuation was not associated with any clinical condition in the three years before death, but decedents with chronic heart failure or chronic lung disease reported significantly more changes in mobility (odds ratio = 1.15, p = 0.025) for a longer follow-up period. Decedents with heart failure were also more likely to report hospital stays in the last three years of life. Conclusions: Fluctuations in mobility and self-reported health do not differ by clinical condition in the three years before death, but people dying with chronic heart failure or chronic lung disease are more frequently hospitalized during this period and experience more unstable mobility for a longer period of observation.

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: U.S. black individuals die at higher rates than white individuals. To inform points of intervention to reduce excess mortality, we sought to understand which causes of death were higher among black versus white community-dwelling older adults and determine whether differences in baseline risk factors explained racial differences in mortality. DESIGN: Longitudinal cohort study. SETTING: Pittsburgh, Pennsylvania and Memphis, Tennessee. PARTICIPANTS: The Health, Aging, and Body Composition study followed N=3075 black and white men and women aged 70–79 during recruitment (1997/98; 48% men, 42% black) for a median of 13 years. MEASUREMENTS: Cause of death was adjudicated by a committee of physicians and categorized as: cardiovascular disease, stroke, cancer, dementia, pulmonary, infection, kidney, or ‘other’ causes. Using competing risks regression, we examined whether known risk factors at baseline (demographics, smoking, body mass index, chronic diseases, physical function, and cognition) could explain racial differences in cause-specific mortality risk. RESULTS: During follow-up, 1991 (65%) participants died. Black participants died at higher rates from cancer, kidney disease, stroke, and cardiovascular disease (hazard ratio (95% confidence interval): 1.36 (1.14, 1.63); 2.09 (1.16, 3.74); 1.31 (0.98, 1.76); 1.16 (0.98, 1.37), respectively). The racial difference in risks of dying from kidney disease, stroke, and cardiovascular disease was explained most by worse physical and cognitive performance at baseline among black participants. However, the racial difference in cancer mortality was not explained by differences in baseline risk factors. When examining types of cancer deaths, black participants died at higher rates from multiple myeloma, pancreatic cancer, and prostate cancer, which were also not explained by baseline risk factors. CONCLUSION: Factors contributing to poorer physical and cognitive performance in similarly-aged black men and women could be targets to reduce excess mortality from cardiovascular disease, stroke, and kidney disease. More work is needed to identify factors contributing to cancer mortality disparities.

Introduction: Cumulative exposure to cardiovascular disease (CVD) risk factors during young adulthood is associated with later life CVD risk. Few prospective cohort studies measured exposures in young adulthood. We sought to develop and validate a method to impute trajectories of CVD risk factors across the life course. Methods: 36,546 participants (55% women, 25% black, average exams 5.1/participant) from 6 studies (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, and MESA) were included. Demographics and CVD risk factors (BMI, smoking, BP, lipids, glucose, medications for BP, lipids and glucose) were collected at each exam and harmonized across cohorts. We multiply imputed complete risk factor trajectories from age 18 to 99 years for each participant using an extension of linear mixed modeling (for continuous variables) and interval-censored survival modeling (for categorical variables), taking into account the multilevel structure of data. For validation, we randomly selected 25% of all participants and deleted their observed data for exam age 20-35, 50-65, or 80-95 years. We then imputed risk factor values for deleted age periods and compared imputed values with directly observed values. Results: Imputed values were relatively consistent with observed values for BMI, SBP, LDL, and glucose, particularly in young and middle ages ( Figure ). The mean (standard deviation) of the difference between imputed vs. observed values for BMI, SBP, LDL, and glucose were 0.1 (2.7) kg/m 2 , 0.9 (16.3) mm Hg, -1.1 (30.2) mg/dL, and -0.6 (23.0) mg/dL. The prevalence of imputed smoking, diabetes, and medications were also consistent with observed data. Conclusions: We demonstrated a validated method for estimating CVD risk factor trajectories across the life course. This approach may advance understanding of potential impact of cumulative early risk factor exposures on later life CVD risk, and inform primary prevention strategies over the life course. Figure. Mean and prevalence of observed vs. imputed risk factors by age periods 2

Background Data are sparse regarding the value of physical activity ( PA ) surveillance among older adults—particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Methods and Results Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home‐based activity data were collected by hip‐worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [ SD ] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84–0.96; P =0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65–0.89 [ P =0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow‐up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85–0.96 [ P =0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63–0.90 [ P =0.002]) were significantly associated with lower cardiovascular event rates. Conclusions Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01072500.

