Mixture Effects of Polychlorinated Biphenyls (PCBs) and Three Organochlorine Pesticides on Cognitive Function in Mohawk Adults at Akwesasne.

The Mohawks at Akwesasne have been highly exposed to polychlorinated biphenyls (PCBs), via releases from three aluminum foundries located near the reserve. They are also exposed to organochlorine pesticides, namely hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex. Previous studies have demonstrated reduced cognition in relation to total PCBs, but the effects of the mixtures of different PCB congener groups, HCB, DDE, and mirex on cognitive function have not been studied. Therefore, cognitive performance for executive function, scored via the digit symbol substitution test (DSST), in Mohawk adults aged 17-79 years (n = 301), was assessed in relation to serum concentrations of low-chlorinated PCBs, high-chlorinated PCBs, total PCBs, HCB, DDE, and mirex. We used mixture models employing the quantile-based g-computation method. The mixture effects of low-chlorinated PCBs, high-chlorinated PCBs, HCB, DDE, and mirex were significantly associated with 4.01 DSST scores decrements in the oldest age group, 47-79 years old. There were important contributions to mixture effects from low-chlorinated PCBs, high-chlorinated PCBs, and total PCBs, with smaller contributions of HCB and DDE. Our findings indicate that exposures to both low- and high-chlorinated PCBs increase the risk of cognitive decline in older adults, while DDE and HCB have less effect.

A Pilot Study to Examine Psychological and Neuropsychological Outcomes and a Novel Detoxification Program for Gulf War Illness.

INTRODUCTION: Exposures to environmental toxins have been associated with severe health problems for approximately one-quarter of the nearly 700,000 U.S. soldiers who served in the Gulf War between the years 1990 and 1991. Gulf War illness still affects about 30% of Gulf War veterans (GWV), causing reduced psychological wellness and neuropsychological function. METHOD AND MATERIALS: This pilot study used a randomized wait-list control design to explore the feasibility and efficacy of a novel detoxification method for GWV exposed to toxicants such as pesticides, nerve gases, and pyridostigmine bromide. Our study included 32 GWV (67% male), with a mean age of 51 (range: 43-70, SD = 6.97), who participated in a 4- to 5-week treatment that was hypothesized to reduce the reported psychological and neuropsychological symptoms. Psychological measures used included tests given for the evaluation of neurocognitive function, including motor function for a dominant hand with the grooved pegboard test; verbal and visual immediate and delayed memory with the Wechsler Memory Scale III abbreviated subtests; executive function domains of attention, speed, and mental flexibility with trail making test parts A and B and Stroop color and word test. Psychological status was measured using the nine subscales of the Symptom Checklist-90-Revised. RESULTS: Primary outcomes included between-group differences in self-reported psychological measures and a neuropsychological battery at 7-day and 3-month assessments. Baseline comparison revealed improvements in 16 of 19 psychological and neuropsychological measures at 7-day assessment and that 13 remained stable at 3-month assessment. CONCLUSIONS: We conclude that the detoxification procedure provided improvement in psychological and cognitive function for GWV and that future study is warranted.

Evidence of an age-related threshold effect of polychlorinated biphenyls (PCBs) on neuropsychological functioning in a Native American population.

Polychlorinated biphenyls (PCBs) have been suspected for some time of having adverse effects on neuropsychological functioning in humans. While there is evidence of slowing of cognitive function in children associated with exposure to PCBs, the evidence of comparable effects on adults is far less well understood. We report here on the neuropsychological evaluation of 277 Native American adults, ranging in age from 18 to 79, who were exposed to PCBs by way of environmental contamination in the St. Lawrence region of upstate New York. PCB body burden was estimated by 101 PCB congeners and neuropsychological functioning was assessed by a battery of 18 tests. Spline regression models were fitted to the latent variables of memory, motor function, and higher-order executive functioning. After adjusting for age, gender, and education the analyses revealed a threshold effect of PCBs at approximately 2 ppb. An age-by-PCB interaction effect was also observed for several variables which suggests that the threshold effect was largely confined to the age range of 40-79 and was not observable in the 18-40-year-old group. Implications of these results are discussed in comparison to previously published similar work with adults and in terms of its potential clinical meaningfulness.

Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population.

The major determinants of human polychlorinated biphenyl (PCB) body burden include the source and route of exposure and the toxicokinetic processes occurring after uptake. However, the relative importance of each factor for individual subjects cannot currently be determined. The present study characterizes levels and patterns of PCB congeners in a large cohort of adult Akwesasne Mohawks with historical PCB exposure. Total serum PCB ranged from 0.29 to 48.32 ng/g and was higher in adult men than in women (median of 3.81 vs. 2.94 ng/g). The mean serum congener profile for the full cohort was dominated by persistent penta- to hepta-chlorinated biphenyls; several labile congeners were also prominent. In order to provide additional information on individual body burden determinants, multivariate exploratory data analysis techniques were applied to the congener-specific serum PCB data. A self-training receptor model, polytopic vector analysis (PVA), was employed to determine the number, composition, and relative proportions of independent congener patterns that contributed to the overall serum PCB profile for each Mohawk subject. PVA identified five such patterns, each of which was characterized by a unique mix of congeners. One pattern observed in a limited number of Mohawks was similar to those reported for air sampled near contaminated sediment deposits at Akwesasne and for volatilized Aroclor 1248 and is hypothesized to reflect recent inhalation exposure in these subjects. A second pattern was consistent with unaltered Aroclor 1254. A third pattern, resembling Aroclor 1262 but without labile congeners, was correlated with age and is interpreted as representing a lifetime PCB accumulation profile. The final two patterns were dominated by subsets of major persistent congeners and are hypothesized to reflect intermediate bioaccumulation profiles and/or differences in individual toxicokinetics. The results confirm the utility of a multivariate exploratory analysis approach to congener-specific PCB data and provide additional insight into the exposure and individual factors that determine PCB body burden in this population.