Bone lead levels are associated with measures of memory impairment in older adults

Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.
NeuroToxicology (Impact Factor: 3.38). 05/2009; 30(4):572-80. DOI: 10.1016/j.neuro.2009.05.007
Source: PubMed


Accumulating evidence suggests a link between lead exposure and memory impairment but assessments based on predictive and validated measures are lacking. We conducted a pilot study of 47 healthy subjects 55-67 years of age to examine associations between bone lead levels and 4 tests sensitive to the natural history of Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). These include three subtests of the Cambridge Neuropsychological Test Automated Battery (delayed match-to-sample, paired associates learning and spatial recognition memory) and the Montreal Cognitive Assessment Test. Bone lead concentrations were measured at the mid-shaft of the tibia and the calcaneus with K X-ray fluorescence. Higher tibial and calcaneal bone lead values were significantly (p<0.05) associated with lower performance levels on delayed match-to-sample and paired associates learning in unadjusted analyses with Spearman rank correlation coefficients of about 0.4. Multiple linear regression analyses (i.e., least-squares means of cognitive test scores across tertiles of lead exposure) adjusted for age, education and smoking status continued to show an association of higher calcaneal lead levels with increasing memory impairments on delayed match-to-sample (p=0.07). As might be expected, additional adjustment for history of hypertension reduced the strength of this association (p=0.19). Given the demonstrated impact of lead exposure on hypertension and the vascular etiology of certain dementias, we speculate that hypertension could play a mediating role in the association between lead exposure and memory impairment.

Download full-text


Available from: James R. Campbell, Feb 03, 2016
  • Source
    • "As well as organic compounds, the scientific literature highlights the myriad adverse effects of various inorganic toxic elements such as mercury [25] [26] [27], aluminum [7] [8] [28], arsenic [8] [27] [29], copper [30] [31] [32] [33], and particularly lead [7] [34]. Elevated levels of lead have been implicated in hypertension and linked to vascular causes of memory impairment and dementia [35] [36]. The acquisition, storage, and retrieval of verbal information also appears to be affected by cumulative exposure to lead [37]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Juxtaposed alongside the ongoing rise in the incidence and prevalence of dementia, is the surge of recent research confirming widespread exposure and bioaccumulation of chemical toxicants. Evidence from sources such as the Centers for Disease Control reveals that most people have accrued varying degrees of assorted toxic pollutants including heavy metals, flame retardants, and pesticide residues within their bodies. It has been well established that many of these toxicants have neurodegenerative as well as neurodevelopmental impact as a result of various pathophysiologic mechanisms including neuronal mitochondrial toxicity and disruption of neurotransmitter regulation. Elimination of stockpiled toxicants from the body may diminish adverse toxicant impact on human biology and allow restoration of normal physiological function. Incorporating a review of medical literature on toxicant exposure and dementia with a case history of a lead-exposed individual diagnosed with dementia, this paper will discuss a much overlooked and potentially widespread cause of declining brain function and dementia.
    Full-text · Article · Feb 2015 · Behavioural neurology
  • Source
    • "Exposure to lead has been recognized as a major public health risk, particularly in developing countries (Flora et al., 2012). Recent investigations have established a link between lead contamination and memory impairment in humans (Sadiq et al., 2012; Wijngaarden et al., 2009). Lead exposure causes an increase in reactive oxygen species (Bondy & Guo, 1996; Patra et al., 2011) and alters nitrite and nitrate levels in rat brain (Chen et al., 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Bacopa monniera is a rejuvenating herb for brain cells enhancing learning and cognitive ability. In the present investigation, the ameliorative effects of Bacopa monniera were examined against lead-induced oxidative stress in different regions of rat brain. Male rats were divided into five groups: control (1000 ppm sodium acetate) and exposed (1000 ppm lead acetate) for 4 weeks; DMSA (Meso-2,3-Dimercaptosuccinic acid)-treated (90 mg/kg body weight/day); Bacopa monniera-treated (BM) (10 mg/kg body weight/day) and a combination of BM + DMSA for seven consecutive days after 4 weeks of lead exposure. After treatment, the whole brain was isolated by sacrificing rats and four regions were separated namely cerebellum, hippocampus, frontal cortex and brain stem. Results indicated a significant (p < 0.05) increase in reactive oxygen species (ROS), lipid peroxidation products (LPP) and total protein carbonyl content (TPCC) in association with tissue metal content in all the four regions of brain for exposed group compared with their respective controls. However, the lead-induced ROS, LPP, TPCC and tissue metal content were lowered on treatment with Bacopa monniera, almost reaching the control group values in all the above brain regions compared to DMSA and a combination therapy. Results suggest that Bacopa monniera can mitigate the lead induced-oxidative stress tissue specifically by pharmacologic interventions which encompass both chelation as well as antioxidant functions.
    Full-text · Article · Dec 2013 · Drug and Chemical Toxicology
  • Source
    • "Although blood lead (BPb) levels have dramatically decreased in the general population (Annest et al. 1983; Centers for Disease Control and Prevention 2009), lead (Pb) exposure remains an issue in specific population clusters, such as low socio economic inner-city neighborhoods (Haley and Talbot 2004), and in occupationally exposed workers. Pb is a well-known neuro toxicant (Shih et al. 2007; van Wijngaarden et al. 2009) but has also been linked to hyper tension in humans (Navas-Acien et al. 2007; Vaziri and Gonick 2008; Weaver et al. 2008) and to alterations in the hypothalamic–pituitary–adrenal (HPA) axis in animals. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic-pituitary-adrenal (HPA) axis function.Objective: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers. Seventy male participants completed the Trier Social Stress Test (TSST). Serum cortisol (CORT) and plasma adrenocorticotropic hormone (ACTH) were assessed in response to and during recovery from the stressor. We measured Pb in blood, a biomarker of recent exposure, and in tibia bone by X-ray fluorescence (XRF), a biomarker of chronic exposure. The TSST induced statistically significant increases in ACTH and CORT in the participants. At baseline, ACTH was not significantly higher (p = 0.052) in participants with higher blood Pb concentration, but CORT was significantly lower in these participants (p = 0.016). Adjusted linear regression models indicated a positive association between blood and bone Pb and the increase in ACTH in response to stress. However, Pb was not strongly associated with changes in CORT in response to stress. Pb was also associated with the ACTH:CORT ratio at baseline and throughout the course of the protocol, suggesting an adrenal hyporesponsiveness in participants with higher Pb concentrations. The altered HPA-axis stress response observed in participants exposed to higher levels of Pb further supports the idea that lead may contribute to a host of biological dysfunctions beyond the classical neurotoxic effects.
    Full-text · Article · Nov 2011 · Environmental Health Perspectives
Show more