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Rationale: Approximately 40% of people worldwide are exposed to household air pollution (HAP) from the burning of biomass fuels. Previous efforts to document health benefits of HAP mitigation have been stymied by an inability to lower emissions to target levels. Objectives: We sought to determine if a household air pollution intervention with liquefied petroleum gas (LPG) improved cardiopulmonary health outcomes in adult women living in a resource-poor setting in Peru. Methods: We conducted a randomized controlled field trial in 180 women aged 25–64 years living in rural Puno, Peru. Intervention women received an LPG stove, continuous fuel delivery for 1 year, education, and behavioral messaging, whereas control women were asked to continue their usual cooking practices. We assessed for stove use adherence using temperature loggers installed in both LPG and biomass stoves of intervention households. Measurements and Main Results: We measured blood pressure, peak expiratory flow (PEF), and respiratory symptoms using the St. George’s Respiratory Questionnaire at baseline and at 3–4 visits after randomization. Intervention women used their LPG stove exclusively for 98% of days. We did not find differences in average postrandomization systolic blood pressure (intervention – control 0.7 mm Hg; 95% confidence interval, −2.1 to 3.4), diastolic blood pressure (0.3 mm Hg; −1.5 to 2.0), prebronchodilator peak expiratory flow/height(2) (0.14 L/s/m(2); −0.02 to 0.29), postbronchodilator peak expiratory flow/height(2) (0.11 L/s/m(2); −0.05 to 0.27), or St. George’s Respiratory Questionnaire total score (−1.4; −3.9 to 1.2) over 1 year in intention-to-treat analysis. There were no reported harms related to the intervention. Conclusions: We did not find evidence of a difference in blood pressure, lung function, or respiratory symptoms during the year-long intervention with LPG. Clinical trial registered with www.clinicaltrials.gov (NCT02994680).

Objectives: To determine the effect of statins on cognitive decline in healthy elderly adults. Design: Longitudinal. Setting: National Institute of Aging network of Alzheimer's Disease Centers. Participants: Research volunteers with normal cognition at baseline evaluated an average 4.1 times over 3.4 years (1,244 statin users, 2,363 nonusers) and with mild cognitive impairment (MCI) at baseline evaluated an average 3.9 times over 2.8 years (763 users, 917 nonusers). Measurements: Cognitive performance was assessed according to 10 neuropsychological indices and the Clinical Dementia Rating Sum of Boxes (CDR-SOB). Repeated-measures analyses adjusted for age, sex, education, comorbidities, and family history of dementia were conducted. Results: Of participants with normal cognition at baseline, statin users performed significantly better across all visits in attention (Trails A) and had significantly slower annual worsening in CDR-SOB scores (P = .006) and slower worsening in Mini-Mental State Examination scores than nonusers (which was not significant after adjusting for multiple comparisons, P = .05). For participants with MCI, statin users performed significantly better across all visits on attention measures (Trail-Making Test Part A), verbal skills (Category Fluency), and executive functioning (Trail-Making Test Part B, Digit Symbol, and Digits Backward), but there were no differences in cognitive decline between users and nonusers. Conclusion: Elderly adults with normal cognition at baseline who used statins had a slower rate of annual worsening in CDR-SOB than nonusers.

