Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Racial disparities in adult all-cause and cause-specific mortality among us adults: mediating and moderating factors.

BACKGROUND: Studies uncovering factors beyond socio-economic status (SES) that would explain racial and ethnic disparities in mortality are scarce. METHODS: Using prospective cohort data from the Third National Health and Nutrition Examination Survey (NHANES III), we examined all-cause and cause-specific mortality disparities by race, mediation through key factors and moderation by age (20-49 vs. 50+), sex and poverty status. Cox proportional hazards, discrete-time hazards and competing risk regression models were conducted (N = 16,573 participants, n = 4207 deaths, Median time = 170 months (1-217 months)). RESULTS: Age, sex and poverty income ratio-adjusted hazard rates were higher among Non-Hispanic Blacks (NHBs) vs. Non-Hispanic Whites (NHW). Within the above-poverty young men stratum where this association was the strongest, the socio-demographic-adjusted HR = 2.59, p < 0.001 was only partially attenuated by SES and other factors (full model HR = 2.08, p = 0.003). Income, education, diet quality, allostatic load and self-rated health, were among key mediators explaining NHB vs. NHW disparity in mortality. The Hispanic paradox was observed consistently among women above poverty (young and old). NHBs had higher CVD-related mortality risk compared to NHW which was explained by factors beyond SES. Those factors did not explain excess risk among NHB for neoplasm-related death (fully adjusted HR = 1.41, 95 % CI: 1.02-2.75, p = 0.044). Moreover, those factors explained the lower risk of neoplasm-related death among MA compared to NHW, while CVD-related mortality risk became lower among MA compared to NHW upon multivariate adjustment. CONCLUSIONS: In sum, racial/ethnic disparities in all-cause and cause-specific mortality (particularly cardiovascular and neoplasms) were partly explained by socio-demographic, SES, health-related and dietary factors, and differentially by age, sex and poverty strata.

An analytical strategy for challenging members of the microplastic family: Particles from anti-corrosion coatings.

Potentially hazardous particles from paints and functional coatings are an overlooked fraction of microplastic (MP) pollution since their accurate identification and quantification in environmental samples remains difficult. We have applied the most relevant techniques from the field of microplastic analysis for their suitability to chemically characterize anti-corrosion coatings containing a variety of polymer binders (LDIR, Raman and FTIR spectroscopy, Py-GC/MS) and inorganic additives (ICP-MS/MS). We present the basis of a possible toolbox to study the release and fate of coating particles in the (marine) environment. Our results indicate that, due to material properties, spectroscopic methods alone appear to be unsuitable for quantification of coating/paint particles and underestimate their environmental abundance. ICP-MS/MS and an optimized Py-GC/MS approach in combination with multivariate statistics enables a straightforward comparison of the multi-elemental and organic additive fingerprints of paint particles. The approach can improve the identification of unknown particles in environmental samples by an assignment to different typically used coating types. In future, this approach may facilitate allocation of emission sources of different environmental paint/coating particles. Indeed, future work will be required to tackle various remaining analytical challenges, such as optimized particle extraction/separation of environmental coating particles.

Depressive symptoms are associated with weight gain among women.

BACKGROUND: Many studies have linked depression and obesity; few have more than two assessments of depressive symptoms and adiposity to address the potential bidirectional relationship between adiposity and depressive symptoms from young adulthood through old age. We tested whether baseline depressive symptoms are associated with changes in weight, whether baseline adiposity is associated with changes in depressive symptoms, and whether these associations vary by sex. METHOD: Participants (n=2251; 47% female) were from the Baltimore Longitudinal Study of Aging (BLSA). Using hierarchical linear modeling (HLM) on 30 years of data, the trajectory of adiposity and depressive symptoms over adulthood was estimated from >10 000 observations (mean=4.5 assessments per participant) of body mass index (BMI; kg/m2), waist circumference and hip circumference and >10 000 observations (mean=4.5 assessments per participant) of the Center for Epidemiological Studies Depression Scale (CES-D). Baseline depressive symptoms and adiposity were then tested as predictors of the trajectory of adiposity and depressive symptoms respectively. Additional analyses tested for sex-specific associations. RESULTS: Sex moderated the association between depressive symptoms and weight gain such that women who experienced depressed affect had greater increases in BMI (b(interaction)=0.12, S.E.=0.04), waist (b(interaction)=0.22, S.E.=0.10) and hip circumference (b(interaction)=0.20, S.E.=0.07) across the adult lifespan, controlling for relevant demographic and behavioral covariates. Baseline adiposity was unrelated to the trajectory of depressive symptoms (median b=0.00) for both sexes. CONCLUSIONS: Women who experience symptoms of depression tend to gain more weight across adulthood than men who experience such symptoms. Whether an individual was normal weight or overweight was unrelated to changes in depressive symptoms across adulthood.

