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Background/Objectives Few studies have the requisite phenotypic information to define metabolic patterns that may inform our understanding of the pathophysiology and consequences of diabetes in older adults. We sought to characterize clusters of older adults on the basis of shared metabolic features. Design Population‐based prospective cohort study. Setting Four U.S. Cardiovascular Health Study field centers. Participants Individuals aged 65 and older taking no glucose‐lowering agents (N = 2,231). Measurements K‐means cluster analysis of 11 metabolic parameters (fasting and postload serum glucose and plasma insulin, fasting C‐peptide, body mass index, C‐reactive protein (CRP), estimated glomerular filtration rate (eGFR), albuminuria, carboxymethyl lysine (an advanced glycation end‐product), procollagen III N‐terminal propeptide (a fibrotic marker)) and their associations with incident cardiovascular disease, diabetes, disability, and mortality over 8 to 14.5 years of follow‐up and with measures of subclinical cardiovascular disease. Results A 6‐cluster solution provided robust differentiation into distinct, identifiable clusters. Cluster A (n = 739) had the lowest glucose and insulin and highest eGFR and the lowest rates of all outcomes. Cluster B (n = 419) had high glucose and insulin and intermediate rates of most outcomes. Cluster C (n = 118) had the highest insulin. Cluster D (n = 129) had the highest glucose with much lower insulin. Cluster E (n = 314) had the lowest eGFR and highest albuminuria. Cluster F (n = 512) had the highest CRP. Rates of CVD, mortality, and subclinical atherosclerosis were highest in clusters C, D, and E and were similar to rates in participants with treated diabetes. Incidence of disability was highest in Cluster C. Conclusion Clustering according to metabolic parameters identifies distinct phenotypes that are strongly associated with clinical and functional outcomes, even at advanced age.

Objectives To examine the association between inflammatory biomarkers and global cognitive function. Design Case-cohort. Setting Ginkgo Evaluation of Memory Study. Participants Individuals aged 75 and older free of neurological or neurodegenerative conditions recruited from 2000 to 2002 (N = 1,315). Measurements Outcome was cognitive function assessed using the modified Mini-Mental State Examination (3MSE) every 6 months for up to 7 years. Exposures were 10 biomarkers measured at baseline: interleukin-2, -6, and -10 (general systemic inflammation); pentraxin 3 (PTX3) and serum amyloid P (SAP) (vascular inflammation); plasminogen activator inhibitor-1, adiponectin, and resistin (metabolic function); receptor for advanced glycation endproduct (oxidative stress); and endothelin-1 (endothelial function). Associations between biomarkers and 3MSE scores (stratified according to mild cognitive impairment (MCI) at baseline) were analyzed using Cox regression (outcome: 3MSE decline of ≥5 points) and mixed-model regression. Bonferroni correction was used to determine significance threshold (P

OBJECTIVES: To determine the relative effect of five chronic conditions on four representative universal health outcomes. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study. PARTICIPANTS: Five thousand two hundred and ninety-eight community-living participants aged 65 and older. MEASUREMENTS: Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death. RESULTS: Each condition adversely affected self-rated health (P

OBJECTIVES: To determine the extent to which disease-related symptoms and impairments, which constitute measures of disease severity or targets of therapy, account for the associations between chronic diseases and universal health outcomes. DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS) and the Health, Aging and Body Composition Study (Health ABC). PARTICIPANTS: Five thousand six hundred fifty-four CHS members and 2,706 Health ABC members. MEASUREMENTS: Diseases included heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, and cognitive impairment. The universal health outcomes included self-rated health, basic and instrumental activities of daily living (ADLs and IADLs), and death. Disease-related symptoms and impairments included HF symptoms and ejection fraction (EF) for HF, Dyspnea Scale and forced expiratory volume in 1 second for COPD, joint pain for osteoarthritis, and executive function for cognitive impairment. RESULTS: The diseases were associated with the universal health outcomes (P

OBJECTIVES: To analyze baseline data on concomitant use of prescription drugs and dietary supplements in elderly people from the Ginkgo Evaluation of Memory (GEM) Study, in which information was collected on all drugs and supplements used by participant. DESIGN: Cross-sectional correlation analysis. SETTING: GEM Study sites in California, Maryland, North Carolina, and Pennsylvania. PARTICIPANTS: Three thousand seventy ambulatory individuals aged 75 and older enrolled between September 2000 and June 2002. MEASUREMENTS: Use of prescription drugs and dietary supplements identified through bottles brought to the clinic. RESULTS: Almost three-quarters (74.2%) of the cohort combined use of at least one prescription drug and one dietary supplement, with 32.5% using three or more prescription drugs and three or more supplements. The 15 most-prevalent prescription drugs exhibited substantial concomitant use with dietary supplements, ranging from 77.6% for diuretics to 93.6% for estrogen preparations. Although supplements were taken concomitantly with all classes of prescription drugs, the use of supplements was more likely in individuals using nonsteroidal anti-inflammatory drugs, thyroid drugs, and estrogens. The use of drugs for diabetes mellitus was negatively associated with the use of supplements, with most of this attributed to low use in those taking multivitamins, glucosamine and chondroitin, and echinacea. CONCLUSION: There is substantial concomitant use of prescription drugs and dietary supplements in elderly people. Further investigations are needed to define the clinical importance of this concomitant use, especially in elderly patients who consume multiple prescription drugs or have experienced an adverse event secondary to their prescription medications.

