Interaction of Stress, Lead Burden, and Age on Cognition in Older Men: The VA Normative Aging Study

Abstract

BackgroundLow-level exposure to lead and to chronic stress may independently influence cognition. However, the modifying potential of psychosocial stress on the neurotoxicity of lead and their combined relationship to aging-associated decline have not been fully examined.ObjectivesWe examined the cross-sectional interaction between stress and lead exposure on Mini-Mental State Examination (MMSE) scores among 811 participants in the Normative Aging Study, a cohort of older U.S. men.MethodsWe used two self-reported measures of stress appraisal—a self-report of stress related to their most severe problem and the Perceived Stress Scale (PSS). Indices of lead exposure were blood lead and bone (tibia and patella) lead.ResultsParticipants with higher self-reported stress had lower MMSE scores, which were adjusted for age, education, computer experience, English as a first language, smoking, and alcohol intake. In multivariable-adjusted tests for interaction, those with higher PSS scores had a 0.57-point lower (95% confidence interval, −0.90 to 0.24) MMSE score for a 2-fold increase in blood lead than did those with lower PSS scores. In addition, the combination of high PSS scores and high blood lead categories on one or both was associated with a 0.05–0.08 reduction on the MMSE for each year of age compared with those with low PSS score and blood lead level (p < 0.05).ConclusionsPsychological stress had an independent inverse association with cognition and also modified the relationship between lead exposure and cognitive performance among older men. Furthermore, high stress and lead together modified the association between age and cognition.

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

“…The above mentioned may also mediate the early neuropsychiatric and behavioral alterations noted in AD. Further, psychological stress has an inverse association with cognition [84].…”

Infantile postnatal exposure to lead (Pb) enhances tau expression in the cerebral cortex of aged mice: Relevance to AD

“…Cognitive decline is an intermediate stage towards the development of AD. The Normative Aging Study (NAS) is a prospective longitudinal study that the Veterans Administration started in 1963 to monitor the effect of aging on different health conditions (Peters et al, 2010) with sub-groups of population investigated for a link between past non-occupational Pb exposure and cognitive decline. Participants in NAS were examined by several investigators, with different cognitive tests, sample size and time periods, who reported that higher levels of Pb in blood and/or bone were accompanied by poor cognitive performance in different cognitive tests including Wechsler Adult Intelligence Scale-Revised (WAIS-R), Consortium to Establish a Registry for AD (CERAD) and Mini-Mental state examination (MMSE) (Payton et al, 1998, Wright et al, 2003, Weisskopf et al, 2004, Weisskopf et al, 2007).…”

Sex-dependent and non-monotonic enhancement and unmasking of methylmercury neurotoxicity by prenatal stress

“…For these reasons, the study focused on brain monoamine systems and behaviors known to be impacted by MeHg (Ceccatelli et al, 2013; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2013; Newland et al, 2004; Onishchenko et al, 2007; Peters et al, 2010; Yoshida et al, 2011) and/or mediated by brain monoamine systems (Carratu et al, 2006; Castoldi et al, 2006; Coccini et al, 2011; Farina et al, 2011). First, multiple examples of the effects of MeHg effects that were enhanced by PS, or occurring only under conditions of PS, i.e., being unmasked by PS, were observed, including changes in brain neurochemistry and in behavior, particularly in females.…”

“…In some, but not all (Davidson et al, 2011) cohorts of children, prenatal MeHg in children has been associated with neurocognitive deficits, including increased diagnosis of attention deficit hyperactivity disorder and attention-related behaviors (Boucher et al, 2012), impaired visual recognition memory (Oken et al, 2005; Sagiv et al, 2012), and cognition and IQ (intelligence quotient) reductions (Jedrychowski et al, 2007; Lederman et al, 2008; Oken et al, 2008). Experimental animal studies likewise show deficits resulting from prenatal MeHg exposures in corresponding behavioral domains including deficits in learning, discrimination/transition reversal and working memory, increased perseverative behavior and increased behaviors interpreted as anxiety (Ceccatelli et al, 2013; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2013; Newland et al, 2004; Onishchenko et al, 2007; Peters et al, 2010; Yoshida et al, 2011). …”