There is controversy as to whether hypertension is a risk factor for cognitive impairment and decline, with some studies finding a positive association1–7 and others not.8–12 recent evidence-based review13 of published studies conducted by an expert panel under the auspices of the National Institutes of Health (NIH) concluded that the evidence of such an association is weak, in part because of the heterogeneity in definitions of mild cognitive impairment (MCI) and hypertension and differences in hypertension ascertainment methods (e.g., measured blood pressure (BP) vs reliance on self-report). In the United States, nearly 70% of persons aged 60 and older have hypertension,14 and it is estimated that 15 million to 18 million persons in this age group will develop dementia by 2050.15 Therefore, determining whether an association exists between high BP and cognitive function is important for targeting potential neuroprotective strategies. The results of clinical drug trials with antihypertensive agents have been mixed concerning their efficacy in preventing cognitive decline and dementia onset,13,16 although encouraging findings are available from a recent clinical trial employing lifestyle changes. One study17 found that prehypertensive and hypertensive adults receiving treatment with diet and aerobic exercise over a 4-month period showed greater improvements in executive functioning, memory, and psychomotor speed than those exposed to a diet intervention alone or a placebo condition of standard care. Systolic and diastolic BP decreased significantly over the study period for the intervention group but not the control group. The current study examined whether there is an association between high BP and decline in cognitive status in individuals with MCI over a 2-year period. The importance of the effect of adequate BP control on cognitive performance was demonstrated in a cross-sectional study of communityresiding older adults.18 Irrespective of a prior diagnosis of hypertension, persons with high BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) at the time of neuropsychological testing performed worse than normotensive individuals on measures of visual memory, motor speed, and visuomotor integration. Persons with a prior diagnosis and high BP levels were most vulnerable to poor performance. BP levels were examined at annual follow-up visits, rather than at a single baseline visit, to determine whether BP was routinely normotensive or high and whether this, in turn, affected the trajectory of cognitive changes. Rather than a single measure of overall cognitive status, participants in the current study underwent multiple tests examining attention, memory, language, and executive functioning. In older adults without dementia and those with MCI and Alzheimer's disease, hypertension is associated with a cognitive phenotype characterized by poorer attention and executive functioning and slower processing speed.10,19–25 Thus, it was expected that these same areas would be most sensitive to the chronic effects of high BP. Information was collected as part of the Uniform Data Set (UDS), a standardized assessment and data protocol maintained by the National Alzheimer's Coordinating Center, with 31 participating NIH, National Institute on Aging (NIA) Alzheimer's Disease Centers (ADCs) nationwide.26,27 It was hypothesized that individuals with MCI with high BP readings, according to published guidelines for hypertension,28 on more than one occasion would exhibit faster overall cognitive decline than those with normotensive levels on all occasions, with greater vulnerability of attention, executive functioning, and speeded performance.

Inappropriate methods are frequently used to calculate the population attributable fraction (AF) for a given exposure of interest. This commonly occurs when authors use adjusted relative risks (RRs) reported in the literature (the "source" data), without access to the original data. In this analysis, we examine the relationship between the direction and magnitude of confounding in the source data and resulting bias in the attributable fraction when incorrect methods are used. We assess confounding by the confounding risk ratio, which is the ratio of the crude RR to the adjusted RR. We assess bias in the AF by the ratio of the incorrectly calculated AF to the correctly calculated AF. Using generated data, we examine the relationship between confounding and AF bias under various scenarios of population prevalence of exposure and strength of the exposure-disease association. For confounding risk ratios greater than 1.0 (ie, crude RR >adjusted RR), the AF is underestimated; for confounding risk ratios less than 1.0 (ie, crude RR

Objective To test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson9s disease (PD). Methods 499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical non-motor and genetic. Results FOG and PIF were both associated with greater gait subscores and lower tremor subscores on the Unified Parkinson9s Disease Rating Scale (p≤0.02). However, they differed with regard to demographic, non-motor and genetic predictors. FOG was associated with greater duration of disease, with ORs of 3.01 (95% CI 1.35 to 6.72) and 4.91 (95% CI 2.29 to 10.54) for third and fourth quartiles of duration, respectively, versus the lowest half of duration. The risk of having psychotic symptoms was also significantly increased (OR 3.02, 95% CI 1.41 to 6.49; p=0.004). FOG was inversely associated with the presence of the CYP2D6 *4 allele (OR 0.41, 95% CI 0.21 to 0.80; p=0.009) suggesting a protective effect. PIF was associated with depression (OR 1.08, 95% CI 1.01 to 1.15; p APOE ɛ4 (OR 0.21, 95% CI 0.05 to 0.87; p=0.03), again suggesting a protective effect. Conclusion FOG and PIF have different demographic, non-motor and genetic predictors suggesting that they may be pathophysiologically distinct subtypes of PIGD. These findings have implications in the discovery of therapeutic targets for these disabling features as well as for predicting outcomes of PD.

