Mary N. Haan

Depressive Symptoms and Risks of Coronary Heart Disease and Mortality in Elderly Americans

BackgroundSeveral epidemiological studies have associated depressive symptoms with cardiovascular disease. We investigated whether depressive symptoms constituted a risk for coronary heart disease (CHD) and total mortality among an apparently healthy elderly cohort. Methods and ResultsIn a prospective cohort of 5888 elderly Americans (≥65 years) who were enrolled in the Cardiovascular Health Study, 4493 participants who were free of cardiovascular disease at baseline provided annual information on their depressive status, which was assessed using the Depression Scale of the Center for Epidemiological Studies. These 4493 subjects were followed for 6 years for the development of CHD and mortality. The cumulative mean depression score was assessed for each participant up to the time of event (maximum 6-year follow-up). Using time-dependent, proportional-hazards models, the unadjusted hazard ratio associated with every 5-unit increase in mean depression score for the development of CHD was 1.15 (P =0.006); the ratio for all-cause mortality was 1.29 (P <0.0001). In multivariate analyses adjusted for age, race, sex, education, diabetes, hypertension, cigarette smoking, total cholesterol, triglyceride level, congestive heart failure, and physical inactivity, the hazard ratio for CHD was 1.15 (P =0.006) and that for all-cause mortality was 1.16 (P =0.006). Among participants with the highest cumulative mean depression scores, the risk of CHD increased by 40% and risk of death by 60% compared with those who had the lowest mean scores. ConclusionsAmong elderly Americans, depressive symptoms constitute an independent risk factor for the development of CHD and total mortality.

Central obesity and increased risk of dementia more than three decades later

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Subclinical Disease as an Independent Risk Factor for Cardiovascular Disease

BACKGROUND The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study. METHODS AND RESULTS A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes. CONCLUSIONS The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

Relationship Between ApoE, MRI Findings, and Cognitive Function in the Cardiovascular Health Study

BACKGROUND AND PURPOSE We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.

Area Characteristics and Individual-Level Socioeconomic Position Indicators in Three Population-Based Epidemiologic Studies

PURPOSE There is growing interest in incorporating area indicators into epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual-level data from three epidemiologic studies, we investigated how different area indicators are interrelated, how measures for different sized areas compare, and the relation between area and individual-level social position indicators. METHODS The interrelations between 13 area indicators of wealth/income, education, occupation, and other socioenvironmental characteristics were investigated using correlation coefficients and factor analyses. The extent to which block-group measures provide information distinct from census tract measures was investigated using intraclass correlation coefficients. Loglinear models were used to investigate associations between area and individual-level indicators. RESULTS Correlations between area measures were generally in the 0.5--0.8 range. In factor analyses, six indicators of income/wealth, education, and occupation loaded on one factor in most geographic sites. Correlations between block-group and census tract measures were high (correlation coefficients 0.85--0.96). Most of the variability in block-group indicators was between census tracts (intraclass correlation coefficients 0.72--0.92). Although individual-level and area indicators were associated, there was evidence of important heterogeneity in area of residence within individual-level income or education categories. The strength of the association between individual and area measures was similar in the three studies and in whites and blacks, but blacks were much more likely to live in more disadvantaged areas than whites. CONCLUSIONS Area measures of wealth/income, education, and occupation are moderately to highly correlated. Differences between using census tract or block-group measures in contextual investigations are likely to be relatively small. Area and individual-level indicators are far from perfectly correlated and provide complementary information on living circumstances. Differences in the residential environments of blacks and whites may need to be taken into account in interpreting race differences in epidemiologic studies.

Acculturation and the Prevalence of Depression in Older Mexican Americans: Baseline Results of the Sacramento Area Latino Study on Aging

OBJECTIVE: HTo determine the association between acculturation, immigration, and prevalence of depression in older Mexican Americans.

Prevalence of dementia in older latinos: the influence of type 2 diabetes mellitus, stroke, and genetic factors

OBJECTIVES: To estimate dementia prevalence in older Mexican Americans, determine the distribution of dementia by etiology, and evaluate the contribution of type 2 diabetes mellitus, stroke, and apolipoprotein E (ApoE) genotype to dementia.

Estrogen use, APOE, and cognitive decline Evidence of gene–environment interaction

Objective: APOE-ε4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-ε4 and cognitive decline. Method:— As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (≥65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on ≥2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. Results: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with ε4-negative women, ε4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and ε4 presence (p = 0.037). Among ε4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among ε4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in ε4-negative women but not in ε4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke. Conclusions: Estrogen use was associated with less cognitive decline among ε4-negative women but not ε4-positive women. Potential mechanisms, including carotid atherosclerosis, by which ε4 may interact with estrogen and cognition warrant further investigation.

Risk Factors for Dementia in the Cardiovascular Health Cognition Study

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’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 Ε4 (ApoE-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 ApoE-4 (2.1) were significant predictors of dementia. The combination of an ApoE-4 genotype, 3MSE score <90, ≧5 ventricular grade, ≧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, ApoE-4 and MRI of the brain are strong predictors of both dementia and of AD.

Age and education correction of Mini-Mental State Examination for English- and Spanish-speaking elderly

Previous research has shown that the Mini-Mental State Examination (MMS) is biased as a measure of cognitive impairment in minority and low-education patients. The purpose of this study was to (1) develop a statistical correction for effects of age and education and (2) test the efficacy of the statistically adjusted MMS (MMSAdj) as a screening test for dementia using different ethnic groups and education levels. We used a population-base community survey sample (n=590) composed of 46.6% Hispanics and 53.4% non-Hispanics to derive the statistical correction, defined as:MMSAdj = Raw MMS - (0.471 X [Education-12]) + (0.131 X [Age-70]). Ethnicity and language of test administration were not significantly related to MMSAdj in the community survey sample, but the raw MMS was strongly influenced by these factors. We used an independent sample (n=2,983) of patients evaluated through the California Alzheimers Disease Diagnostic and Treatment Centers to test the diagnostic accuracy of the MMS and the MMSAdj across low- and high-education groups and across whites, Hispanics, and blacks. Results showed greater stability of sensitivity and specificity across education levels and ethnic groups for the MMSAdj than for the raw MMS and suggest that the MMSAdj is a preferable measure of cognitive impairment for low- education and minority individuals.