Susan B. Muldoon

Effects of Blood Lead Levels on Cognitive Function of Older Women

Elevated blood lead concentrations are known to have detrimental effects on neuropsychological function in both children and occupational cohorts of men and women. Although it is generally accepted that lead exposure at low levels is more dangerous for infants and children than for adults, the issue of the lowest level of exposure at which lead causes deleterious health effects in adults is yet to be solved. There is no available data on the role of lead exposure in cognitive dysfunction in nonoccupational cohorts of older persons. In the current study, we examined the cross-sectional relationship between blood lead levels and a variety of measures of neuropsychological function in a large cohort of elderly women recruited at both urban and rural sites. This study of elderly women demonstrates that blood lead levels as low as 8 micrograms/dl were significantly associated with poorer cognitive function as measured by certain neuropsychological tests. Even a slight decrement in cognition would have a large public health impact due to the large number of elderly at risk.

Association of blood lead concentrations with mortality in older women: a prospective cohort study

BackgroundBlood lead concentrations have been associated with increased risk of cardiovascular, cancer, and all-cause mortality in adults in general population and occupational cohorts. We aimed to determine the association between blood lead, all cause and cause specific mortality in elderly, community residing women.MethodsProspective cohort study of 533 women aged 65–87 years enrolled in the Study of Osteoporotic Fractures at 2 US research centers (Baltimore, MD; Monongahela Valley, PA) from 1986–1988. Blood lead concentrations were determined by atomic absorption spectrometry. Using blood lead concentration categorized as < 8 μg/dL (0.384 μmol/L), and ≥ 8 μg/dL (0.384 μmol/L), we determined the relative risk of mortality from all cause, and cause-specific mortality, through Cox proportional hazards regression analysis.ResultsMean blood lead concentration was 5.3 ± 2.3 μg/dL (range 1–21) [0.25 ± 0.11 μmol/L (range 0.05–1.008)]. After 12.0 ± 3 years of > 95% complete follow-up, 123 (23%) women who died had slightly higher mean (± SD) blood lead 5.56 (± 3) μg/dL [0.27(± 0.14) μmol/L] than survivors: 5.17(± 2.0) [0.25(± 0.1) μmol/L] (p = 0.09). Women with blood lead concentrations ≥ 8 μg/dL (0.384 μmol/L), had 59% increased risk of multivariate adjusted all cause mortality (Hazard Ratio [HR], 1.59; 95% confidence interval [CI], 1.02–2.49) (p = 0.041) especially coronary heart disease (CHD) mortality (HR = 3.08 [CI], (1.23–7.70)(p = 0.016), compared to women with blood lead concentrations < 8 μg/dL(< 0.384 μmol/L). There was no association of blood lead with stroke, cancer, or non cardiovascular deaths.ConclusionWomen with blood lead concentrations of ≥ 8 μg/dL (0.384 μmol/L), experienced increased mortality, in particular from CHD as compared to those with lower blood lead concentrations.

Relationship of blood lead levels to incident nonspine fractures and falls in older women: the study of osteoporotic fractures.

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65–87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in μg/dl) were measured in 1990–1991 by atomic absorption spectrophotometry and classified as “low” (≤3; lower 15th percentile, referent); “medium” (4–7); or “high” (≥8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 ± 2.3 (SD) μg/dl (range, 1–21 μg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p < 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.

Mortality patterns among Paducah Gaseous Diffusion Plant workers.

Objective: To determine whether Paducah Gaseous Diffusion Plant workers had mortality patterns that differed from the general US population and to investigate whether mortality patterns were associated with job title or workplace exposures. Methods: A retrospective occupational cohort mortality study was conducted on 6759 workers. Standardized mortality ratio analyses compared the cohort with the referent US population. Internal comparisons producing standardized rate ratios were conducted by job title, metal exposure, and cumulative internal and external radiation exposures. Results: Overall mortality and cancer rates were lower than the referent population, reflecting a strong healthy worker effect. Individual not significant standardized mortality ratios and standardized rate ratios were noted for cancers of the lymphatic and hematopoietic tissue. Conclusions: Although relatively low exposures to radiation and metals did not produce statistically significant health effects, no significant elevations for lymphatic and hematopoietic cancers were consistent with previous studies of nuclear workers.

Occupational exposure to trichloroethylene and cancer risk for workers at the Paducah Gaseous Diffusion Plant.