Multiple Influences on Cognitive Function Among Urban-Dwelling African Americans.

This study examined multiple influences on cognitive function among African Americans, including education, literacy, poverty status, substance use, depressive symptoms, and cardiovascular disease (CVD) risk factors. Baseline data were analyzed from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants were 987 African Americans (mean age 48.5 years, SD = 9.17) who completed cognitive measures assessing verbal learning and memory, nonverbal memory, working memory, verbal fluency, perceptuo-motor speed, attention, and cognitive flexibility. Using preplanned hierarchical regression, cognitive performance was regressed on the following: (1) age, sex, education, poverty status; (2) literacy; (3) cigarette smoking, illicit substance use; (4) depressive symptoms; and (5) number of CVD risk factors. Results indicated that literacy eliminated the influence of education and poverty status in select instances, but added predictive utility in others. In fully adjusted models, results showed that literacy was the most important influence on cognitive performance across all cognitive domains (p < .001); however, education and poverty status were related to attention and cognitive flexibility. Depressive symptoms and substance use were significant predictors of multiple cognitive outcomes, and CVD risk factors were not associated with cognitive performance. Overall, findings underscore the need to develop cognitive supports for individuals with low literacy, educational attainment, and income, and the importance of treating depressive symptoms and thoroughly examining the role of substance use in this population.

Dietary Protein Intake and Overall Diet Quality Are Associated with Handgrip Strength in African American and White Adults.

OBJECTIVE: To determine the association of handgrip strength (HS) with protein intake, diet quality, and nutritional and cardiovascular biomarkers in African American and White adults. DESIGN: Cross-sectional wave 3 (2009-2013) of the cohort Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. PARTICIPANTS: Socioeconomically diverse urban population of 2,468 persons aged 33 to 71 years. MEASUREMENTS: Socio-demographic correlates, dietary intakes and biomarkers, HS, physical performance measures were collected. HS was measured using a dynamometer with the dominant hand. Functional measures included chair, tandem, and single leg stands. Two 24-hour recalls were collected using the US Department of Agriculture Automated Multiple Pass Method. The total protein intake and diet quality, evaluated by adherence to the DASH eating plan and Healthy Eating Index-2010, were calculated. Biomarkers included nutritional anemia, and serum levels of albumin, cholesterol, magnesium, and glucose. RESULTS: The mean ±SE age of the sample was 52.3±0.2 years. Approximately 61% were African American and 57% were women. The mean ±SE HS of women was 29.1±0.2kg and for men was 45.9±0.4 kg. Protein, gm, per kg body weight for the women was 0.94±0.02 compared to 1.16 ±0.02 for men. After adjusting for socio-demographic factors, hypertension, and diabetes, HS/BMI ratio was significantly associated with protein intake per kg body weight (p<0.001) and diet quality, assessed by either the DASH adherence (p=0.009) or Health Eating Index-2010 (p=0.031) scores. For both men and women, participants in the upper tertile of HS maintained a single leg and tandem stances longer and completed 5 and 10 chair stands in shorter time compared to individuals in the lower HS tertile. Of the nutritional status indicators, the percent of men in the upper HS tertile with low serum magnesium and albumin, was significantly lower than those in the lower HS tertile [magnesium,7.4% vs 16.1%; albumin, 0.4% vs 4.5%]. The only difference observed for women was a lower percent of diabetes (14.4% for the upper HS tertile compared to 20.5% for the lower HS tertile. CONCLUSIONS: The findings confirm the role of protein and a healthful diet in the maintenance of muscle strength. In this community sample, HS was significantly associated with other physical performance measures but did not appear to be strongly associated with indicators of nutritional risk. These findings support the use of HS as a proxy for functional status and indicate the need for research to explore its role as a predictor of nutritional risk.