U.S. blacks have a higher risk of death than whites. This varies by cause of death; stroke, kidney disease and some cancers are higher in blacks. We evaluated cause-specific mortality risk factors in Health ABC to determine whether specific risk factors are more important for these causes of death in blacks than whites. Potential risk factors included: demographics, smoking, body mass index, chronic disease, physical function, and cognition. Among N=3075 participants ages 70–79 (41.7% black), average follow-up was 11.9 years. Underlying cause of death was adjudicated by committee and categorized as: cardiovascular disease, stroke, cancer, dementia, pulmonary, infection, kidney, and other cause. Median survival (95% confidence interval) among black men, white men, black women, and white women was 10.6 (10.0, 11.5), 12.8 (12.4, 13.4), 13.4 (12.6, 14.6), and 15.3 (14.8, 16.2) years, respectively. Adjusting for age and sex, blacks had higher risks of dying from: any cause (hazard ratio=1.32 (1.21, 1.44)), kidney disease (HR=2.10 (1.17, 3.78)), cancer (HR=1.35 (1.13, 1.62)), and stroke (HR=1.32 (0.97, 1.75)). Higher all-cause mortality risk among blacks was attenuated by further adjustment for gait speed (black race adjusted HR=1.06 (0.95, 1.17)) or digit symbol substitution test (black race adjusted HR=1.01 (0.91, 1.12)), but minimally by prevalent diseases (black race adjusted HR=1.25 (1.13, 1.38)). Gait speed also attenuated higher risk of kidney and stroke deaths among blacks, but not cancer deaths. Factors contributing to poorer physical and cognitive function in similarly aged community-dwelling ambulatory black men and women could be targets to reduce disparity and excess mortality.

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.Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia.Five academic medical centers in the United States.Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years.None.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; p0.0001). 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; p0.0001). 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.Hospitalization with pneumonia is associated with increased risk of dementia.

Background: Death certificate inaccuracy increases at older ages. The Long Life Family Study (LLFS) utilizes a physician adjudication committee to review the death certificate, medical records and a family narrative about cause of death. We report here the adjudication process and the prevalent underlying causes of death for a subsample of those who have died so far. Methods: We first describe the adjudication process. There were ~1,250 deaths in LLFS. We report underlying causes of death for a subset of proband generation subjects enrolled and evaluated by two LLFS study centers. Results: As of May 2019, we have adjudicated 190 deaths (98 male, 92 female) . Mean age 95 years (range 81-105 years). Top 5 causes of death for men: cancer (13%), coronary heart disease (CHD, 13%), dementia (13%), "other" (11%) and "unknown" (9%) and for women: dementia (21%), valvular heart disease (14%), coronary heart disease (12%), unknown (12%) and other (9%). Rate of death due to dementia was greater in women compared to men (CHI2 =7.33, p=0.006). Conclusions: In this pilot study, a significantly greater proportion of women died due to dementia compared to men. At least some portion of this difference may be due to the observation that women are known to survive chronic aging-related diseases more than men and thus have a greater opportunity to die from dementia at advanced ages. An additional cause to consider includes clinicians’ gender bias in ascribing diagnoses in the medical records that were relied upon as part of the adjudication process.

To the Editor: Cognitive, physical, and sensory limitations in older adults often limit informed decision-making in medical encounters.[1]However,older adults remaininterested in making informed healthcare choices,and patient-centered care will require innovations that promote engagement of older adults in care decisions.[2-3] The aim of this study was to determine the proportion of very old adults who felt adequately informed about their care following their most recent clinical encounter and identify correlates of informed care.