Background The C8 Health Project was created, authorized, and funded as part of the settlement agreement reached in the case of Jack W. Leach, et al. v. E.I. du Pont de Nemours & Company (no. 01-C-608 W.Va., Wood County Circuit Court, filed 10 April 2002). The settlement stemmed from the perfluorooctanoic acid (PFOA, or C8) contamination of drinking water in six water districts in two states near the DuPont Washington Works facility near Parkersburg, West Virginia. Objectives This study reports on the methods and results from the C8 Health Project, a population study created to gather data that would allow class members to know their own PFOA levels and permit subsequent epidemiologic investigations. Methods Final study participation was 69,030, enrolled over a 13-month period in 2005-2006. Extensive data were collected, including demographic data, medical diagnoses (both self-report and medical records review), clinical laboratory testing, and determination of serum concentrations of 10 perfluorocarbons (PFCs). Here we describe the processes used to collect, validate, and store these health data. We also describe survey participants and their serum PFC levels. Results The population geometric mean for serum PFOA was 32.91 ng/mL, 500% higher than previously reported for a representative American population. Serum concentrations for perfluorohexane sulfonate and perfluorononanoic acid were elevated 39% and 73% respectively, whereas perfluorooctanesulfonate was present at levels similar to those in the U.S. population. Conclusions This largest known population study of community PFC exposure permits new evaluations of associations between PFOA, in particular, and a range of health parameters. These will contribute to understanding of the biology of PFC exposure. The C8 Health Project also represents an unprecedented effort to gather basic data on an exposed population; its achievements and limitations can inform future legal settlements for populations exposed to environmental contaminants.

This case-control study examined the potential for a common etiology of Parkinson's disease (PD) and Alzheimer's disease (AD) using reported family history. Structured interviews were used to collect AD and PD family history from subjects (n = 1,531) with AD, PD, AD/PD, or controls. Intergroup analysis compared reported AD and PD family histories in the three case groups to the histories reported in the control group. Intragroup analysis stratified each diagnostic group based on positive family history of AD, then compared the subgroups for a family history of PD. Subjects with AD had a higher risk of having a family history of AD [odds ratio (OR) 2.3; 1.5-3.4] and subjects with PD had a higher risk of having a family history of PD (OR 2.2; 1.2-4.0) as compared to control subjects. Intergroup analyses revealed no significant crossed risk, increased risk of subjects with AD having a family history of PD vs controls and vice versa. Intragroup analysis found that subjects with PD and a family history of AD were more likely to have a family history of PD (OR 1.7; 1.1-2.6) when compared to subjects with PD and no family history of AD. A similar trend was found for subjects with AD (OR 1.7; 0.9-3.1). AD and PD cases each have an increased familial risk of their respective disease. Probands with AD or PD and a family history of either disease have a higher crossed risk of a family history of the other disease. These findings suggest the existence of common genetic and/or environmental factors that predispose to both AD and PD in the subset of cases with positive family history of both neurodegenerative diseases.

Antihypertensives that modulate the renin-angiotensin system (RAS) on AD conversion in those with MCI has not been explored. Evidence suggests that blood-brain-barrier (BBB) permeability is necessary for these effects. We assessed the impact of RAS modulation on conversion to AD and cognitive decline in those with MCI, and the impact of BBB permeability and race on these associations. We analyzed data from the National Alzheimer’s Coordinating Center from the NIA-funded Alzheimer’s Disease Centers. We included individuals receiving antihypertensives with MCI at baseline and who had cognitive assessments on at least 2 follow-up visits. Outcomes included conversion to AD and cognitive and functional decline. Of 784 participants (M=75 years, 48% men), 488 were receiving RAS medications. RAS users were less likely to convert to AD (33% vs 40%; p=0.04) and demonstrated slower decline on the Clinical Dementia Rating sum-of-boxes (CDR-SOB, p

In 1997 the International Agency for Research on Cancer (IARC) classified 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD; the most potent dioxin congener) as a group 1 carcinogen based on limited evidence in humans, sufficient evidence in experimental animals, and extensive mechanistic information indicating that TCDD acts through a mechanism involving the aryl hydrocarbon receptor (AhR), which is present in both humans and animals. The judgment of limited evidence in humans was based primarily on an elevation of all cancers combined in four industrial cohorts. The group 1 classification has been somewhat controversial and has been challenged in the literature in recent years. In this article we review the epidemiologic and mechanistic evidence that has emerged since 1997. New epidemiologic evidence consists primarily of positive exposure–response analyses in several of the industrial cohorts, as well as evidence of excesses of several specific cancers in the Seveso accident cohort. There are also new data regarding how the AhR functions in mediating the carcinogenic response to TCDD. The new evidence generally supports the 1997 IARC classification.