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal populationbased cohort of older adults. SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Five thousand eight hundred eightyeight adults aged 65 and older at baseline. MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated. RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes. CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a ‘‘healthy’’

OBJECTIVES: To analyze baseline data from the Ginkgo Evaluation of Memory (GEM) study, in which information was collected on the use of all dietary supplements. DESIGN: Cross-sectional regression analysis. SETTING: GEM study sites in California, Maryland, North Carolina, and Pennsylvania. PARTICIPANTS: The GEM study enrolled 3,072 ambulatory individuals aged 75 and older between September 2000 and June 2002. MEASUREMENTS: Self-reported use of dietary supplements and use identified through bottles brought to the clinic. RESULTS: Respectively, 59.4%, 66.6%, and 27.4% of the GEM study cohort used a multivitamin, at least one individual vitamin or mineral supplement, and some type of nonvitamin/nonmineral dietary supplement (NVNMDS). In logistic regression models, multivitamin use was associated with female sex, a higher income, a higher modified Mini-Mental State Examination score, difficulty with mobility, and asthma history; use of any other vitamin or mineral was associated with female sex, white race, nonsmoking, more years of schooling, difficulty walking, a history of osteoporosis, and reading health and senior magazines; and NVNMDS use was associated with residing in California, having difficulties with muscle strength, and reading health and senior magazines. CONCLUSION: There were substantial differences between individuals who used vitamins and minerals and those who used NVNMDS. These data require that trial investigators pay close attention to participant use of off-protocol dietary supplements. In addition, these findings may help identify elderly individuals likely to combine NVNMDS and prescription drugs.

OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups. DESIGN: Longitudinal, 6-year follow-up. PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study. MEASUREMENTS: Age, education (>10 years vs ≤10 years), Modified Mini-Mental State Examination score (3MS, ≤85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes. RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5–2.4 and 95% CI=1.4–2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4–7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7–9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2–3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE. CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

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 relationships between age and subclinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the “oldest old,” those 85 years and older. Design: Observational population-based study. Setting: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Participants: 5,201 men and women aged 65 years and older. Measurements: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65–74 years, 75–84 years, and 85+ years. Subgroups of participants with and without manifest CVD were also examined. Main Results: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups. Conclusions: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

To analyze baseline data on concomitant use of prescription drugs and dietary supplements in elderly people from the Ginkgo Evaluation of Memory (GEM) Study, in which information was collected on all drugs and supplements used by participant.Cross-sectional correlation analysis.GEM Study sites in California, Maryland, North Carolina, and Pennsylvania.Three thousand seventy ambulatory individuals aged 75 and older enrolled between September 2000 and June 2002.Use of prescription drugs and dietary supplements identified through bottles brought to the clinic.Almost three-quarters (74.2%) of the cohort combined use of at least one prescription drug and one dietary supplement, with 32.5% using three or more prescription drugs and three or more supplements. The 15 most-prevalent prescription drugs exhibited substantial concomitant use with dietary supplements, ranging from 77.6% for diuretics to 93.6% for estrogen preparations. Although supplements were taken concomitantly with all classes of prescription drugs, the use of supplements was more likely in individuals using nonsteroidal anti-inflammatory drugs, thyroid drugs, and estrogens. The use of drugs for diabetes mellitus was negatively associated with the use of supplements, with most of this attributed to low use in those taking multivitamins, glucosamine and chondroitin, and echinacea.There is substantial concomitant use of prescription drugs and dietary supplements in elderly people. Further investigations are needed to define the clinical importance of this concomitant use, especially in elderly patients who consume multiple prescription drugs or have experienced an adverse event secondary to their prescription medications.

To analyze baseline data from the Ginkgo Evaluation of Memory (GEM) study, in which information was collected on the use of all dietary supplements.Cross-sectional regression analysis.GEM study sites in California, Maryland, North Carolina, and Pennsylvania.The GEM study enrolled 3,072 ambulatory individuals aged 75 and older between September 2000 and June 2002.Self-reported use of dietary supplements and use identified through bottles brought to the clinic.Respectively, 59.4%, 66.6%, and 27.4% of the GEM study cohort used a multivitamin, at least one individual vitamin or mineral supplement, and some type of nonvitamin/nonmineral dietary supplement (NVNMDS). In logistic regression models, multivitamin use was associated with female sex, a higher income, a higher modified Mini-Mental State Examination score, difficulty with mobility, and asthma history; use of any other vitamin or mineral was associated with female sex, white race, nonsmoking, more years of schooling, difficulty walking, a history of osteoporosis, and reading health and senior magazines; and NVNMDS use was associated with residing in California, having difficulties with muscle strength, and reading health and senior magazines.There were substantial differences between individuals who used vitamins and minerals and those who used NVNMDS. These data require that trial investigators pay close attention to participant use of off-protocol dietary supplements. In addition, these findings may help identify elderly individuals likely to combine NVNMDS and prescription drugs.

To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups.Longitudinal, 6-year follow-up.Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study.Age, education (10 years vsor =10 years), Modified Mini-Mental State Examination score (3MS,or =85 vs85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes.White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5-2.4 and 95% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE.Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort.Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia.Four U.S. communities.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.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.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%).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.