To evaluate the extent of variability in functional responses in participants in the Lifestyle Interventions and Independence for Elders (LIFE) study and to identify the relative contributions of intervention adherence, physical activity, and demographic and health characteristics to this variability.Secondary analysis.Multicenter institutions.A volunteer sample (N=1635) of sedentary men and women aged 70 to 89 years who were able to walk 400m but had physical limitations, defined as a Short Physical Performance Battery (SPPB) score of ≤9.Moderate-intensity physical activity (n=818) consisting of aerobic, resistance, and flexibility exercises performed both center-based (2times/wk) and home-based (3-4times/wk) sessions or health education program (n=817) consisting of weekly to monthly workshops covering relevant health information.Physical function (gait speed over 400m) and lower extremity function (SPPB score) assessed at baseline and 6, 12, and 24 months.Greater baseline physical function (gait speed, SPPB score) was negatively associated with change in gait speed (regression coefficient β=-.185; P.001) and change in SPPB score (β=-.365; P.001), whereas higher number of steps per day measured by accelerometry was positively associated with change in gait speed (β=.035; P.001) and change in SPPB score (β=.525; P.001). Other baseline factors associated with positive change in gait speed and/or SPPB score include younger age (P.001), lower body mass index (P.001), and higher self-reported physical activity (P=.002).Several demographic and physical activity-related factors were associated with the extent of change in functional outcomes in participants in the LIFE study. These factors should be considered when designing interventions for improving physical function in older adults with limited mobility.

Context End-of-life (EOL) treatment preferences among the very old (age 85+) may differ from preferences in younger aged populations because of high levels of symptom burden and disability and high risk of mortality. It is unclear if symptom burden or level of disability is more important for such preferences. Objectives To investigate whether distress from daily symptom burden was an independent correlate of EOL treatment preferences over two years of follow-up in people with median age 86 (participants) and 88 (reported by proxies) at baseline. Methods The End of Life in Very Old Age is an ancillary study to the Health, Aging and Body Composition study. At baseline in Year 15 of Health, Aging and Body Composition, 1038 participants and 189 proxies reported levels of symptom distress every quarter, as well as 0–8 EOL treatment preferences elicited once each year. Results At baseline, the mean (SD) count of EOL treatment preferences was 4.2 (2.1) in participants, and 2.9 (2.3) in proxies. EOL treatment preference was not associated with symptom distress. By contrast, black race, male gender, and reported ease walking a quarter mile were independently associated with more aggressive EOL treatment preferences. Conclusion Preferences for more aggressive EOL treatment were not related to daily symptom distress but were significantly more likely to be endorsed among those with better mobility, suggesting that disability is an independent predictor of EOL treatment preferences in the very old.

OBJECTIVES: To estimate the likelihood of, and factors associated with, recovery from exhaustion in older adults. DESIGN: Secondary analysis of a cohort study. SETTING: Six annual examinations in four U.S. communities. PARTICIPANTS: Four thousand five hundred eighty-four men and women aged 69 and older. MEASUREMENTS: Exhaustion was considered present when a participant responded �a moderate amount� or �most of the time� to either of two questions: �How often have you had a hard time getting going?� and �How often does everything seem an effort?� RESULTS: Of the 964 participants who originally reported exhaustion, 634 (65.8%) were exhaustion free at least once during follow-up. When data from all time points were considered, 48% of those who reported exhaustion were exhaustion free the following year. After adjustment for age, sex, race, education, and marital status, 1-year recovery was less likely in individuals with worse self-rated health and in those who were taking six or more medications or were obese, depressed, or had musculoskeletal pain or history of stroke. In proportional hazards models, the following risk factors were associated with more persistent exhaustion over 5 years: poor self-rated health, six or more medications, obesity, and depression. Recovery was not less likely in participants with a history of cancer or heart disease. CONCLUSION: Exhaustion is common in old age but is dynamic, even in those with a history of cancer and congestive heart failure. Recovery is especially likely in seniors who have a positive perception of their overall health, take few medications, and are not obese or depressed. These findings support the notion that resiliency is associated with physical and psychological well-being.

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

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.

Objectives—To evaluate both shared and unique risk factors for maintaining physical and cognitive function into the 9 th decade and beyond.

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— Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. Methods and Results— Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI. Conclusions— The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.

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.

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: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD). Design: Longitudinal cohort study. Setting: Four U.S. communities. Participants: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded. Measurements: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders. Results: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0–1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4–4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease. Conclusion: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.