Our aim was to examine disease-related and genetic correlates of the development of psychotic symptoms in a large population of patients with Parkinson's disease. We studied 500 patients with Parkinson's disease from the NeuroGenetics Research Consortium using logistic regression models. Predictors were demographic, clinical (motor/nonmotor features), and genetic, measured as continuous or dichotomous variables. Continuous measures were divided into population-based tertiles. Results are given as odds ratios (95% confidence intervals) for dichotomous variables and by ascending tertile for continuous variables. Psychotic symptoms were associated with increasing age: 4.86 (1.62-14.30) and 6.25 (2.09-18.74) (test for trend: P = 0.01); and duration of disease: 3.81 (1.23-11.76) and 5.33 (1.68-16.89) (test for trend: P = 0.03). For nonmotor features, we demonstrated positive trends with depression: 1.31 (0.47-3.61) and 5.01 (2.04-12.33) (test for trend: P0.0001); cognitive dysfunction: 0.69 (0.26-1.84) and 2.51 (1.00-6.29) (test for trend: P = 0.03); and an excess for those with sleep disorders: 2.00 (1.03-3.89) (P = 0.04). Psychotic symptoms were not associated with tremor or postural instability scores, but there was an association with freezing of gait: 3.83 (1.67-8.75) (P0.002). Psychotic symptoms were not associated with the presence of any examined polymorphisms in the apolipoprotein, alpha-synuclein, or microtubule associated protein tau genes. This is the largest study to examine correlates of psychotic symptoms in Parkinson's disease. We discovered a novel association with freezing of gait. We demonstrated an association with depression and duration of disease, both of which were inconsistently related in previous studies, and confirmed the association with age, cognitive dysfunction, and sleep disorders.

The life expectancy of persons cycling through the prison system is unknown. The authors sought to determine the 15.5-year survival of 23,510 persons imprisoned in the state of Georgia on June 30, 1991. After linking prison and mortality records, they calculated standardized mortality ratios (SMRs). The cohort experienced 2,650 deaths during follow-up, which were 799 more than expected (SMR = 1.43, 95% confidence interval (CI): 1.38, 1.49). Mortality during incarceration was low (SMR = 0.85, 95% CI: 0.77, 0.94), while postrelease mortality was high (SMR = 1.54, 95% CI: 1.48, 1.61). SMRs varied by race, with black men exhibiting lower relative mortality than white men. Black men were the only demographic subgroup to experience significantly lower mortality while incarcerated (SMR = 0.66, 95% CI: 0.58, 0.76), while white men experienced elevated mortality while incarcerated (SMR = 1.28, 95% CI: 1.10, 1.48). Four causes of death (homicide, transportation, accidental poisoning, and suicide) accounted for 74% of the decreased mortality during incarceration, while 6 causes (human immunodeficiency virus infection, cancer, cirrhosis, homicide, transportation, and accidental poisoning) accounted for 62% of the excess mortality following release. Adjustment for compassionate releases eliminated the protective effect of incarceration on mortality. These results suggest that the low mortality inside prisons can be explained by the rarity of deaths unlikely to occur in the context of incarceration and compassionate releases of moribund patients.

Mild cognitive impairment (MCI) often presages development of Alzheimer’s disease (AD). We recently completed a cross-sectional study to test the hypothesis that a combination of a brief cognitive screening instrument (Mini-Cog) with a functional scale (Functional Activities Questionnaire; FAQ) would accurately identify individuals with MCI and undiagnosed dementia. The Mini-Cog consists of a clock drawing task and 3-item recall, and takes less than 5 minutes to administer. The FAQ is a 30-item questionnaire completed by an informant. In addition to the Mini-Cog and FAQ, a traditional cognitive test battery was administered, and two neurologists and a neuropsychologist determined a consensus diagnosis of Normal, MCI, or Dementia. A classification tree algorithm was used to pick optimal cutpoints, and, using these cutpoints, the combined Mini-Cog and FAQ (MC-FAQ) predicted the consensus diagnosis with an accuracy of 83% and a weighted kappa of 0.81. When the population was divided into Normal and Abnormal, the sensitivity, specificity and positive predictive value were 89%, 90%, and 95%, respectively. The MC-FAQ discriminates individuals with MCI from cognitively normal individuals and those with dementia, and its ease of administration makes it an attractive screening instrument to aid detection of cognitive impairment in the elderly.

Background Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality. Objectives To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort. Methods We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers. Results Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72–0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics. Conclusions We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.