@article {723, title = {Evaluation of dementia in the cardiovascular health cognition study.}, journal = {Neuroepidemiology}, volume = {22}, year = {2003}, month = {2003 Jan-Feb}, pages = {1-12}, abstract = {

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{\textquoteright}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.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Cross-Sectional Studies, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prevalence, Risk Factors, Sex Distribution}, issn = {0251-5350}, doi = {10.1159/000067110}, author = {Lopez, Oscar L and Kuller, Lewis H and Fitzpatrick, Annette and Ives, Diane and Becker, James T and Beauchamp, Norman} } @article {755, title = {Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.}, journal = {Arch Neurol}, volume = {60}, year = {2003}, month = {2003 Oct}, pages = {1385-9}, abstract = {

OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study.

DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort.

SETTING: Multicenter population study.

PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI.

MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type.

RESULTS: The overall prevalence of MCI was 19\% (465 of 2470 participants); prevalence increased with age from 19\% in participants younger than 75 years to 29\% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22\% (130 of 599 participants); prevalence of the MCI amnesic-type was 6\% and of the MCI multiple cognitive deficits-type was 16\%.

CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory Disorders, Neuropsychological Tests, Pennsylvania, Population, Psychiatric Status Rating Scales}, issn = {0003-9942}, doi = {10.1001/archneur.60.10.1385}, author = {Lopez, Oscar L and Jagust, William J and DeKosky, Steven T and Becker, James T and Fitzpatrick, Annette and Dulberg, Corinne and Breitner, John and Lyketsos, Constantine and Jones, Beverly and Kawas, Claudia and Carlson, Michelle and Kuller, Lewis H} } @article {724, title = {Risk factors for dementia in the cardiovascular health cognition study.}, journal = {Neuroepidemiology}, volume = {22}, year = {2003}, month = {2003 Jan-Feb}, pages = {13-22}, abstract = {

BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999.

METHODS: There were 480 incident dementia cases, 330 (69\%) were classified as Alzheimer{\textquoteright}s disease (AD).

RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95\% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes.

CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.

}, keywords = {Aged, Aged, 80 and over, Apolipoproteins E, Cardiovascular Diseases, Cognition Disorders, Dementia, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Odds Ratio, Predictive Value of Tests, Proportional Hazards Models, Risk Factors}, issn = {0251-5350}, doi = {10.1159/000067109}, author = {Kuller, Lewis H and Lopez, Oscar L and Newman, Anne and Beauchamp, Norman J and Burke, Greg and Dulberg, Corinne and Fitzpatrick, Annette and Fried, Linda and Haan, Mary N} } @article {756, title = {Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.}, journal = {Arch Neurol}, volume = {60}, year = {2003}, month = {2003 Oct}, pages = {1394-9}, abstract = {

OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study.

DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type.

SETTING: Multicenter population study.

PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort.

MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease.

RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores.

CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.

}, keywords = {Aged, Apolipoprotein E4, Apolipoproteins E, Brain, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Depressive Disorder, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mood Disorders, Pennsylvania, Population, Risk Factors}, issn = {0003-9942}, doi = {10.1001/archneur.60.10.1394}, author = {Lopez, Oscar L and Jagust, William J and Dulberg, Corinne and Becker, James T and DeKosky, Steven T and Fitzpatrick, Annette and Breitner, John and Lyketsos, Constantine and Jones, Beverly and Kawas, Claudia and Carlson, Michelle and Kuller, Lewis H} } @article {795, title = {Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.}, journal = {J Am Soc Nephrol}, volume = {15}, year = {2004}, month = {2004 Jul}, pages = {1904-11}, abstract = {

Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37\% increased risk of dementia (95\% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26\% increased risk (95\% CI = 1.02 to 1.60). These associations were present only among the 84\% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.

}, keywords = {Aged, Alzheimer Disease, Cardiovascular Diseases, Creatinine, Dementia, Dementia, Vascular, Female, Humans, Kidney, Kidney Diseases, Male, Muscles, Proportional Hazards Models}, issn = {1046-6673}, doi = {10.1097/01.asn.0000131529.60019.fa}, author = {Seliger, Stephen L and Siscovick, David S and Stehman-Breen, Catherine O and Gillen, Daniel L and Fitzpatrick, Annette and Bleyer, Anthony and Kuller, Lew H} } @article {810, title = {Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin.}, journal = {Cancer}, volume = {103}, year = {2005}, month = {2005 Jan 01}, pages = {76-84}, abstract = {

BACKGROUND: There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case-control study within the Cardiovascular Health Study cohort.