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 ɛ4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P

Objective: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS). Methods: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists. Results: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer’s disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998–1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women. Conclusion: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.

Investigators have identified varying trajectories of disability before death, but it is unclear if disability trajectories among decedents and survivors differ among older adults.

Look AHEAD (Action for Health in Diabetes) was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow-up of 9.6 years was not reduced in the Intensive Lifestyle Group relative to the control group. This finding is discussed, with emphasis on its implications for design of trials and clinical treatment of obese persons with type 2 diabetes.

Objectives Assess functional trajectories as they differ by cause of death. Separate disability due to underlying chronic conditions from disability associated with end of life. Original Research Background: Investigators have identified varying trajectories of disability before death, but little is known about how decedent trajectories compare with those of matched survivors. Research Objectives: We examined self-reported disability at 6-month intervals before death among the 1,859 participants in the Health, Aging and Body Composition Study (Health ABC) who died before 2014 and made multiple comparisons with surviving participants. Methods: The original 3,075 study participants were recruited in 1997 from Medicare beneficiaries in Pittsburgh, PA, and Memphis, TN, who were at least 70 years of age and well functioning. Follow-up has continued for 17 years. Results: Disability trajectories among the decedents varied as expected. For example, difficulty dressing was reported 12 months before death by 27.5% of decedents with CHF or COPD compared with 8.1% who died from cancer (p

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, cerebrovascular, 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.

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.

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.

As part of its mission to provide geriatric training programs for rural and urban professionals, the Geriatric Education Center for Pennsylvania (GEC/PA) has adopted multiple strategies to attract participants to its multidisciplinary programs. Efforts include mailings, brochures, advertisements in professional newsletters, exhibits at conferences, contact through health care facilities, and a toll-free number. A survey was conducted to evaluate the different methods, and to determine the characteristics of the professionals attracted by these techniques. Nurses and social workers had the highest attendance; physicians had the poorest response. Hospitals and nursing homes were most represented, and were equally distributed between the private, public and government. Although individuals attending the urban sites only traveled short distances, most attending rural sites traveled over 50 miles. Brochures, mailings, and referrals by departmental supervisors were the best recruitment methods. Survey results r...

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.

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.

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.

THE adipocyte-derived peptide adiponectin has emerged as a potentially crucial molecule to cardiometabolic disorders (1). In the laboratory, adiponectin exhibits insulin-sensitizing, anti-inflammatory, and antiatherogenic properties (1). Yet, although its metabolic benefits have been confirmed in clinical studies, the relationship of circulating adiponectin to cardiovascular disease (CVD) in humans has been inconsistent (2). Although a protective association has been documented in younger adults without prevalent CVD (3), this has not been reproduced in groups with manifest heart disease (4,5) or in older adults (2), where the relationship has in fact been directionally opposite. This paradoxical adverse association with CVD and mortality in older adults has been replicated in different settings (6–8), but its basis remains unclear. It is well recognized from cross-sectional studies that circulating adiponectin is higher in older than in younger adults (9,10). Together with the observation that men with exceptional longevity harbor genetic variants associated with greater adiponectin levels (11), this has led to the proposition that the higher concentration with age could reflect a survivor bias (9,11). Contrariwise, the higher age-related levels and link to increased mortality suggest that resistance to adiponectin’s beneficial actions (12) or, alternatively, a response to adverse processes (13) or direct deleterious effects could be involved. Serial measurement of adiponectin in older adults would shed light on the basis for higher levels documented cross-sectionally. An important aspect of aging is a decline in cognitive and physical faculties, which serves as a harbinger of mortality (14). Obesity, dysglycemia, and CVD have distinct associations with circulating adiponectin levels, and all are strong determinants of functional decline (15). Defining the relationship of adiponectin to functional impairment in old age could help to clarify its reported association with mortality. To address these questions, we measured levels of adiponectin 9 years apart in a cohort surviving to advanced old age who underwent detailed assessment of functional status. Our objectives were to identify determinants of adiponectin change and to examine the association of adiponectin and its antecedent change with physical impairment and mortality in this older cohort.