Karen Bandeen-Roche

Environmental lead exposure and cognitive function in community-dwelling older adults

Objective: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. Methods: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with 109Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. Results: The mean (SD) blood lead level was 3.5 (2.2) μg/dL and tibia lead level was 18.7 (11.2) μg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-ε4, and testing technician (six domains p ≤ 0.01, one domain p ≤ 0.05). Blood lead was not associated with any cognitive domain. Associations with tibia lead were attenuated after adjustment for years of education, wealth, and race/ethnicity. Conclusions: Independent of recent lead dose, retained cumulative dose resulting from previous environmental exposures may have persistent effects on cognitive function. A portion of age-related decrements in cognitive function in this population may be associated with earlier lead exposure.

Measuring Systemic Inflammatory Regulation in Older Adults: Evidence and Utility

Aging is frequently accompanied by a proinflammatory state with adverse health consequences. This state is commonly assessed by markers in serum, either in isolation or ad hoc combination. We sought, alternatively, to develop scores summarizing multiple markers in accordance with biology on inflammatory regulation and evaluate their value added for discriminating functional outcomes in older adults. Data came from InCHIANTI (Invecchiare in Chianti; Aging in the Chianti Area) study participants age 65 years and older. Serum concentrations of seven inflammatory biomediators were subjected to latent variable analysis implementing a biological model of counterbalancing up- and down-regulation processes. Resulting process constructs were approximated by principal component scores; these, and individual markers, were evaluated as predictors of mobility impairment and frailty status in regression analyses, adjusting for key confounders. The biomediators interrelationships were well predicted by the hypothesized biology. The up-regulation score was independently associated with worsened mobility functioning and frailty risk. For mobility, the association was stronger than, persisted independently of, and accounted for association with each biomediator. The down regulation score was associated with frailty outcomes. We conclude that systemic inflammation is relevant to the process that leads to functional loss in older persons and can be validly measured through biologically informed summary of inflammatory markers.

Predictors of patterns of pain, fatigue, and insomnia during the first year after a cancer diagnosis in the elderly

Pain (P), fatigue (F), and insomnia (I) are among the most prevalent, distressing, and undermanaged symptoms experienced by cancer patients. Research has demonstrated that PFI co-occur; what remain unclear are the patterns and stability of PFI and the patient, disease, and treatment characteristics that predict PFI patterns over time. This secondary analysis used a data set composed of 867 elders (46% women) who were newly diagnosed with breast, colorectal, lung, or prostate cancer and followed at 4 points during the year after diagnosis. The universitys institutional review board approved this study. Descriptive statistics and multistate transition models using multinomial logistic regression were used. The typical participant was 72.6 years old, who reported 7.9 symptoms and 2.7 comorbidities. Previous PFI pattern was consistently associated with significantly increased risks of subsequent PFI pattern. At observations 1 to 3, lung cancer, treatment, higher comorbidity with breast cancer, and late-stage colorectal cancer were significantly associated with increased risks of PFI patterns. Advancing age was not significantly associated with increased risks of PFI patterns. Pain, fatigue, and insomnia co-occurrence declined over time but was associated with significantly increased risks of death or loss to follow-up and increased reports of other symptoms. Pain, fatigue, and insomnia co-occurrence is associated with adverse outcomes and should be proactively targeted for intervention.

Allostatic load and frailty in the women's health and aging studies.

Background: Frailty involves decrements in many physiologic systems, is prevalent in older ages, and is characterized by increased vulnerability to disability and mortality. It is yet unclear how this geriatric syndrome relates to a preclinical cumulative marker of multisystem dysregulation. The purpose of this study was to evaluate whether allostatic load (AL) was associated with the geriatric syndrome of frailty in older community-dwelling women. Methods: We examined the cross-sectional relationship between AL and a validated measure of frailty in the baseline examination of two complementary population-based cohort studies, the Womens Health and Aging studies (WHAS) I and II. This sample of 728 women had an age range of 70—79. We used ordinal logistic regression to estimate the relationship between AL and frailty controlling for covariates. Results: About 10% of women were frail and 46% were prefrail. AL ranged from 0 to 8 with 91% of participants scoring between 0 and 4. Regression models showed that a unit increase in the AL score was associated with increasing levels of frailty (OR = 1.16, 95% CI = 1.04—1.28) controlling for race, age, education, smoking status, and comorbidities. Conclusion: This study suggests that frailty is associated with AL. The observed relationship provides some support for the hypothesis that accumulation of physiological dysregulation may be related to the loss of reserve characterized by frailty.

