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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., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

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 < .0025)., Results: In individuals with baseline MCI, PTX3 was associated with a 20% greater hazard of cognitive decline (95% confidence interval = 1.07-1.35), although this association was no longer statistically significant after adjustment for apolipoprotein (APO)E ε4 allele. Adiponectin was associated with faster rate of 3MSE decline in individuals without baseline MCI in mixed-model regression, but the association was similarly attenuated after adjustment for APOE-ε4., Conclusion: This study did not find strong evidence of the utility of the biomarkers evaluated for identifying individuals at risk of cognitive decline. Future studies investigating the association between PTX3, SAP, and adiponectin and 3MSE scores may be useful., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

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 < .001) and ADLs and IADLs (P < .001). For example, persons with HF performed 0.70 ± 0.08 fewer ADLs and IADLs than those without; persons with depression and persons with cognitive impairment performed 0.59 ± 0.04 and 0.58 ± 0.06 fewer activities, respectively, than those without these conditions. Depression, HF, COPD, and osteoarthritis were associated with 1.18 ± 0.04, 0.40 ± 0.08, 0.40 ± 0.05, and 0.57 ± 0.03 more symptoms, respectively, in individuals with these conditions than in those without. HF (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 1.97-4.10), COPD (2.62, 95% CI = 1.94-3.53), cognitive impairment (2.05, 95% CI = 1.47-2.85), and depression (1.47, 95% CI = 1.08-2.01) were each associated with death within 2 years. Several paired combinations of conditions had synergistic effects on ADLs and IADLs. For example, individuals with HF plus depression performed 2.0 fewer activities than persons with neither condition, versus the 1.3 fewer activities expected from adding the effects of the two conditions together., Conclusion: Universal health outcomes may provide a common metric for measuring the effects of multiple conditions and their treatments. The varying effects of the conditions across universal outcomes could inform care priorities., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

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 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 < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =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 epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%)., Conclusion: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.