METHODS: In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n=174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1-9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age.

RESULTS: Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95\% confidence interval [95\% CI], 0.43-1.38), 0.73 (95\% CI, 0.41-1.30), and 0.67 (95\% CI, 0.37-1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels <4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95\% CI, 0.49-1.68), 0.47 (95\% CI, 0.25-0.94), and 0.65 (95\% CI, 0.35-1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical.

CONCLUSIONS: The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk.

}, keywords = {Aged, Aged, 80 and over, Carcinoma, Case-Control Studies, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Prostatic Neoplasms, Risk Factors}, issn = {0008-543X}, doi = {10.1002/cncr.20727}, author = {Chen, Chu and Lewis, S Kay and Voigt, Lynda and Fitzpatrick, Annette and Plymate, Stephen R and Weiss, Noel S} } @article {1055, title = {Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies.}, journal = {Ann Intern Med}, volume = {149}, year = {2008}, month = {2008 Oct 07}, pages = {461-71, W83-8}, abstract = {

BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.

PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.

DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit.

STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.

DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.

DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95\% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.

LIMITATIONS: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.

CONCLUSION: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

}, keywords = {Aged, Humans, Insulin-Like Growth Factor Binding Protein 2, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Male, Middle Aged, Prospective Studies, Prostatic Neoplasms, Risk Factors, Somatomedins}, issn = {1539-3704}, doi = {10.7326/0003-4819-149-7-200810070-00006}, author = {Roddam, Andrew W and Allen, Naomi E and Appleby, Paul and Key, Timothy J and Ferrucci, Luigi and Carter, H Ballentine and Metter, E Jeffrey and Chen, Chu and Weiss, Noel S and Fitzpatrick, Annette and Hsing, Ann W and Lacey, James V and Helzlsouer, Kathy and Rinaldi, Sabina and Riboli, Elio and Kaaks, Rudolf and Janssen, Joop A M J L and Wildhagen, Mark F and Schr{\"o}der, Fritz H and Platz, Elizabeth A and Pollak, Michael and Giovannucci, Edward and Schaefer, Catherine and Quesenberry, Charles P and Vogelman, Joseph H and Severi, Gianluca and English, Dallas R and Giles, Graham G and Stattin, P{\"a}r and Hallmans, G{\"o}ran and Johansson, Mattias and Chan, June M and Gann, Peter and Oliver, Steven E and Holly, Jeff M and Donovan, Jenny and Meyer, Fran{\c c}ois and Bairati, Isabelle and Galan, Pilar} } @article {1000, title = {Weight, mortality, years of healthy life, and active life expectancy in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Jan}, pages = {76-83}, abstract = {

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 population-based 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 eighty-eight 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" weight may be much higher than currently believed.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Body Mass Index, Body Weight, Female, Health Status Indicators, Humans, Life Expectancy, Life Style, Male, Prognosis, Risk Factors, Sex Factors, Survival Rate, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01500.x}, author = {Diehr, Paula and O{\textquoteright}Meara, Ellen S and Fitzpatrick, Annette and Newman, Anne B and Kuller, Lewis and Burke, Gregory} } @article {1084, title = {C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.}, journal = {Cancer Causes Control}, volume = {20}, year = {2009}, month = {2009 Sep}, pages = {1193-203}, abstract = {

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95\% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation.

}, keywords = {African Americans, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, European Continental Ancestry Group, Humans, Inflammation, Interleukin-6, Male, Polymorphism, Single Nucleotide, Prospective Studies, Prostatic Neoplasms, Risk Factors}, issn = {1573-7225}, doi = {10.1007/s10552-009-9320-4}, author = {Pierce, Brandon L and Biggs, Mary L and DeCambre, Marvalyn and Reiner, Alexander P and Li, Christopher and Fitzpatrick, Annette and Carlson, Christopher S and Stanford, Janet L and Austin, Melissa A} } @article {1097, title = {Using telephone and informant assessments to estimate missing Modified Mini-Mental State Exam scores and rates of cognitive decline. The cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {33}, year = {2009}, month = {2009}, pages = {55-65}, abstract = {

AIM: To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores.

METHODS: Comparability study on a subset of 405 participants, aged >or=70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants.

RESULTS: The TICS explained 67\% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered.