Coordinately up-regulated genes in ovarian cancer.

A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and therapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expression. However, these methods do not allow highly quantitative analysis of gene expression on a large number of specimens. Here, we have used quantitative real-time RT-PCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glutathione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growth factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteinase 3, folate receptor 1, S100A2, signal transducer and activator of transcription 1, secretory leukocyte protease inhibitor, apolipoprotein E, and ceruloplasmin. All of the genes were found overexpressed, some at extremely high levels, in the vast majority of ovarian carcinomas irrespective of the subtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some of the genes studied here may thus represent targets for early detection ovarian cancer. The gene expression patterns were not associated with age at diagnosis, stage, or K-ras mutation status in ovarian cancer. We find that several genes are coordinately regulated in ovarian cancer, likely representing the fact that many genes are activated as part of common signaling pathways or that extensive cross-talk exists between several pathways in ovarian cancer. A statistical analysis shows that genes commonly up-regulated in ovarian cancer may result from the aberrant activation of a limited number of pathways, providing promising targets for novel therapeutic strategies.

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults.

Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=-0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.

The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men.

BACKGROUND: The observation that dehydroepiandrosterone (DHEA) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition. In the United States, DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes. OBJECTIVE: To investigate the relationship between age-associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and declines in neuropsychological performance in a prospective, longitudinal study. METHODS: The subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at the initial visit, and they were followed up for as long as 31 years (mean, 11. 55 years), with biennial reassessments of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were the results of cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency tests, and measures of visuomotor scanning and attention. Serum DHEA-S concentrations were determined by standard radioimmunoassay. RESULTS: Neither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline. A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years. CONCLUSION: Our longitudinal results augment those of previous prospective studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men.

Total serum cholesterol, atherogenic indices and their longitudinal association with depressive symptoms among US adults.

Serum cholesterol, both total and lipoprotein fractions, has been associated with mid- and late-life depression. Using longitudinal data on a large and ethnically diverse sample of urban adults, the associations of serum lipid profile measured by high or low total cholesterol (TC; >200 mg dl(-1); <160 mg dl(-1)) and by atherogenic indices, namely high total cholesterol and low-density lipoprotein cholesterol relative to high-density lipoprotein cholesterol, with change in total and domain-specific depressive symptoms over time were examined. Findings were compared by sex. (Hypothesis 1) In addition, baseline depressive symptoms as predictors for longitudinal change in lipid profile trajectory were tested. (Hypothesis 2) Mixed-effects regression analyses stratified by sex was used. Sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (Men: n=826 ; n'=1319; Women: n=1099 ; n'=1817); Hypothesis 2 (Men: n=738; n'=1230; Women: n=964; n'=1678). As hypothesized, a higher level of atherogenic indices was linked to faster increase in depressive symptom scores, particularly depressed affect and interpersonal problems, though this relationship was found only among women. Among men a U-shaped relationship between baseline TC and longitudinal increase in somatic complaints and a direct link between low TC and longitudinal putative improvement in positive affect was found. On excluding statin users among women, low TC was associated with slower increase in depressed affect over time, whereas high TC was associated with faster increase in interpersonal problems. In summary, atherogenic indices were directly linked to faster increase in depressive symptoms among women only. More studies are needed to explain these sex-specific associations.

Age differences in spatial memory in a virtual environment navigation task.