Changes in Systolic Blood Pressure Associated With Lead in Blood and Bone

Background: Several studies have examined longitudinal associations of blood pressure change or hypertension incidence with lead concentration in blood or bone. It is not clear whether the observed associations reflect an immediate response to lead as a consequence of recent dose or rather are a persistent effect of cumulative dose over a lifetime. Methods: We followed 575 subjects in a lead-exposed occupational cohort in South Korea between October 1997 and June 2001. We used generalized estimating equation models to evaluate blood pressure change between study visits in relation to tibia lead concentrations at each prior visit and concurrent changes in blood lead. The modeling strategy summarized the longitudinal association of blood pressure with cumulative lead dose or changes in recent lead dose. Results: On average, participants were 41 years old at baseline and had worked 8.5 years in lead-exposed jobs. At baseline, the average ± standard deviation for blood lead was 31.4 ± 14.2 μg/dL, and for tibia lead, it was 38.4 ± 42.9 μg/g bone mineral. Change in systolic blood pressure during the study was associated with concurrent blood lead change, with an average annual increase of 0.9 (95% confidence interval = 0.1 to 1.6) mm Hg for every 10-μg/dL increase in blood lead per year. Conclusion: The findings in this relatively young population of current and former lead workers suggest that systolic blood pressure responds to lead dose through acute pathways in addition to the effects of cumulative injury.

Sex differences in cognition in healthy elderly individuals

ABSTRACT Sex differences in patterns of cognitive test performance have been attributed to factors, such as sex hormones or sexual dimorphisms in brain structure, that change with normal aging. The current study examined sex differences in patterns of cognitive test performance in healthy elderly individuals. Cognitive test scores of 957 men and women (age 67–89), matched for overall level of cognitive test performance, age, education, and depression scale score, were compared. Men and women were indistinguishable on tests of auditory divided attention, category fluency, and executive functioning. In contrast, women performed better than men on tests of psychomotor speed and verbal learning and memory, whereas men outperformed women on tests of visuoconstruction and visual perception. Our finding that the pattern of sex differences in cognition observed in young adults is observed in old age has implications for future studies of both healthy elderly individuals and of those with cognitive disorders.

Multimorbidity and Evidence Generation

Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice.

Surrogate screening models for the low physical activity criterion of frailty

Background and aims: Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women’s Health and Aging Study (WHAS). Methods: Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by “relative influence” in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Results: Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. Conclusions: We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

Predictors of Lane-Change Errors in Older Drivers

OBJECTIVES: To determine the factors that predict errors in executing proper lane changes among older drivers.

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

OBJECTIVESnWe sought to identify predictors of lead concentrations in the blood, tibias, and patellae of older adults and to describe differences by gender, race/ethnicity, and other factors that can influence lead toxicokinetics and, thus modify health effects.nnnMETHODSnParticipants aged 50 to 70 years (N=1140) were randomly identified from selected neighborhoods in Baltimore, Maryland. We measured lead concentrations by anodic stripping voltammetry (in blood) and (109)Cd-induced K-shell x-ray fluorescence (in bone). We used multiple linear regression to identify predictors of lead concentrations.nnnRESULTSnMean (SD) lead concentrations in blood, tibias, and patellae were 3.5 (2.4) mug/dL, 18.9 (12.5) mug/g, and 6.8 (18.1) mug/g, respectively. Tibia concentrations were 29% higher in African Americans than in Whites (P < .01). We observed effect modification by race/ethnicity on the association of gender and physical activity to blood lead concentrations and by gender on the association of age to tibia lead concentrations. Patella lead concentrations differed by gender; apolipoprotein E genotype modified this relation.nnnCONCLUSIONSnAfrican Americans evidenced a prominent disparity in lifetime lead dose. Women may be at higher risk of release of lead from bone and consequent health effects because of increased bone demineralization with aging.