CONCLUSIONS: 3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Interviews as Topic, Longitudinal Studies, Male, Predictive Value of Tests, Psychiatric Status Rating Scales, Regression Analysis, Risk Factors, ROC Curve, United States}, issn = {1423-0208}, doi = {10.1159/000215830}, author = {Arnold, Alice M and Newman, Anne B and Dermond, Norma and Haan, Mary and Fitzpatrick, Annette} } @article {1349, title = {Kidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2).}, journal = {Am J Nephrol}, volume = {34}, year = {2011}, month = {2011}, pages = {512-8}, abstract = {

BACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied.

METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as >=3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (>=60 ml/min/1.73 m(2)).

RESULTS: Mean age was 72 {\textpm} 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95\% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline.

CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.

}, keywords = {Aged, Cardiovascular Diseases, Creatinine, Cystatin C, Disease Progression, Female, Geriatrics, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Middle Aged, Phospholipases A2, Risk Factors, Treatment Outcome}, issn = {1421-9670}, doi = {10.1159/000333045}, author = {Peralta, Carmen A and Katz, Ronit and Shlipak, Michael and Dubin, Ruth and DeBoer, Ian and Jenny, Nancy and Fitzpatrick, Annette and Koro, Carol and Kestenbaum, Bryan and Ix, Joachim and Sarnak, Mark and Cushman, Mary} } @article {5849, title = {Adiposity and cognitive decline in the cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {40}, year = {2013}, month = {2013}, pages = {274-81}, abstract = {

BACKGROUND: Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis, body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study.

METHODS: Cognitive performance was assessed with the modified Mini-Mental State Examination, the Digit Symbol Substitution Test, and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline.

RESULTS: The final sample was comprised of 2,681 women (57.9\%) and 1,949 men (42.1\%) aged 73 {\textpm} 5.2 and 73.9 {\textpm} 5.6 years, respectively. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease.

CONCLUSIONS: Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by preexisting conditions.

}, keywords = {Adiposity, Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cognition Disorders, Electric Impedance, Female, Humans, Male, Risk Factors, Waist Circumference, Waist-Hip Ratio}, issn = {1423-0208}, doi = {10.1159/000345136}, author = {Luchsinger, Jos{\'e} A and Biggs, Mary L and Kizer, Jorge R and Barzilay, Joshua and Fitzpatrick, Annette and Newman, Anne and Longstreth, William T and Lopez, Oscar and Siscovick, David and Kuller, Lewis} } @article {6246, title = {Gender and telomere length: systematic review and meta-analysis.}, journal = {Exp Gerontol}, volume = {51}, year = {2014}, month = {2014 Mar}, pages = {15-27}, abstract = {

BACKGROUND: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory.

METHODS: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression.

RESULTS: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95\% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error.

CONCLUSIONS: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.

}, keywords = {Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Male, Middle Aged, Sex Factors, Telomere}, issn = {1873-6815}, doi = {10.1016/j.exger.2013.12.004}, author = {Gardner, Michael and Bann, David and Wiley, Laura and Cooper, Rachel and Hardy, Rebecca and Nitsch, Dorothea and Martin-Ruiz, Carmen and Shiels, Paul and Sayer, Avan Aihie and Barbieri, Michelangela and Bekaert, Sofie and Bischoff, Claus and Brooks-Wilson, Angela and Chen, Wei and Cooper, Cyrus and Christensen, Kaare and De Meyer, Tim and Deary, Ian and Der, Geoff and Diez Roux, Ana and Fitzpatrick, Annette and Hajat, Anjum and Halaschek-Wiener, Julius and Harris, Sarah and Hunt, Steven C and Jagger, Carol and Jeon, Hyo-Sung and Kaplan, Robert and Kimura, Masayuki and Lansdorp, Peter and Li, Changyong and Maeda, Toyoki and Mangino, Massimo and Nawrot, Tim S and Nilsson, Peter and Nordfjall, Katarina and Paolisso, Giuseppe and Ren, Fu and Riabowol, Karl and Robertson, Tony and Roos, Goran and Staessen, Jan A and Spector, Tim and Tang, Nelson and Unryn, Brad and van der Harst, Pim and Woo, Jean and Xing, Chao and Yadegarfar, Mohammad E and Park, Jae Yong and Young, Neal and Kuh, Diana and von Zglinicki, Thomas and Ben-Shlomo, Yoav} }