The use of virtual environment (VE) technology to assess spatial navigation in humans has become increasingly common and provides an opportunity to quantify age-related deficits in human spatial navigation and promote a comparative approach to the neuroscience of cognitive aging. The purpose of the present study was to assess age differences in navigational behavior in a VE and to examine the relationship between this navigational measure and other more traditional measures of cognitive aging. Following pre-training, participants were confronted with a VE spatial learning task and completed a battery of cognitive tests. The VE consisted of a richly textured series of interconnected hallways, some leading to dead ends and others leading to a designated goal location in the environment. Compared to younger participants, older volunteers took longer to solve each trial, traversed a longer distance, and made significantly more spatial memory errors. After 5 learning trials, 86% of young and 24% of elderly volunteers were able to locate the goal without error. Performance on the VE navigation task was positively correlated with measures of mental rotation and verbal and visual memory.

Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.

OBJECTIVE: This study examined the effects of hormone-replacement therapy on memory and other cognitive abilities in cognitively intact older women. METHOD: This prospective observational study in nondemented postmenopausal women aged 50-89 from the Baltimore Longitudinal Study of Aging involved study groups consisting of 103 women who were receiving oral or transdermal estrogen-replacement therapy (44 of whom were receiving adjuvant progesterone) and 81 women who had never received such therapy. Groups were naturally matched on education, health status, depressive symptoms, annual income, and general verbal ability. To restrict the study group to cognitively healthy women, prospective clinical data were used to exclude women who developed dementia up to 5 years after assessment. Data were cross-sectional. Multivariate analysis of variance and follow-up univariate analyses of variance were performed to compare those women who were receiving and those who had never received hormone-replacement therapy on measures of verbal memory, figural memory, mental rotations, attention, and working memory. RESULTS: The women receiving hormone-replacement therapy performed significantly better on measures of verbal learning and memory than did those who had never received hormones, but there were no significant differences in scores on other cognitive tests. Specific aspects of memory performance, including encoding and retrieval, were superior among the women receiving hormone therapy. CONCLUSIONS: These findings, based on groups of women who were receiving and had never received hormone-replacement therapy and who were naturally matched on health and cognitive status, suggest that hormone-replacement therapy may have a selective beneficial effect on verbal memory in older nondemented women.

Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis.

OBJECTIVE: It has been reported that the human temperament dimensions of novelty seeking and harm avoidance are associated with polymorphisms in the D(4) dopamine receptor gene (D4DR) and the serotonin-transporter-linked promoter region (5-HTTLPR), respectively. Although these findings are consistent with Cloninger's hypothesized psychobiological model of temperament and character, many studies failed to replicate these findings. In the present study the authors tested whether the psychobiological model taps the genetic architecture of personality by exploring associations between these candidate genes and the dimensions of the Temperament and Character Inventory and by examining its phenotypic structure. METHOD: Of the 946 male and female participants in the Baltimore Longitudinal Study of Aging to whom the Temperament and Character Inventory was administered, 587 were genotyped for a polymorphism with a 48-base-pair repeat in the D4DR gene and 425 were genotyped for a 44-base-pair insertion or deletion in the 5-HTTLPR polymorphism. RESULTS: There was no significant association between D4DR polymorphisms and novelty seeking. The authors also failed to find an association between 5-HTTLPR polymorphisms and harm avoidance. The factor structure of the Temperament and Character Inventory did not reveal the hypothesized phenotypic structure. CONCLUSIONS: This investigation produced no support for the temperament-character model at either the biological or psychological level.

Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). BACKGROUND: The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. METHODS: Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. RESULTS: The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. CONCLUSION: Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.

Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect?

Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk of Alzheimer's disease. In the present study we test the hypothesis that ERT may have a protective effect on memory in nondemented women. Data on hormonal status and memory were examined in 288 postmenopausal women in the Baltimore Longitudinal Study of Aging. One hundred sixteen women who reported that they were receiving ERT during a cognitive assessment were compared with 172 women who had never received ERT. Women who were receiving ERT had fewer errors on the Benton Visual Retention Test (BVRT), a measure of short-term visual memory, visual perception, and constructional skills. Furthermore, ERT appeared to protect against age changes in BVRT performance in a subgroup of 18 women for whom BVRT data were available before and during treatment with ERT. These findings suggest that ERT may protect against memory decline in nondemented postmenopausal women and offer further support for a beneficial role of estrogen on cognitive function in aging women.

Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype.

The epsilon4 allele of the apolipoprotein E (APOE) gene confers an increased risk for the development of AD. The authors compared longitudinal rates of change in hippocampal volume as a function of APOE genotype in nondemented elderly individuals. Rate of volumetric loss was significantly greater among epsilon4+ compared with epsilon4- individuals. These results indicate that individuals positive for the APOE epsilon4 allele may show a greater rate of hippocampal atrophy than their epsilon4- counterparts, even in the absence of a diagnosis of AD.

A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

Previous reports have suggested that estrogen replacement therapy (ERT) in women may exert a protective effect on their risk of developing Alzheimer's disease (AD). We investigated this relationship in the Baltimore Longitudinal Study of Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by the National Institute on Aging. The sample consisted of 472 post- or perimenopausal women followed for up to 16 years in the BLSA. We documented ERT prospectively at each BLSA visit, and we categorized women who had used oral or transdermal estrogens at anytime as ERT users. We used Cox proportional hazards models with time-dependent covariates to estimate the relative risk of developing AD after ERT as compared with women who had not used estrogen replacement. Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34 incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine estrogen users. After adjusting for education, the relative risk for AD in ERT users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen. Our data did not show an effect for duration of ERT usage. Our finding offers additional support for a protective influence of estrogen in AD. Randomized clinical trials are necessary to confirm this association, which could have significant public health impact.

Is the apoE4 allele an independent predictor of coronary events?

PURPOSE: Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain. SUBJECTS AND METHODS: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52+/-17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level. RESULTS: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Coronary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P <0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P<0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62). CONCLUSION: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels.

Effects of age, hypertension history, and neuroticism on health perceptions.

The effects of measured blood pressure, history of hypertension diagnosis, age, and neuroticism on number of somatic complaints and self-rated health were examined in a sample of 970 non-health-care-seeking adult men and women. Significant differences in number of somatic complaints and self-rated health were found due to age, neuroticism, and history of hypertension diagnosis. Measured blood pressure, however, was unrelated to both measures of health perception. With the exception of the effect of neuroticism on somatic complaints, the effects of the independent variables on health perceptions were rather small in magnitude and explained only small proportions of the variance. Age differences had a particularly weak effect on health perceptions, accounting for less variance than either neuroticism or history of hypertension diagnosis. A significant interaction of neuroticism with awareness of hypertension was found, but only for number of somatic complaints. These results suggest that health perception is a complex, multidimensional construct. The relatively weak influence of hypertension diagnosis on health perception may account for the difficulties in maintaining patient compliance with antihypertensive treatment.

Association of radiographic features of osteoarthritis of the knee with knee pain: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To examine the association between self-reported knee pain and radiographic features of osteoarthritis (OA) of the knee. METHODS: A sample of participants in the Baltimore Longitudinal Study of Aging (452 Caucasian males and 223 Caucasian females) completed questionnaires and underwent a standing radiograph of both knees at the same biennial visit between 1984 and 1989. Radiographs were interpreted using both the Kellgren-Lawrence and individual features scales. Odds ratios were calculated for the association of radiographic features with knee pain after adjustment for age, sex, and body mass index. RESULTS: Overall, 156 (23%) persons reported ever having knee pain, and 104 (15%) reported current knee pain (within the previous year). Both ever knee pain and current knee pain were significantly associated with the presence of definite knee OA (Kellgren-Lawrence grade > or = 2) and with the presence of all individual features. There was a direct relationship between all measures of severity of radiographic OA and knee pain. CONCLUSION: These data demonstrate that radiographic features of knee OA are significantly associated with knee pain. The data also support the continued use of the Kellgren-Lawrence grading scale for defining knee OA in population studies.