ObjectiveThe Paducah Gaseous Diffusion Plant (PGDP) became operational in 1952; it is located in the western part of Kentucky. We conducted a mortality study for adverse health effects that workers may have suffered while working at the plant, including exposures to chemicals.Materials and MethodsWe studied a cohort of 6820 workers at the PGDP for the period 1953 to 2003; there were a total of 1672 deaths to cohort members. Trichloroethylene (TCE) is a specific concern for this workforce; exposure to TCE occurred primarily in departments that clean the process equipment. The Life Table Analysis System (LTAS) program developed by NIOSH was used to calculate the standardized mortality ratios for the worker cohort and standardized rate ratio relative to exposure to TCE (the U.S. population is the referent for ageadjustment). LTAS calculated a significantly low overall SMR for these workers of 0.76 (95% CI: 0.72–0.79). A further review of three major cancers of interest to Kentucky produced significantly low SMR for trachea, bronchus, lung cancer (0.75, 95% CI: 0.72–0.79) and high SMR for Non-Hodgkin’s lymphoma (NHL) (1.49, 95% CI: 1.02–2.10).ResultsNo significant SMR was observed for leukemia and no significant SRRs were observed for any disease. Both the leukemia and lung cancer results were examined and determined to reflect regional mortality patterns. However, the Non-Hodgkin’s Lymphoma finding suggests a curious amplification when living cases are included with the mortality experience.ConclusionsFurther examination is recommended of this recurrent finding from all three U.S. Gaseous Diffusion plants.

Ladybug hypersensitivity among residents of homes infested with ladybugs in Kentucky

BACKGROUND There have been isolated case reports of hypersensitivity to the ladybug species Harmonia axyridis. Entomologists now report a rapid increase in ladybug numbers, giving rise to increasing complaints of residential infestations. OBJECTIVES To determine whether ladybug infestation of homes causes hypersensitivity among residents and to estimate the prevalence of self-reported ladybug allergy in this population. METHODS This pilot observational study was conducted using an anonymous survey. RESULTS The participation rate was 59% (99/167). The incidence of self-reported allergy symptoms in this population was 77% (95% confidence interval [CI], 67%-85%). The prevalence of self-reported ladybug allergy was 50% (95% CI, 39%-60%). Of all the respondents, 19% (95% CI, 12%-28%) reported allergy symptoms on direct contact with ladybugs and 31% (95% CI, 22%-41%) reported the use of extra allergy medications during times of infestation. The correlation between worsening of allergy symptoms and time of infestation was significant for spring, fall, and winter infestations (P = .02, P = .001, and P < .001, respectively). CONCLUSIONS To our knowledge, this is the first study to estimate the prevalence of ladybug hypersensitivity, which was found to be 50% by self-report among people with home infestations. These results suggest that the ladybug could be a significant cause of respiratory allergy in heavily infested homes. Further studies using diagnostic testing to confirm allergy are now indicated. We recommend that patients with spring, fall, and winter allergies be asked about ladybug infestation and that ladybug reagents be made available for diagnostic testing.

Cognitive Decline and Polypharmacy in an Elderly Population

To the editor: The Department of Health & Human Services estimates that by 2030 there will be 72.1 million individuals 65 or older in the U.S.1 The prevalence of Mild Cognitive Impairment (MCI) in the elderly population is between 3% and 19%, with an incidence of 8–58 per 1000 per year, and a risk of developing dementia of 11–33% over 2 years.2 The higher prevalence of chronic diseases makes this population at a higher risk of taking multiple medications. Polypharmacy, defined most commonly as the concomitant use of 5 or more medications, is a poorly studied factor in relation with MCI, but may also play an important role.3 Jyrkka et al. performed a follow-up study in a Finnish population of 294 elderly people between 2004 and 2007, recording the use of medications and the cognitive function of participants.3 The authors observed that excessive polypharmacy, defined as the concomitant use of 10 or more medications, was associated with a decline in the cognitive capacity measured by the Mini-Mental State Examination (MMSE) compared with the non-polypharmacy group. Considering the dearth of scientific studies analyzing the effects of polypharmacy on cognitive decline, particularly in the American population, this study examines data from the New Mexico Aging Process Study (NMAPS) to further investigate the effects of polypharmacy on cognitive status changes. We developed a longitudinal cohort study using the data from 572 participants from NMAPS to measure the impact of polypharmacy on MMSE scores and risk of MCI. Mixed linear regression multivariable models and generalized estimating equations were used to estimate these associations, adjusting for gender, age at baseline, Charlson Comorbidity Index (CCI), presence of ApoE e4 allele, body mass index (BMI), and hypertension. Most of the study subjects were female (63.6%), white (88.5%), and married (66.6%). In addition, 47.2% of the study population had between 12 and 16 years of education and 36.2% had more than 16 years of education. Polypharmacy was associated with a 0.11±0.09 decrease in MMSE scores (P=0.23) and an increased risk of MCI (odds ratio=1.95, 95% CI 0.40–9.43) (Table 1). Thus, even though the sample size was small and the associations were not statistically significant, the results suggest that polypharmacy could be an important factor in cognitive decline. Other notable findings included the detrimental effects of male gender, CCI greater than 0 and the presence of the ApoE e4 allele on cognitive decline, although only the CCI reached statistical significance. Furthermore, hypertension (treated) was significantly associated with higher MMSE scores. These results were consistent with the analyses done for MCI and for change in MMSE scores over time. Table 1 Multivariable Models Results for the Effects of Polypharmacy on MMSE or MCI (N=439 Individuals) The sampled population was unusually healthy and educated compared with the general American population. The prevalences of diabetes, hypertension, and obesity in the studied sample (0.53%, 34.5% and 10.5%, respectively) were much lower than the 26.9%, 71.6% and 35% prevalences described for those diseases in Americans older than 65 years.4–5 According to the U.S. Department of Health and Human Services, the percentage of older people that completed high school rose from 28% to 71% between 1970 and 2003.6 Approximately 83% of the sample studied had completed a high school education, and taking into consideration that the recruitment process was between 1979 and 2003, it is possible to establish that this sample was unusually highly educated. These characteristics may limit the generalizability of these results to the American population. Anticholinergic drugs and other drugs categorized as potentially inappropriate medication (PIM) have been found to be strongly associated with cognitive impairment, whereas other categories of drugs have not shown an association.7 In addition, the more drugs the patient is receiving, the more likely it is to observe an adverse drug event, such as cognitive impairment.8–10 It was not possible to look at specific drug types or PIM use in this study, which are possible underlying mechanisms for this association; however, it would be important that future research takes into consideration that specific drugs can have a negative or positive impact on the cognitive performance of a subject, or not have any impact at all, which makes it even more important to incorporate the specific type of drugs in future research. Nevertheless, the results obtained suggest that it is important for health professionals to thoroughly evaluate medication use in the elderly and try to limit the number of medications (both prescription and over-the-counter), not only to avoid possible adverse drug reactions and interactions but also to achieve a good treatment compliance.

Androgens, Bilateral Oophorectomy, and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures.

OBJECTIVE Diabetes elevates cardiovascular disease (CVD) risk more markedly in women than in men. Because the high risk of CVD among women with type 2 diabetes (DM2) may be partly due to increased ovarian androgen production, we investigated whether a history of bilateral salpingo oophorectomy (BSO) is inversely associated with CVD mortality among women with DM2. RESEARCH DESIGN AND METHODS Data were obtained from 7,977 women (a random subset of 564 had measurements of sex-steroid hormones) enrolled in the Study of Osteoporotic Fractures (SOF), a community-based, multicenter study that monitored women aged ≥65 years for a mean of 15.1 years. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. RESULTS The average age at baseline was 71.5 years, with 6.3% and 18% of participants reporting a history of diabetes or BSO, respectively. In the subset of the SOF cohort with sex-steroid hormone measurements, those with DM2 had 43.6% significantly higher levels of free testosterone that were partly explained by age and adiposity, whereas total and free testosterone levels were lower in women with BSO than in those with intact ovaries. CVD mortality was elevated in women with DM2 without BSO (HR 1.95, 95% CI 1.62–2.35) as well as in women with DM2 and BSO (HR 2.56, 95% CI 1.79–3.65; P = 0.190 for interaction). Overall, BSO was not associated with CVD mortality (HR 1.05, 95% CI 0.89–1.23). CONCLUSIONS The association of diabetes with CVD was not reduced by BSO, suggesting that ovarian hyperandrogenemia may not be a primary mechanism to explain the high risk for CVD among women with DM2.